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Emerging Issues:
Cancer in New Hamphsire
February 2008
New Hamphsire Comprehensive Cancer Collaboration
The mission of the Comprehensive Cancer Collaboration is to reduce significantly the
incidence of, suffering from, and mortality due to cancer for people in New Hampshire
through prevention, early detection, treatment, rehabilitation, and palliation. We will
accomplish this goal by means of an integrated and coordinated alliance of
stakeholders that will utilize available epidemiological data and evidence based
research to set priorities for action.
Development and publication of this report was supported by: the Centers for Disease
Control and Prevention, PA02060 under cooperative agreement number U55/CCU121912 , New Hampshire Division of Public Health Services(DPHS), New Hampshire
Comprehensive Cancer Control Program, NH Comprehensive Cancer Collaboration
and the Foundation for Healthy Communities.
Emerging Issues 1
EXECUTIVE SUMMARY ................................................................................................ 4
VISION ............................................................................................................................ 4
MISSION ......................................................................................................................... 4
EXECUTIVE SUMMARY ................................................................................................ 5
KEY TOPICS: AN OVERVIEW OF EMERGING ISSUES .............................................. 8
PART I: LITERATURE REVIEW WITHOUT ABSTRACTS ......................................... 13
SECTION A: PRIMARY PREVENTION ............................................................................ 14
Behavior ............................................................................................................................... 15
Tobacco Use ....................................................................................................................... 15
Exposure to Radiation ....................................................................................................... 18
Ionizing Radiation ........................................................................................................... 18
Ultraviolet Radiation ....................................................................................................... 18
Environmental Pollutants .................................................................................................. 20
General Exposure to Pollution ..................................................................................... 20
Arsenic ............................................................................................................................. 21
MtBE ................................................................................................................................. 24
Pesticides ........................................................................................................................ 25
Radon ............................................................................................................................... 27
Other Pollutants .............................................................................................................. 28
Diet and Nutrition................................................................................................................ 30
General ............................................................................................................................ 30
Breast Cancer, Diet, & Nutrition ................................................................................... 31
Colon Cancer, Diet, & Nutrition .................................................................................... 31
Prostate Cancer, Diet, & Nutrition ............................................................................... 33
Personal Care Products .................................................................................................... 36
SECTION B: PREVENTION AND EARLY DETECTION ................................................. 37
Healthcare Access ............................................................................................................. 38
Breast and Cervical Cancer.............................................................................................. 40
General ............................................................................................................................ 40
Cervical Cancer Prevention and Screening ............................................................... 40
Genetic Testing............................................................................................................... 41
Imaging ............................................................................................................................ 42
Prostate Cancer Screening .............................................................................................. 45
Colorectal Screening ......................................................................................................... 48
SECTION C: TREATMENT AND SURVIVORSHIP ........................................................ 50
Radiation and Chemotherapy .......................................................................................... 51
Surgery................................................................................................................................. 54
Alternative Therapies ......................................................................................................... 56
Other Emerging Issues in Cancer Treatment ................................................................ 57
SECTION D: PALLIATION ................................................................................................... 60
General ................................................................................................................................ 61
Pharmaceutical Palliation.................................................................................................. 62
Emotional, Spiritual, and Social Palliation ...................................................................... 64
Medical Marijuana .............................................................................................................. 65
PART II: LITERATURE REVIEW WITH ABSTRACTS ................................................ 66
Emerging Issues 2
SECTION A: PRIMARY PREVENTION ............................................................................ 67
Behavior ............................................................................................................................... 68
Tobacco Use ....................................................................................................................... 70
Exposure to Radiation ....................................................................................................... 81
Ionizing Radiation ........................................................................................................... 81
Ultraviolet Radiation ....................................................................................................... 83
Environmental Pollutants .................................................................................................. 89
General Exposure to Pollution ..................................................................................... 89
Arsenic ............................................................................................................................. 97
MtBE ............................................................................................................................... 108
Pesticides ...................................................................................................................... 116
Radon ............................................................................................................................. 127
Other Pollutants ............................................................................................................ 133
Diet and Nutrition.............................................................................................................. 136
General .......................................................................................................................... 136
Breast Cancer, Diet, & Nutrition ................................................................................. 140
Colon Cancer, Diet, & Nutrition .................................................................................. 142
Prostate Cancer, Diet, & Nutrition ............................................................................. 151
Personal Care Products .................................................................................................. 164
SECTION B: PREVENTION AND EARLY DETECTION ............................................... 169
Healthcare Access ........................................................................................................... 170
Breast and Cervical Cancer............................................................................................ 178
General .......................................................................................................................... 178
Cervical Cancer Prevention and Screening ............................................................. 180
Genetic Testing............................................................................................................. 187
Imaging .......................................................................................................................... 192
Prostate Cancer Screening ............................................................................................ 202
Colorectal Screening ....................................................................................................... 217
SECTION C: TREATMENT AND SURVIVORSHIP ...................................................... 224
Radiation and Chemotherapy ........................................................................................ 225
Surgery............................................................................................................................... 238
Alternative Therapies ....................................................................................................... 247
Other Emerging Issues in Cancer Treatment .............................................................. 253
SECTION D: PALLIATION ................................................................................................. 263
General .............................................................................................................................. 264
Pharmaceutical Palliation................................................................................................ 269
Emotional, Spiritual, and Social Palliation .................................................................... 277
Medical Marijuana ............................................................................................................ 280
PART III: LIST OF REFERENCES WITH ADDITIONAL CITATIONS ........................ 283
Emerging Issues 3
EXECUTIVE SUMMARY
VISION
The vision of the New Hampshire Comprehensive Cancer Collaboration is for cancer
incidence, morbidity, and mortality to be significantly reduced or eliminated and for the
people of New Hampshire to enjoy health and quality of life.
MISSION
The mission of the Comprehensive Cancer Collaboration is to reduce significantly the
incidence of, suffering from, and mortality due to cancer for people in New Hampshire
through prevention, early detection, treatment, rehabilitation, and palliation. We will
accomplish this goal by means of an integrated and coordinated alliance of
stakeholders that will utilize available epidemiological data and evidence based
research to set priorities for action.
Emerging Issues 4
EXECUTIVE SUMMARY
This report was prepared for the New Hampshire Comprehensive Cancer
Collaboration Emerging Issues in Cancer workgroup by the Plymouth State University
Center for Rural Partnerships in collaboration with researchers at Keene State College.
The purpose of the report is to detail emerging issues related to cancer, which can be
introduced to health care providers, policy makers, health care advocates, and the
general public in New Hampshire. The information in this literature review will also be
provided to the other New Hampshire Comprehensive Cancer Collaboration workgroups
to inform and help in the development of their education and media campaigns.
The World Health Organization Cancer Control Programme describes cancer’s
worldwide reach.
“Cancer affects everyone – the young and old, the rich and poor, men, women
and children – and represents a tremendous burden on patients, families and
societies… Yet, many of these deaths can be avoided. Over 40% of all cancers
can be prevented. Others can be detected early, treated and cured. Even with
late stage cancer, the suffering of patients can be relieved with good palliative
care (WHO 2006).”
Cancer is a generic term for a group of more than 100 diseases that affects all body
parts. What all cancers have in common is unrestrained cell growth and division
caused by damage to the genes regulating the cell division and repair cycle. This rapid
growth of abnormal cells can grow beyond their usual boundaries and invade adjoining
body parts. Cancer is caused by internal and external factors. Internal factors include
inherited mutations, hormones, immune conditions, and mutations caused by
metabolism, etc. External factors include tobacco, radiation, chemicals, or infectious
agents, etc. (ACS 2007). Much time may pass in-between exposure to an external
factor and detectable cancer, but it all starts with one abnormal cell (ACS 2007; WHO
2006). Research into all aspects of cancer is ever-growing causing an ever-growing
understanding of the disease.
Research into all aspects of cancer is ever-growing, causing an ever-growing
understanding of the disease. However, people want to know what is their risk of
getting cancer? Every person can develop cancer, but some people have varying risks
that decrease or increase this chance. Risk is a mathematical probability of something
occurring. Scientists calculate cancer risk estimates by studying large groups of people
to discover the probability that a person or category of people will develop cancer over a
certain time-period (Mayo Clinic 2007). According to the American Cancer Society
publication Cancer Facts & Figures- 2007 American men have a lifetime risk of slightly
less than 1 in 2 of developing cancer. The lifetime risk for an American woman
developing cancer is slightly more than 1 in 3. Lifetime risk is a term that describes
Emerging Issues 5
the probability that a person will develop or die from cancer over the course of a lifetime.
Lifetime risk is a type of absolute risk- the actual numeric chance or probability of
developing cancer during a specified time period. There is another type of calculated
cancer risk- relative risk. Relative risk is a comparison of a certain risk factor and the
people exposed to that specific risk factor. Relative risk looks at the strength of
relationship between a risk factor and the heightened or lessened chance of cancer
(ACS 2007; Mayo Clinic 2007).
In 2005, New Hampshire Comprehensive Cancer Collaboration (NHCCC)
released its plan, Cancer in New Hampshire: A Call to Action 2010. The first priority is
to ensure that it not just be a report on cancer but “function as a clearly defined action
plan to reduce the incidence, morbidity and mortality of cancer.” Incorporated into the
NHCCC plan in the spring of 2005, the Emerging Issues (EI) workgroup was charged
with the goal of identifying emerging issues in cancer in New Hampshire and developing
an action plan that will benefit New Hampshire residents and health care providers.
Towards that aim, the EI workgroup identified a priority objective to increase public and
provider awareness regarding emerging issues in cancer in New Hampshire. The EI
workgroup proposes to achieve that goal in two phases. This report comprises part of
Phase One.
Phase One of the EI workgroup action plan includes a strategy to identify existing
national and local resources that contain evidence-based research on emerging issues
in the following areas: primary prevention, early detection, treatment, survivorship, and
palliation; environmental factors that may lead to cancer; and emerging studies and
data relevant to New Hampshire residents and providers. Phase Two will include a plan
for the dissemination of “emerging issues” information in order to increase awareness of
the public and providers, with a specific emphasis on prevention and environmental
factors relevant to New Hampshire residents and providers.
This report is intended to inspire additional conversation and research on the
emerging issues in cancer. The authors hope that the report will become a “living
document” that will grow and develop with more input. In its current form, it is
comprised of a literature review, internet-based research, and correspondence with
scientists and health care providers. Students at Plymouth State University and Keene
State College1 conducted research for this report with oversight by the director of the
Plymouth State University Center for Rural Partnerships.
Emerging issues include new scientific discoveries, new developments in health
care, and topics of renewed public interest. Data collection for this document proved
challenging in that many scientists and health care providers were unable to provide
information about the latest emerging issues for identifiable reasons. Therefore, not all
emerging issues in New Hampshire are included. In some instances, scientists were
1
Stacy Luke and Casey Doyle at Plymouth State University and Jaime Ingalls at Keene State College conducted this
research. Stacy Luke was the project leader with support and oversight from Thaddeus Guldbrandsen, Director of
the Center for Rural Partnerships at Plymouth State University. Work was done in dialogue with the NHCCC EI
Workgroup, especially Laura Holmes and Martha Hill.
Emerging Issues 6
unable to report on emerging issues prior to undergoing a rigorous peer review process
and publication. Some information was proprietary in nature, and researchers were
unwilling to report it to the authors of this report. Finally, busy schedules of scientists
and health care providers made it challenging to collect information within a specified
time frame. Once this report is made public, the authors hope that additional
information will be forthcoming.
For the most part, emerging issues in New Hampshire are the same as those in
the rest of the country, with some exceptions. There are a few differences due to our
geography, rural areas, cultural make-up, and geology. For example, because of the
state’s unique geology, radon and arsenic can pose significant cancer hazards for New
Hampshire residents. The uneven distribution of health care providers, hospitals, and
palliative care providers within the state also impacts outcomes associated with cancer
and its treatment. Social inequality and poverty pose challenges for cancer diagnosis
and treatment in New Hampshire, as it does elsewhere in the United States. Finally,
because many of the state’s employers are small businesses, access to health
insurance is a particular concern for the population.
This document focuses on the predominant forms of cancer in New Hampshire;
therefore, information on certain types of cancer, such as leukemia and brain cancer,
are underrepresented.
Emerging Issues 7
KEY TOPICS: AN OVERVIEW OF EMERGING ISSUES
This section highlights prominent emerging issues noted in the literature review
and conversations with scientists and health professionals.
Tobacco Use
The negative health impacts of tobacco use are well established; however,
current research focuses on the effects of tobacco advertising, behavioral counseling,
and the methods best used to reduce smoking (smoking bans, smoking cessation
programs, etc.). This section of the literature review focuses on emerging issues
regarding the effects of advertising on tobacco use and the methodology used in
smoking cessation programming and behavior counseling.
The types of advertising researched include those made by smoking companies
as well as public service announcements geared toward reducing tobacco use. In the
studies cited, advertising of tobacco products was found to have a direct effect on teens’
use of tobacco products and that reducing the exposure to tobacco product advertising
reduces the number of young smokers. These studies recommend that restrictions on
tobacco advertising be increased, and tobacco-warning labels be made more effective.
Studies also indicate that one-on-one behavior counseling with numerous
meeting points over a sustained time period are extremely beneficial in helping mothers
reduce their smoking, and therefore, the exposure of Environmental Tobacco Smoke
(ETS) to their children.
Exposure to Radiation
Studies show that radiation is both a cause of and treatment for cancer. Ionizing
radiation has recently been linked as a cause of several cancers, including childhood
leukemia, breast cancer, and skin cancer (Belson et al. 2007; Cardis et al. 2007; Lichter
et al. 2000). As the effects of therapeutic ionizing radiation become better known, the
role of ionizing radiation in cancer screening is inevitably affected. New screening tools
are sought, such as ultrasound for breast cancer screening. Scientific studies have
shown that ultraviolet radiation is a well-known cause of skin cancer though the exact
role on the human body is still incompletely known. Emerging issues related to
ultraviolet radiation include gene-environment interactions related to skin cancer
susceptibility, peoples’ behaviors regarding sun safety, and the possible therapeutic role
it plays in reducing the risk of non-Hodgkin’s Lymphoma, breast, colon, ovary, and
prostate cancers.
A study of the Portsmouth Naval Shipyard indicates that there has been a
connection to higher levels of exposure to ionizing radiation and an increase in leukemia
Emerging Issues 8
cases (Yiin et al. 2005). However, researchers conclude that more research needs to be
conducted to definitively conclude the findings because of the small population size of
the study. Therapeutic radiation has been connected to an increased risk for
developing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
Studies indicate that education programs about proper skin protection against
ultraviolet radiation (UV) exposure have been beneficial in improving the skin protection
habits of individuals. In addition, providing multiple points of contact for education
reinforcement has been found to be most effective (Olsen et al. 2007).
Cumulative Exposure to Pollutants
Growing evidence shows that the human body is exposed to numerous toxicants
at low levels. Though each individual pollutant is encountered at assumingly “safe”
levels, the cumulative effects of many pollutants may cause numerous diseases,
including cancer. Citations include the environmental pollutants arsenic, radon, MtBE,
pesticides, dioxins, coal tar, and more. An additional source of cumulative exposure
may also include the chemical ingredients in some personal care products. Our
research also indicates that human biomonitoring is a growing field by the Centers for
Disease Control and Prevention (2001, 2003, 2005) and others such as Angerer et al.
(2007) that is being used to detect and track cumulative exposure to pollutants.
Arsenic
There is current and on-going research regarding arsenic in drinking water. The
United States Geological Survey (USGS) is working to document areas where high
levels are present (Ayotte et al. 2006). This research concludes that the use of well
water from private sources may correlate with excess bladder cancer mortality in New
England. Analytical studies are underway to clarify the relation between suspected
water contaminants, particularly arsenic, and raised bladder cancer rates in northern
New England. Ayotte et al. (2006b) also created a model to predict the probability of
arsenic levels beyond the recommended levels.
MtBE
The United States Geological Survey (USGS) is mapping areas with high levels
of MtBE. Whether or not MtBE is a carcinogen is not yet clear. The research on MtBE
in the state is not tied to any health effects. Current focus is on mapping the
occurrences of MtBE in public and private wells in New Hampshire. A study for
Rockingham County is completed (Ayotte et al. 2005), while another statewide study is
currently undergoing peer review (Ayotte, pers. comm.).
Emerging Issues 9
Air Quality
There is significant research on the dangers of occupational and environmental
exposures to a variety of airborne contaminants (radon, particulate matter, arsenic), in
addition to smoking, that may have a connection to lung cancer. Some of the most
important emerging and ongoing concerns for exposure in New Hampshire are indoor
radon levels, outdoor ambient air particulate matter (PM) concentrations, and exposure
to cigarette smoke. The studies cited in this report indicate that there is a need for
increased education about indoor radon exposure risks for homeowners in particular.
Studies also show that PM exposures of size cut less than or equal to 2.5 microns
comprised of metals and other volatile organic compounds are gaining the attention of
regulators nationwide; however, the need for more analytical data has been stated.
Research at Keene State College identifies diesel exhaust as a possible factor in lung
cancer in occupational settings and possibly for the general population.
Diet and Nutrition
Scientific debates about the role of nutrition in cancer risk and prevention are ongoing. There are several citations on the benefits of a Mediterranean diet on cancer
prevention. There are new studies on Vitamin D deficiency and cancer (Grant 2006;
Giovannucci et al. 2006; Meyer 2004; Schwartz and Skinner 2007). According to
Giovannucci & Michaud (2007), metabolic disruptions caused by obesity increase
occurrences of certain cancers such as colon, prostate, and pancreatic cancer. Obesity
may also reduce the effectiveness of treatment (Stroup et al. 2007; Dignam et al. 2006;
Pierce et al. 2007).
Healthcare Access
In the interviews conducted with health care providers for this review, equitable
access to high-quality health care was identified as a recurring theme. Interviewees
believed that before cancer incidence and deaths can be reduced, New Hampshire
residents must have access to healthcare for preventative education, screening, and, if
needed, treatment. The literature review indicates that there are many barriers to
healthcare access in New Hampshire: cost, insurance, distance, personal beliefs, and
disparities due to gender, race, ethnicity, primary language spoken, or socio-economic
status.
Cancer Prevention And Screening
Information on cancer prevention was not readily available on all kinds of
cancers. In the case of colorectal cancer, there was information on screening, which
remains a significant concern. Emerging issues in colorectal screening include issues
found in other cancer screening programs: risk assessment, genetic testing, patienthealth care provider communication, access to health care, social disparities, and
Emerging Issues 10
cultural beliefs. Citations found in this section discuss these issues and areas of
improvement.
Currently, there are no evidence-based guidelines for colorectal screening
(Marcella et al. 2007). The other topic of interest in screening has been about prostate
cancer, The symptoms and signs of prostate cancer usually manifest after it is too late
to 'cure' the condition, making screening for the cancer essential to reduce prostate
cancer deaths (Frydenberg & Wijesinha 2007). Screening usually takes two forms:
prostate specific antigen (PSA) and digital rectal examination. Many barriers exist to
screening, particularly cultural beliefs, patient-health care provider communication, and
perceived risk. Citations in this section address these barriers and others with
discussions on improving prostate screening for all men.
Cancer Treatment
Emerging issues in cancer treatment include targeted therapies aimed at the
biochemical pathways or gene interactions in the development of cancer. Early studies
of targeted cancer treatments show promising results. With these studies, researchers
are led to believe that generalized treatment for the body part the cancer is affecting
may be replaced by a treatment based on the molecular biology of the mutated cells.
Such studies include targeted treatment of non-small cell lung cancer (Zalcman et al.
2007), multiple myeloma (Anderson, 2007), and nucleotide-based targeted therapies for
prostate cancer (Sowery et al. 2007). Additional studies and clinical trials are
underway, such as the TailorX Trial, which is using molecular profiling to determine who
will benefit the most from chemotherapy.
This review found that many patients struggle with the decision to use surgery,
chemotherapy, radiation, or other “traditional” treatments for cancer. Some patients are
choosing complementary therapies, in part or in whole, to treat their cancer. According
to studies cited, complementary/alternative therapies are becoming increasingly popular
and research into their use, their effectiveness, and their relationship with traditional
therapies are emerging issues worldwide. This section includes citations on general
use of complementary therapies with several references specifically on dietary
supplements.
Palliation
Palliation is care given to patients and families who face life-threatening illness
by providing pain and symptom relief, spiritual and psychosocial support from diagnosis
to the end of life and bereavement (WHO 2006). This review suggests a general
misperception about palliation as being only hospice care for the end-stage of life.
Emerging issues in palliation include the use of behavioral interventions (Redd et al.
2001) and mind-body therapies (Astin et al. 2003) in symptom management versus an
Emerging Issues 11
emphasis on medications. The research work on the role of chemotherapy and
radiation in palliation is also reviewed in this document.
Emerging Issues 12
PART I: LITERATURE REVIEW WITHOUT ABSTRACTS
Emerging Issues 13
SECTION A: PRIMARY PREVENTION
Emerging Issues 14
Behavior
Balluz, L., I. Ahluwalia, et al. (2004). "Surveillance for certain health behaviors among
selected local areas--United States, Behavioral Risk Factor Surveillance System, 2002."
MMWR Surveill Summ 53(5): 1-100.
Tobacco Use
Boffetta, P. (2004). "Epidemiology of environmental and occupational cancer."
Oncogene 23(38): 6392-403.
Centers for Disease Control and Prevention, CDC (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
Centers for Disease Control and Prevention, CDC (2003). Promising Practices in
Chronic Disease Prevention and Control: A Public Health Framework for Action, United
States Department of Health and Human Services: 195.
Centers for Disease Control and Prevention, CDC (2003). Second National Report on
Human Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services National Center for Environmental Health Division of Laboratory Sciences:
257.
Centers for Disease Control and Prevention, CDC (2005). Third National Report on
Human Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services Centers for Disease Control and Prevention National Center for Environmental
Health Division of Laboratory Sciences: 475.
Chapman, S. and J. Liberman (2005). "Ensuring smokers are adequately informed:
reflections on consumer rights, manufacturer responsibilities, and policy implications."
Tob Control 14 Suppl 2: ii8-13.
Clapp, Richard W., Genevieve K. Howe and Molly M. Jacobs (2005). Environmental and
Occupational Causes of Cancer: A Review of Recent Scientific Literature, University of
Massachusetts Lowell: 50.
Dacey, Lawrence J. and David W. Johnstone (2005). "Reducing the Risk of Lung
Cancer." JAMA: Journal of the American Medical Association 294(12): 1550-1551.
Donovan, R. J., J. Jancey and S. Jones (2002). "Tobacco point of sale advertising
increases positive brand user imagery." Tob Control 11(3): 191-4.
Emerging Issues 15
Hackbarth, D. P., D. Schnopp-Wyatt, D. Katz, J. Williams, B. Silvestri and M. Pfleger
(2001). "Collaborative research and action to control the geographic placement of
outdoor advertising of alcohol and tobacco products in Chicago." Public Health Rep
116(6): 558-67.
Henriksen, L. and S. P. Fortmann (2002). "Young adults' opinions of Philip Morris and
its television advertising." Tob Control 11(3): 236-40.
Kelsey, K. T., T. Hirao, S. Hirao, T. Devi-Ashok, H. H. Nelson, A. Andrew, J. Colt, D.
Baris, J. S. Morris, A. Schned and M. Karagas (2005). "TP53 alterations and patterns of
carcinogen exposure in a U.S. population-based study of bladder cancer." Int J Cancer
117(3): 370-5.
Kilfoy, B. A., K. S. Hudmon and J. R. Mande (2007). "Tobacco control in state
comprehensive cancer control plans: opportunities for decreasing tobacco-related
disease." Prev Chronic Dis 4(3): A61.
Kuper, H., L. Titus-Ernstoff, B. L. Harlow and D. W. Cramer (2000). "Population based
study of coffee, alcohol and tobacco use and risk of ovarian cancer." Int J Cancer 88(2):
313-8.
Marsit, C. J., M. R. Karagas, H. Danaee, M. Liu, A. Andrew, A. Schned, H. H. Nelson
and K. T. Kelsey (2006). "Carcinogen exposure and gene promoter hypermethylation in
bladder cancer." Carcinogenesis 27(1): 112-6.
Moritsugu, K. P. (2007). "The 2006 Report of the Surgeon General: the health
consequences of involuntary exposure to tobacco smoke." Am J Prev Med 32(6): 542-3.
National Cancer Institute (2004). Cancer and the Environment: What You Need to
Know, What You Can Do, U.S. Department of Health and Human Services: 47.
Silva, Idos S (2002). "Alcohol, tobacco and breast cancer: should alcohol be
condemned and tobacco acquitted?" British Journal of Cancer 87(12): 12.
Strahan, E. J., K. White, G. T. Fong, L. R. Fabrigar, M. P. Zanna and R. Cameron
(2002). "Enhancing the effectiveness of tobacco package warning labels: a social
psychological perspective." Tob Control 11(3): 183-90.
U.S. Department of Health and Human Services, U.S.DHHS (2006). The Health
Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon
General. U.S. Department of Health and Human Services, Centers for Disease Control
and Prevention, Coordinating Center for Health Promotion, National Center for Chronic
Disease Prevention and Health Promotion, Office on Smoking and Health, U.S.
Department of Health and Human Services, Centers for Disease COntrol and
Prevention: 721.
Emerging Issues 16
Westmaas, J. L. and T. H. Brandon (2004). "Reducing risk in smokers." Curr Opin Pulm
Med 10(4): 284-8.
Williams, A., E. Peterson, S. Knight, M. Hiller and A. Pelletier (2004). "Survey of
restaurants regarding smoking policies." J Public Health Manag Pract 10(1): 35-40.
Zakarian, J. M., M. F. Hovell, R. D. Sandweiss, C. R. Hofstetter, G. E. Matt, J. T.
Bernert, J. Pirkle and S. K. Hammond (2004). "Behavioral counseling for reducing
children's ETS exposure: implementation in community clinics." Nicotine Tob Res 6(6):
1061-74.
Zanieri, L., P. Galvan, L. Checchini, A. Cincinelli, L. Lepri, G. P. Donzelli and M. Del
Bubba (2007). "Polycyclic aromatic hydrocarbons (PAHs) in human milk from Italian
women: influence of cigarette smoking and residential area." Chemosphere 67(7): 126574.
Emerging Issues 17
Exposure to Radiation
Ionizing Radiation
Albrecht M, Müller K, Köhn FM, Meineke V, Mayerhofer A. (2007). "Ionizing radiation
induces degranulation of human mast cells and release of tryptase." International
journal of radiation biology 83(8): 535-41.
Belson, Martin, Beverely Kingsley and Adrianne Holmes (2007/1). "Risk Factors for
Acute Leukemia in Children: A Review." Environmental Health Perspectives 115(1):
138-145.
Cardis, Elisabeth, Janet Hall and Sean V Tavtigian (2007). "Identification of women with
an increased risk of developing radiation-induced breast cancer." Breast Cancer
Research 9(106).
Chicago Tribune. (2007). "Overexposure to radiation is on the rise." from
http://www.chicagotribune.com/entertainment/chi0626_health_radiation_rjun26,1,3230065.story?track=rss.
Geggel, Laura. (2007). "Radiation from health scans causes concern: Increasing use
stirs cancer fears." from
http://seattlepi.nwsource.com/local/322432_radiation05.html?source=rss.
Lichter, Michael D., Margaret R. Karagas, Leila A. Mott, Steven K. Spencer, Therese A.
Stukel, E. Robert Greenberg and Group for the New Hampshire Skin Cancer Study
(2000). "Therapeutic Ionizing Radiation and the Incidence of Basal Cell Carcinoma and
Squamous Cell Carcinoma." Arch Dermatol 136(8): 1007-1011.
Medical News Today. (2007). "Health Physics Society Annual Meeting To Address
Radiation Safety Issues - Including Improving Detection Of Breast Cancer." from
http://www.medicalnewstoday.com/medicalnews.php?newsid=75886.
World Health Organization. (2007). "What is Ionizing Radiation?" from
http://www.who.int/ionizing_radiation/about/what_is_ir/en/index.html.
Ultraviolet Radiation
Karagas, M. R., E. R. Greenberg, S. K. Spencer, T. A. Stukel and L. A. Mott (1999).
"Increase in incidence rates of basal cell and squamous cell skin cancer in New
Hampshire, USA. New Hampshire Skin Cancer Study Group." Int J Cancer 81(4): 5559.
Emerging Issues 18
Karagas, Margaret R., Virginia A. Stannard, Leila A. Mott, Mary Jo Slattery, Steven K.
Spencer and Martin A. Weinstock (2002). "Use of Tanning Devices and Risk of Basal
Cell and Squamous Cell Skin Cancers." J. Natl. Cancer Inst. 94(3): 224-226.
Karagas, M. R., M. S. Zens, H. H. Nelson, K. Mabuchi, A. E. Perry, T. A. Stukel, L. A.
Mott, A. S. Andrew, K. M. Applebaum and M. Linet (2007). "Measures of cumulative
exposure from a standardized sun exposure history questionnaire: a comparison with
histologic assessment of solar skin damage." Am J Epidemiol 165(6): 719-26.
Kricker, Anne and Bruce Armstrong (2006). "Does sunlight have a beneficial influence
on certain cancers?" Progress in Biophysics & Molecular Biology 92(1): 132-139.
Lichter, Michael D., Margaret R. Karagas, Leila A. Mott, Steven K. Spencer, Therese A.
Stukel, E. Robert Greenberg and Group for the New Hampshire Skin Cancer Study
(2000). "Therapeutic Ionizing Radiation and the Incidence of Basal Cell Carcinoma and
Squamous Cell Carcinoma." Arch Dermatol 136(8): 1007-1011.
Miller, K. L., M. R. Karagas, P. Kraft, D. J. Hunter, P. J. Catalano, S. H. Byler and H. H.
Nelson (2006). "XPA, haplotypes, and risk of basal and squamous cell carcinoma."
Carcinogenesis 27(8): 1670-5.
Nelson, H. H., B. Christensen and M. R. Karagas (2005). "The XPC poly-AT
polymorphism in non-melanoma skin cancer." Cancer Lett 222(2): 205-9.
Nelson, H. H., K. T. Kelsey, L. A. Mott and M. R. Karagas (2002). "The XRCC1
Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of geneenvironment interaction." Cancer Res 62(1): 152-5.
Olson, A. L., C. Gaffney, P. Starr, J. J. Gibson, B. F. Cole and A. J. Dietrich (2007).
"SunSafe in the Middle School Years: a community-wide intervention to change earlyadolescent sun protection." Pediatrics 119(1): e247-56.
Press Release. (2007). "Survey reveals lack of awareness that US sunscreens provide
insufficient protection against skin cancer
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Stryker, J. E., A. L. Yaroch, R. P. Moser, A. Atienza and K. Glanz (2007). "Prevalence of
sunless tanning product use and related behaviors among adults in the United States:
results from a national survey." J Am Acad Dermatol 56(3): 387-90.
Emerging Issues 19
Environmental Pollutants
General Exposure to Pollution
Angerer, J., U. Ewers, et al. (2007/5). "Human biomonitoring: State of the art."
International Journal of Hygiene & Environmental Health 210(3/4): 201-228.
Aschengrau, A. (2006/6). "Drinking water detective story: connecting water
contamination and disease." Massachusetts Nurse 77(5): 9-9.
Boffetta, P. (2004). "Epidemiology of environmental and occupational cancer."
Oncogene 23(38): 6392-403.
Boffetta, P. (2006/9). "Human cancer from environmental pollutants: The
epidemiological evidence." Mutation Research/Genetic Toxicology & Environmental
Mutagenesis 608(2): 157-162.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Buffler, P. A., M. L. Kwan, et al. (2005). "Environmental and Genetic Risk Factors for
Childhood Leukemia: Appraising the Evidence." Cancer Investigation 23(1): 60-75.
Centers for Disease Control and Prevention, C. (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
Centers for Disease Control and Prevention (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
Centers for Disease Control and Prevention (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
Centers for Disease Control and Prevention. (2003). Second National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human Services
National Center for Environmental Health Division of Laboratory Sciences: 257.
Centers for Disease Control and Prevention. (2005). Third National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human Services
Centers for Disease Control and Prevention National Center for Environmental Health
Division of Laboratory Sciences: 475.
Emerging Issues 20
Clapp, R. W., G. K. Howe, et al. (2005). Environmental and Occupational Causes of
Cancer: A Review of Recent Scientific Literature, University of Massachusetts Lowell:
50.
Greenberg, M. R. (2007). Contemporary Environmental and Occupational Health
Issues: More Breadth and Depth. American Journal of Public Health: 395-397.
Koehler, D. A., D. H. Bennett, et al. (2005). "Rethinking Environmental Performance
from a Public Health Perspective: A Comparative Industry Analysis." Journal of
Industrial Ecology 9(3): 143-167.
McNally, R. J. Q. and L. Parker (2006/4). "Environmental factors and childhood acute
leukemias and lymphomas." Leukemia & Lymphoma 47(4): 583-598.
National Cancer Institute (2004). Cancer and the Environment: What You Need to
Know, What You Can Do, U.S. Department of Health and Human Services: 47.
Neri, M., S. Bonassi, et al. (2006/1). "Children's exposure to environmental pollutants
and biomarkers of genetic damage: I. Overview and critical issues." Mutation
Research/Reviews in Mutation Research 612(1): 1-13.
Richardson, S. D. and T. A. Ternes (2005). "Water Analysis: Emerging Contaminants
and Current Issues." Anal. Chem. 77(12): 3807-3838.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Role of the Environment. Nancy Ryan. Lee, NH, New Hampshire Breast
Cancer Coalition.
Tsai, J., W. E. Kaye, et al. (2006/1). "Wilms tumor and exposures to residential and
occupational hazardous chemicals." International Journal of Hygiene & Environmental
Health 209(1): 57-64.
Van Den Hazel, P., M. Zuurbier, et al. (2006). "Today's epidemics in children: Possible
relations to environmental pollution and suggested preventive measures." Acta
Paediatrica 95: 18-25.
Wigle, D. T., T. E. Arbuckle, et al. (2007/1). "Environmental Hazards: Evidence for
Effects on Child Health." Journal of Toxicology & Environmental Health: Part B 10(1): 339.
Arsenic
Andrew, A. S., J. L. Burgess, M. M. Meza, E. Demidenko, M. G. Waugh, J. W. Hamilton
and M. R. Karagas (2006). "Arsenic exposure is associated with decreased DNA repair
in vitro and in individuals exposed to drinking water arsenic." Environ Health Perspect
114(8): 1193-8.
Emerging Issues 21
Andrew, A. S., M. R. Karagas and J. W. Hamilton (2003). "Decreased DNA repair gene
expression among individuals exposed to arsenic in United States drinking water." Int J
Cancer 104(3): 263-8.
Ayotte, J. D., D. Baris, K. P. Cantor, J. Colt, G. R. Robinson, Jr., J. H. Lubin, M.
Karagas, R. N. Hoover, J. F. Fraumeni, Jr. and D. T. Silverman (2006). "Bladder cancer
mortality and private well use in New England: an ecological study." J Epidemiol
Community Health 60(2): 168-72.
Ayotte, J. D., B. T. Nolan, J. R. Nuckols, K. P. Cantor, G. R. Robinson, Jr., D. Baris, L.
Hayes, M. Karagas, W. Bress, D. T. Silverman and J. H. Lubin (2006). "Modeling the
probability of arsenic in groundwater in New England as a tool for exposure
assessment." Environ Sci Technol 40(11): 3578-85.
Bissen, Monique and Fritz H. Frimmel (2003). "Arsenic - a Review. Part I: Occurrence,
Toxicity, Speciation, Mobility." Acta hydrochimica et hydrobiologica 31(1): 9-18.
Bodwell, J. E., L. A. Kingsley and J. W. Hamilton (2004). "Arsenic at very low
concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GRmediated gene repression: complex dose-response effects are closely correlated with
levels of activated GR and require a functional GR DNA binding domain." Chem Res
Toxicol 17(8): 1064-76.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Colt, J. S., D. Baris, S. F. Clark, J. D. Ayotte, M. Ward, J. R. Nuckols, K. P. Cantor, D. T.
Silverman and M. Karagas (2002). "Sampling private wells at past homes to estimate
arsenic exposure: a methodologic study in New England." J Expo Anal Environ
Epidemiol 12(5): 329-34.
Healthy New Hampshire. (2007). "Environmental Health: Arsenic." Retrieved June 2,
2007, from http://www.healthynh2010.org/arsenic.htm.
Karagas, M. R., C. X. Le, S. Morris, J. Blum, X. Lu, V. Spate, M. Carey, V. Stannard, B.
Klaue and T. D. Tosteson (2001). "Markers of low level arsenic exposure for evaluating
human cancer risks in a US population." Int J Occup Med Environ Health 14(2): 171-5.
Karagas, M. R., J. S. Morris, J. E. Weiss, V. Spate, C. Baskett and E. R. Greenberg
(1996). "Toenail samples as an indicator of drinking water arsenic exposure." Cancer
Epidemiol Biomarkers Prev 5(10): 849-52.
Karagas, M. R., S. Park, H. H. Nelson, A. S. Andrew, L. Mott, A. Schned and K. T.
Kelsey (2005). "Methylenetetrahydrofolate reductase (MTHFR) variants and bladder
cancer: a population-based case-control study." Int J Hyg Environ Health 208(5): 321-7.
Emerging Issues 22
Karagas, M. R., T. A. Stukel, J. S. Morris, T. D. Tosteson, J. E. Weiss, S. K. Spencer
and E. R. Greenberg (2001). "Skin cancer risk in relation to toenail arsenic
concentrations in a US population-based case-control study." Am J Epidemiol 153(6):
559-65.
Karagas, M. R., T. A. Stukel and T. D. Tosteson (2002). "Assessment of cancer risk and
environmental levels of arsenic in New Hampshire." Int J Hyg Environ Health 205(1-2):
85-94.
Karagas, M. R., T. D. Tosteson, J. Blum, B. Klaue, J. E. Weiss, V. Stannard, V. Spate
and J. S. Morris (2000). "Measurement of low levels of arsenic exposure: a comparison
of water and toenail concentrations." Am J Epidemiol 152(1): 84-90.
Karagas, M. R., T. D. Tosteson, J. Blum, J. S. Morris, J. A. Baron and B. Klaue (1998).
"Design of an epidemiologic study of drinking water arsenic exposure and skin and
bladder cancer risk in a U.S. population." Environ Health Perspect 106 Suppl 4: 104750.
Karagas, M. R., T. D. Tosteson, J. S. Morris, E. Demidenko, L. A. Mott, J. Heaney and
A. Schned (2004). "Incidence of transitional cell carcinoma of the bladder and arsenic
exposure in New Hampshire." Cancer Causes Control 15(5): 465-72.
Kelsey, K. T., T. Hirao, S. Hirao, T. Devi-Ashok, H. H. Nelson, A. Andrew, J. Colt, D.
Baris, J. S. Morris, A. Schned and M. Karagas (2005). "TP53 alterations and patterns of
carcinogen exposure in a U.S. population-based study of bladder cancer." Int J Cancer
117(3): 370-5.
Marsit, C. J., M. R. Karagas, H. Danaee, M. Liu, A. Andrew, A. Schned, H. H. Nelson
and K. T. Kelsey (2006). "Carcinogen exposure and gene promoter hypermethylation in
bladder cancer." Carcinogenesis 27(1): 112-6.
New Hampshire Department of Environmental Services. (2006). "Arsenic in Drinking
Water." Retrieved May 27, 2007, from http://www.des.state.nh.us/factsheets/ws/ws-32.htm.
New Hampshire Department of Environmental Services. (2007). "Arsenic:
Comprehensive Health Information Summary." Retrieved May 27, 2007, from
http://www.des.state.nh.us/factsheets/ehp/ard-ehp-1a.htm.
New Hampshire Department of Environmental Services. (2007). "Arsenic: Health
Information Summary." Retrieved May 27, 2007, 2007, from
http://www.des.state.nh.us/factsheets/ehp/ard-ehp-1.htm.
Wickre, J. B., C. L. Folt, S. Sturup and M. R. Karagas (2004). "Environmental exposure
and fingernail analysis of arsenic and mercury in children and adults in a Nicaraguan
gold mining community." Arch Environ Health 59(8): 400-9.
Emerging Issues 23
MtBE
Belpoggi, F., M. Soffritti, et al. (1997). "Results of long-term experimental studies on the
carcinogenicity of methyl tert-butyl ether." Ann N Y Acad Sci 837: 77-95.
Belpoggi, F., M. Soffritti, et al. (1995). "Methyl-tertiary-butyl ether (MTBE)--a gasoline
additive--causes testicular and lymphohaematopoietic cancers in rats." Toxicol Ind
Health 11(2): 119-49.
Borghoff, S. J., J. E. Murphy, et al. (1996). "Development of physiologically based
pharmacokinetic model for methyl tertiary-butyl ether and tertiary-butanol in male
Fisher-344 rats." Fundam Appl Toxicol 30(2): 264-75.
Casanova, M. and H. A. Heck (1997). "Lack of evidence for the involvement of
formaldehyde in the hepatocarcinogenicity of methyl tertiary-butyl ether in CD-1 mice."
Chem Biol Interact 105(2): 131-43.
Cruzan, G., S. J. Borghoff, et al. (2007). "Methyl tertiary-butyl ether mode of action for
cancer endpoints in rodents." Regul Toxicol Pharmacol 47(2): 156-65.
de Peyster, A., K. J. MacLean, et al. (2003). "Subchronic studies in Sprague-Dawley
rats to investigate mechanisms of MTBE-induced Leydig cell cancer." Toxicol Sci 72(1):
31-42.
Iavicoli, I., G. Carelli, et al. (2002). "Methyl-tertiary-butyl ether (MTBE) inhibits growth
and induces cell transformation in rodent fibroblasts." Anticancer Res 22(4): 2173-7.
Mehlman, M. A. (1990). "Dangerous properties of petroleum-refining products:
carcinogenicity of motor fuels (gasoline)." Teratog Carcinog Mutagen 10(5): 399-408.
Mehlman, M. A. (1996). "Dangerous and cancer-causing properties of products and
chemicals in the oil-refining and petrochemical industry--Part XXII: Health hazards from
exposure to gasoline containing methyl tertiary butyl ether: study of New Jersey
residents." Toxicol Ind Health 12(5): 613-27.
Mehlman, M. A. (1998). "Hazardous pollutant: gasoline containing methyl tertiary-butyl
ether (MTBE)." Int J Occup Environ Health 4(2): 134-5.
Mehlman, M. A. (1999). "Cancer risk from exposure to motor fuel containing MTBE:
"reasonably anticipated to be a human carcinogen"." Int J Occup Environ Health 5(4):
323-4.
Mehlman, M. A. (2002). "Carcinogenicity of methyl-tertiary butyl ether in gasoline." Ann
N Y Acad Sci 982: 149-59.
Emerging Issues 24
Mennear, J. H. (1997). "Carcinogenicity studies on MTBE: critical review and
interpretation." Risk Anal 17(6): 673-81.
Moser, G. J., B. A. Wong, et al. (1996). "Methyl tertiary butyl ether lacks tumorpromoting activity in N-nitrosodiethylamine-initiated B6C3F1 female mouse liver."
Carcinogenesis 17(12): 2753-61.
Snelling, J., M. O. Barnett, et al. (2006). "Methyl tertiary hexyl ether and methyl tertiary
octyl ether as gasoline oxygenates: assessing risks from atmospheric dispersion and
deposition." J Air Waste Manag Assoc 56(10): 1484-92.
Spitzer, H. L. (1997). "An analysis of the health benefits associated with the use of
MTBE reformulated gasoline and oxygenated fuels in reducing atmospheric
concentrations of selected volatile organic compounds." Risk Anal 17(6): 683-91.
Pesticides
"NEW STUDIES CHALLENGE PESTICIDE SAFETY." (2006). Ecologist 36(2): 9-9.
"Quebec bans 2,4-D." (2006/6/1). Environmental Science & Technology 40(11): 34473447.
Turf Pesticides and Cancer Risk Database (2007). Cornell University College of
Veterinary Medicine Program on Breast Cancer and Environmental Risk Factors.
Adler, Tina (2003/11). "Methyl Bromide Ups Prostate Risk." Environmental Health
Perspectives 111(14): A754-A754.
Alavanja, Michael and Matthew Bonner (2005). "Pesticides and Human Cancers."
Cancer Investigation 23(8): 700-711.
Barrett, Julia R. (2006/9). "Pyrethroids in the Home." Environmental Health
Perspectives 114(9): A544-A544.
Belson, Martin, Beverely Kingsley and Adrianne Holmes (2007/1). "Risk Factors for
Acute Leukemia in Children: A Review." Environmental Health Perspectives 115(1):
138-145.
Boffetta, Paolo (2006/9). "Human cancer from environmental pollutants: The
epidemiological evidence." Mutation Research/Genetic Toxicology & Environmental
Mutagenesis 608(2): 157-162.
Brechka, Nicole (2006/9). all about organics. Better Nutrition, Active Interest Media, Inc.
68: 6-6.
Emerging Issues 25
Buffler, Patricia A., Marilyn L. Kwan, Peggy Reynolds and Kevin Y. Urayama (2005).
"Environmental and Genetic Risk Factors for Childhood Leukemia: Appraising the
Evidence." Cancer Investigation 23(1): 60-75.
Chen, Zhi, Leslie Robison, Roger Giller, Mark Krailo, Mary Davis, Stella Davies and
Xiao Ou Shu (2006/1). "Environmental exposure to residential pesticides, chemicals,
dusts, fumes, and metals, and risk of childhood germ cell tumors." International Journal
of Hygiene & Environmental Health 209(1): 31-40.
Colt, Joanne S., Mancer J. Cyr, Shelia H. Zahm, Geoffrey S. Tobias and Patricia Hartge
(2007/2). "Inferring Past Pesticide Exposures: A Matrix of Individual Active Ingredients
in Home and Garden Pesticides Used in Past Decades." Environmental Health
Perspectives 115(2): 248-254.
Cooney, Maureen A., Julie L. Daniels, Julie A. Ross, Norman E. Breslow, Brad H.
Pollock and Andrew F. Olshan (2007/1). "Household Pesticides and the Risk of Wilms
Tumor." Environmental Health Perspectives 115(1): 134-137.
Fortes, Cristina, Simona Mastroeni, Franco Melchi, Maria Antonietta Pilla, Massimo
Alotto, Gianluca Antonelli, Diana Camaione, Simone Bolli, Elisabetta Luchetti and Paolo
Pasquini (2007/4). "The association between residential pesticide use and cutaneous
melanoma." European Journal of Cancer 43(6): 1066-1075.
Hughes, Glenys (2006/8). "PESTICIDES AND RISK OF LEUKAEMIA IN CHILDREN."
Journal of Epidemiology & Community Health 60(8): 736-736.
Infante-Rivard, Claire and Scott Weichenthal (2007/1). "Pesticides and Childhood
Cancer: An Update of Zahm and Ward's 1998 Review." Journal of Toxicology &
Environmental Health: Part B 10(1): 81-99.
Jurewicz, Joanna and Wojciech Hanke (2006/7). "EXPOSURE TO PESTICIDES AND
CHILDHOOD CANCER RISK: HAS THERE BEEN ANY PROGRESS IN
EPIDEMIOLOGICAL STUDIES?" International Journal of Occupational Medicine &
Environmental Health 19(3): 152-169.
Jurewicz, Joanna, Wojciech Hanke, Carolina Johansson, Christofer Lundqvist, Sandra
Ceccatelli, Peter Van Den Hazel, Margaret Saunders and Rolf Zetterstr+¦m (2006/10).
"Adverse health effects of children's exposure to pesticides: What do we really know
and what can be done about it." Acta Paediatrica 95: 71-80.
Khanjani, Narges, Jan Lucas Hoving, Andrew Benjamin Forbes and Malcolm Ross Sim
(2007/5). "Systematic Review and Meta-analysis of Cyclodiene Insecticides and Breast
Cancer." Journal of Environmental Science & Health, Part C -- Environmental
Carcinogenesis & Ecotoxicology Reviews 25(1): 23-52.
Emerging Issues 26
Marusek, Jennifer C., Myles G. Cockburn, Paul K. Mills and Beate R. Ritz (2006/2).
"Control Selection and Pesticide Exposure Assessment Via GIS in Prostate Cancer
Studies." American Journal of Preventive Medicine 30: S109-S116.
Nasterlack, Michael (2006/9). "Do pesticides cause childhood cancer?" International
Archives of Occupational & Environmental Health 79(7): 536-544.
Nielsen, Susan Searles, Beth A. Mueller, Anneclaire J. De Roos, Hannah Malia Viernes,
Federico M. Farin and Harvey Checkoway (2005/7). "Risk of Brain Tumors in Children
and Susceptibility to Organophosphorus Insecticides: The Potential Role of
Paraoxonase (PON1)." Environmental Health Perspectives 113(7): 909-913.
Rekha, S.N. Naik and R. Prasad (2006/11). "Pesticide residue in organic and
conventional food-risk analysis." Journal of Chemical Health & Safety 13(6): 12-19.
Teitelbaum, Susan L., Marilie D. Gammon, Julie A. Britton, Alfred I. Neugut, Bruce Levin
and Steven D. Stellman (2007/3). "Reported Residential Pesticide Use and Breast
Cancer Risk on Long Island, New York." American Journal of Epidemiology 165(6): 643651.
Tsai, James, Wendy E. Kaye and Frank J. Bove (2006/1). "Wilms tumor and exposures
to residential and occupational hazardous chemicals." International Journal of Hygiene
& Environmental Health 209(1): 57-64.
Wigle, Donald T., Tye E. Arbuckle, Mark Walker, Michael G. Wade, Liu Shiliang and
Daniel Krewski (2007/1). "Environmental Hazards: Evidence for Effects on Child
Health." Journal of Toxicology & Environmental Health: Part B 10(1): 3-39.
Radon
Auvinen, A., L. Salonen, et al. (2005). "Radon and other natural radionuclides in
drinking water and risk of stomach cancer: a case-cohort study in Finland." Int J Cancer
114(1): 109-13.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Boudette, E. L. (1994). "Radon in New Hampshire." GEO-2 Retrieved June 2, 2007,
2007, from http://www.des.state.nh.us/factsheets/geo/geo-2.htm.
Healthy New Hampshire. (2007). "Environmental Health: Radon." Retrieved June 2,
2007, from http://www.healthynh2010.org/radon.htm.
Kendall, G. M. and T. J. Smith (2005). "Doses from radon and its decay products to
children." J Radiol Prot 25(3): 241-56.
Emerging Issues 27
Kennedy, C. A., A. M. Gray, et al. (2002). "The cost-effectiveness of residential radon
remediation programmes: assumptions about benefits stream profiles over time." J
Environ Radioact 59(1): 19-28.
Krewski, D., J. H. Lubin, J. M. Zielinski, M. Alavanja, V. S. Catalan, R. W. Field, J. B.
Klotz, E. G. Letourneau, C. F. Lynch, J. L. Lyon, D. P. Sandler, J. B. Schoenberg, D. J.
Steck, J. A. Stolwijk, C. Weinberg and H. B. Wilcox (2006). "A combined analysis of
North American case-control studies of residential radon and lung cancer." J Toxicol
Environ Health A 69(7): 533-97.
Kurttio, P., L. Salonen, et al. (2006). "Well water radioactivity and risk of cancers of the
urinary organs." Environ Res 102(3): 333-8.
New Hampshire Department of Environmental Services. (2005). "Radon in Air and
Water: An Overview For The Homeowner " WD-WSEB-3-12 Retrieved June 2, 2007,
2007, from http://des.state.nh.us/factsheets/ws/ws-3-12.htm.
Riesenfeld, E. P., T. W. Marcy, et al. (2007). "Radon awareness and mitigation in
Vermont: a public health survey." Health Phys 92(5): 425-31.
Samet, J. M. (2006). "Residential radon and lung cancer: end of the story?" J Toxicol
Environ Health A 69(7): 527-31.
Steck, D. J. and R. W. Field (2006). "Dosimetric challenges for residential radon
epidemiology." J Toxicol Environ Health A 69(7): 655-64.
Takahashi, M. and S. Kojima (2006). "Suppression of atopic dermatitis and tumor
metastasis in mice by small amounts of radon." Radiat Res 165(3): 337-42.
Wood, W. W., T. F. Kraemer, et al. (2004). "Radon (222Rn) in ground water of fractured
rocks: a diffusion/ion exchange model." Ground Water 42(4): 552-67.
Zielinski, J. M., Z. Carr, D. Krewski and M. Repacholi (2006). "World Health
Organization's International Radon Project." J Toxicol Environ Health A 69(7): 759-69.
Other Pollutants
Gaylor, DW, SJ Culp, LS Goldstein and FA Beland (2000). "Cancer risk estimation for
mixtures of coal tars and benzo(a)pyrene." Risk Analysis 20(1): 81-85.
Harper, J. W. (2007/03/29). "Chemical biology: A degrading solution to pollution."
Nature 446(7135): 499-500.
Emerging Issues 28
Melber, Christine, Janet Kielhorn and Inge Mangelsdorf. (2004). "Concise International
Chemical Assessment Document 62: COAL TAR CREOSOTE." Retrieved July 1,
2007, from http://www.inchem.org/documents/cicads/cicads/cicad62.htm#1.0.
New Hampshire Department of Health and Human Services Bureau of Health Risk
Assessment and Agency for Toxic Substances and Disease Registry. (2000, June 12,
2007). "PUBLIC HEALTH ASSESSMENT: MESSER STREET MANUFACTURED GAS
PLANT, LACONIA, BELKNAP COUNTY, NEW HAMPSHIRE
", from http://www.atsdr.cdc.gov/hac/PHA/messer/msm_toc.html.
Emerging Issues 29
Diet and Nutrition
General
Baggiani, C., L. Anfossi, et al. (2007/5). "Solid phase extraction of food contaminants
using molecular imprinted polymers." Analytica Chimica Acta 591(1): 29-39.
Brechka, N. (2006/9). all about organics. Better Nutrition, Active Interest Media, Inc. 68:
6-6.
BBC News. (2007). "Sausage additive linked to cancer." from
http://news.bbc.co.uk/2/hi/health/6286834.stm.
Chicago Tribune. (2007, July 10, 2007). "Meat-sweet diet linked to breast cancer." from
http://featuresblogs.chicagotribune.com/features_julieshealthclub/2007/07/meat-sweetdiet.html.
Dai, J., J. D. Patel and R. J. Mumper (2007). "Characterization of blackberry extract and
its antiproliferative and anti-inflammatory properties." J Med Food 10(2): 258-65.
Gonzalez, Carlos A. and Jordi Salas-Salvado (2006). "The potential of nuts in the
prevention of cancer." British Journal of Nutrition 96(1, Suppl. 2): S87-S94.
Hu, Frank B. (2003). "The Mediterranean Diet and Mortality- Olive Oil and Beyond." N
ENGL J MED 348(26): 2595-2596.
Keck, Anna-Sigrid, Qingyan Qiao and Elizabeth H. Jeffery (2003). "Food Matrix Effects
on Bioactivity of Broccoli-Derived Sulforaphane in Liver and Colon of F344 Rats " J.
Agric. Food Chem. 51(11): 3320-3327.
Knoops, Kim T. B., Lisette C. P. G. M. de Groot, Daan Kromhout, Anne-Elisabeth
Perrin, Olga Moreiras-Varela, Alessandro Menotti and Wija A. van Staveren (2004).
"Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly Men and
Women: The HALE Project." JAMA 292(12): 1433-1439.
Meyer, Catherine (2004). "Scientists Probe Role of Vitamin D: Deficiency a Significant
Problem, Experts Say." JAMA 292(12): 1416-1418.
Schwartz, GG and HG. Skinner (2007). "Vitamin D status and cancer: new insights." 10
1(6-11).
Shigemura, K., J. L. Arbiser, S. Y. Sun, M. Zayzafoon, P. A. Johnstone, M. Fujisawa, A.
Gotoh, B. Weksler, H. E. Zhau and L. W. Chung (2007). "Honokiol, a natural plant
Emerging Issues 30
product, inhibits the bone metastatic growth of human prostate cancer cells." Cancer
109(7): 1279-89.
Vastag, Brian (2004). "FDA Reviews Expanded Claims on Health Benefits of Certain
Foods." Journal of the National Cancer Institute 96(16): 1198-1199.
Breast Cancer, Diet, & Nutrition
Chagpar, A. B., K. M. McMasters, et al. (2007). "Body Mass Index Influences Palpability
But Not Stage of Breast Cancer at Diagnosis." American Surgeon 73(6): 555-560.
Pierce, J. P., L. Natarajan, et al. (2007). "Influence of a Diet Very High in Vegetables,
Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer:
The Women's Healthy Eating and Living (WHEL) Randomized Trial." Journal of the
American Medical Association (JAMA) 298(3): 289-298.
Pierce, J. P., M. L. Stefanick, et al. (2007). "Greater Survival After Breast Cancer in
Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity."
Journal of Clinical Oncology 25(17): 2345-2351.
Colon Cancer, Diet, & Nutrition
Dupertuis YM, Meguid MM, Pichard C. (2007). "Colon cancer therapy: new perspectives
of nutritional manipulations using polyunsaturated fatty acids." Current opinions in
nutritional metabolic care 10(4): 427-32.
Giovannucci E, Michaud D. (2007). "The role of obesity and related metabolic
disturbances in cancers of the colon, prostate, and pancreas." Gastroenterology 132(6):
2208-25.
Grant, William B. (2006). "Epidemiology of disease risks in relation to vitamin D
insufficiency." Progress in Biophysics & Molecular Biology 92(1): 65-79.
Gutt CN, Brinkmann L, Mehrabi A, Fonouni H, Müller-Stich BP, Vetter G, Stein JM,
Schemmer P, Büchler MW. (2007). "Dietary omega-3-polyunsaturated fatty acids
prevent the development of metastases of colon carcinoma in rat liver." European
journal of cancer ahead of print.
positive, only 21.4% of the target animals showed tumor after omega-3-fatty acid (P <
Hu J, Morrison H, Mery L, Desmeules M, Macleod M. (2007). "Diet and vitamin or
mineral supplementation and risk of colon cancer by subsite in Canada." European
journal of cancer prevention 16(4): 275-91.
Kimura Y, Kono S, Toyomura K, Nagano J, Mizoue T, Moore MA, Mibu R, Tanaka M,
Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T,
Emerging Issues 31
Takenaka K, Ichimiya H, Imaizumi N. (2007). "Meat, fish and fat intake in relation to
subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study."
Cancer Science 98(4): 590-7.
Lee BB, Cha MR, Kim SY, Park E, Park HR, Lee SC. (2007). "Antioxidative and
Anticancer Activity of Extracts of Cherry (Prunus serrulata var. spontanea) Blossoms."
PLant foods and human nutrition ahead of print.
Mannisto, Satu, Shiaw-Shyuan Yaun, David J. Hunter, Donna Spiegelman, Hans-Olov
Adami, Demetrius Albanes, Piet A. van den Brandt, Julie E. Buring, James R. Cerhan,
Graham A. Colditz, Jo L. Freudenheim, Charles S. Fuchs, Edward Giovannucci, R.
Alexandra Goldbohm, Lisa Harnack, Michael Leitzmann, Marjorie L. McCullough,
Anthony B. Miller, Thomas E. Rohan, Arthur Schatzkin, Jarmo Virtamo, Walter C.
Willett, Alicja Wolk, Shumin M. Zhang and Stephanie A. Smith-Warner (2007). "Dietary
carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies."
American Journal of Epidemiology 165(3): 246-255.
Nilsson U, Johansson M, Nilsson A, Björck I, Nyman M. (2007). "Dietary
supplementation with beta-glucan enriched oat bran increases faecal concentration of
carboxylic acids in healthy subjects." european journal of clinical nutrition ahead of
print.
Nutra USA. (2007). "National Cancer Institute funds study using Beneo." from
http://www.nutraingredients-usa.com/news/ng.asp?n=77844-orafti-national-cancerinstitute-beneo.
Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, Ohnuma T,
Matsushita S.. (2007). "Soy product consumption and the risk of colon cancer: a
prospective study in takayama, Japan." Nutritional Cancer 57(2): 151-7.
O'Keefe, Stephen J. D., Dan Chung, Nevine Mahmoud, Antonia R. Sepulveda,
Mashudu Manafe, Judith Arch, Haytham Adada and Tian van der Merwe (2007). "Why
do African Americans get more colon cancer than native Africans?" Journal of Nutrition
137(1, Suppl. S): 175S-182S.
Rafter, Joseph, Michael Bennett, Giovanna Caderni, Yvonne Clune, Roisin Hughes,
Pernilla C. Karlsson, Annett Klinder, Micheal O'Riordan, Gerald C. O'Sullivan, Beatrice
Pool-Zobel, Gerhard Rechkemmer, Monika Roller, Ian Rowland, Maddalena Salvadori,
Herbert Thijs, Jan Van Loo, Bernhard Watzl and John K. Collins (2007). "Dietary
synbiotics reduce cancer risk factors in polypectomized and colon cancer patients."
American Journal of Clinical Nutrition 85(2): 488-496.
Schatzkin A, Mouw T, Park Y, Subar AF, Kipnis V, Hollenbeck A, Leitzmann MF,
Thompson FE. (2007). "Dietary fiber and whole-grain consumption in relation to
colorectal cancer in the NIH-AARP Diet and Health Study." american journal of clinical
nutrition 85(5): 1353-60.
Emerging Issues 32
Stoner GD, Wang LS, Zikri N, Chen T, Hecht SS, Huang C, Sardo C, Lechner JF.
(2007). "Cancer prevention with freeze-dried berries and berry components." Seminar
cancer Biology ahead of print.
Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy
(2007). "Tomato lycopene extract supplementation decreases insulin-like growth factor-I
levels in colon cancer patients." European journal of cancer prevention 16(4): 298-303.
Prostate Cancer, Diet, & Nutrition
Alvarez-León EE, Román-Viñas B, Serra-Majem L. (2006). "Dairy products and health:
a review of the epidemiological evidence." The British Journal of Nutrition
96(supplement 1): s94-99.
Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. (2007). "Fruit, vegetable,
vitamin A intakes, and prostate cancer risk." Prostate Cancer Prostatic ahead of print.
Berquin IM, Min Y, Wu R, Wu J, Perry D, Cline JM, Thomas MJ, Thornburg T, Kulik G,
Smith A, Edwards IJ, D'Agostino R, Zhang H, Wu H, Kang JX, Chen YQ. (2007).
"Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids." jour.
clin. invest 117(7): 1866-1875.
Bostonnews.com. (2007, july-9). "does Lycopene in tomatoes help prevent prostate
cancer?" from
http://www.boston.com/news/globe/health_science/articles/2007/07/09/does_the_lycope
ne_in_tomatoes_help_prevent_prostate_cancer/.
Centers for Disease Control. (2007). "2007 prostate data." from
http://www.cdc.gov/cancer/prostate/prospdf/0607_prostate_fs.pdf.
Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J. (2007). "A Prospective
Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk." Cancer
Epidemiology And Biomarkers & prevention ahead of print.
Demark-Wahnefried W, Clipp EC, Lipkus IM, Lobach D, Snyder DC, Sloane R,
Peterson B, Macri JM, Rock CL, McBride CM, Kraus WE. (2007). "Main outcomes of the
FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention
among breast and prostate cancer survivors." journal of clinical oncology 25(19): 27092718.
Eriksson M, Wedel H, Wallander MA, Krakau I, Hugosson J, Carlsson S, Svärdsudd K.
(2007). "The impact of birth weight on prostate cancer incidence and mortality in a
population-based study of men born in 1913 and followed up from 50 to 85 years of
age." prostate 67(11): 1247-54.
Emerging Issues 33
Gao X, LaValley MP, Tucker KL. (2005). "Prospective studies of dairy product and
calcium intakes and prostate cancer risk: a meta-analysis." Journal of the National
Cancer Institute 97(23): 1768-77.
Giovannucci E, Liu Y, Stampfer MJ, Willett WC. (2006). "A prospective study of calcium
intake and incident and fatal prostate cancer." Cancer Epidemiology And Biomarkers &
prevention 15(2): 203-210.
Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC.
(2006). "Prospective study of predictors of vitamin D status and cancer incidence and
mortality in men." Journal of the National Cancer Institute 98(7): 451-459.
Grant, WB. (2006). "Epidemiology of disease risks in relation to vitamin D insufficiency."
Progess in Biophysics and molecular biology 92(1): 65-79.
Hoption Cann SA, Qiu Z, van Netten C. (2007). "A Prospective Study of Iodine Status,
Thyroid Function, and Prostate Cancer Risk: Follow-up of the First National Health and
Nutrition Examination Survey." nutrition and cancer 58(1): 28-34.
Kirsh VA, Hayes RB, Mayne ST, Chatterjee N, Subar AF, Dixon LB, Albanes D,
Andriole GL, Urban DA, Peters U (2006). "Supplemental and dietary vitamin E, betacarotene, and vitamin C intakes and prostate cancer risk." Journal of the National
Cancer Institute 98(4): 245-54.
Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA,
Crawford ED, Hayes RB. (2006). "A prospective study of lycopene and tomato product
intake and risk of prostate cancer." Cancer Epidemiology And Biomarkers & prevention
15(1): 92-98.
Negri E, Bertuccio P, Talamini R, Franceschi S, Montella M, Giacosa A, Pelucchi C, La
Vecchia C. (2006). "A history of cancer in the husband does not increase the risk of
breast cancer." International Journal of Cancer: 118(12): 3177-3179.
Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King I, Thornquist M, Goodman
G. (2007). "(n-6) PUFA Increase and Dairy Foods Decrease Prostate Cancer Risk in
Heavy Smokers." Journal of Nutrition 137(7): 1821-1827.
Stroup SP, Cullen J, Auge BK, L'esperance JO, Kang SK (2007). "Effect of obesity on
prostate-specific antigen recurrence after radiation therapy for localized prostate cancer
as measured by the 2006 Radiation Therapy Oncology Group-American Society for
Therapeutic Radiation and Oncology (RTOG-ASTRO) Phoenix consensus definition."
Cancer PMID: 17614338 [PubMed - as supplied by publisher]: Hasnt been printed
yet.
Emerging Issues 34
Sun M, Ma L. (2006). "Treatments of exceptionally large prostate cancer patients with
low-energy intensity-modulated photons." journal of applied clinical medical physics
7(4): 43-9.
Szkudelska K, Nogowski L. (2007). "Genistein-A dietary compound inducing hormonal
and metabolic changes." Journal of Steroid biochemical molecular biology ahead of
pring.
Weinstein SJ, Wright ME, Lawson KA, Snyder K, Männistö S, Taylor PR, Virtamo J,
Albanes D. (2007). "Serum and dietary vitamin E in relation to prostate cancer risk."
cancer Epidemiology And Biomarkers & prevention 16(6): 1253-9.
Werny DM, Thompson T, Saraiya M, Freedman D, Kottiri BJ, German RR, Wener M.
(2007). "Obesity is negatively associated with prostate-specific antigen in U.S. men,
2001-2004." cancer Epidemiology And Biomarkers & prevention 16(1): 70-76.
Wicht A, Hamza A, Loertzer H, Dietl M, Heynemann H, Fornara P. (2006). "[Diagnostics
and treatment of prostate cancer after kidney transplantation]." Urologe A. 45(1): 32-37.
Emerging Issues 35
Personal Care Products
Andrew, A. S., A. R. Schned, et al. (2004). "Bladder cancer risk and personal hair dye
use." Int J Cancer 109(4): 581-6.
Donovan, M., C. M. Tiwary, D. Axelrod, A. J. Sasco, L. Jones, R. Hajek, E. Sauber, J.
Kuo and D. L. Davis (2007). "Personal care products that contain estrogens or
xenoestrogens may increase breast cancer risk." Med Hypotheses 68(4): 756-66.
Exley, C., L. M. Charles, L. Barr, C. Martin, A. Polwart and P. D. Darbre (2007).
"Aluminium in human breast tissue." J Inorg Biochem.
Karagas, Margaret R., Virginia A. Stannard, Leila A. Mott, Mary Jo Slattery, Steven K.
Spencer and Martin A. Weinstock (2002). "Use of Tanning Devices and Risk of Basal
Cell and Squamous Cell Skin Cancers." J. Natl. Cancer Inst. 94(3): 224-226.
Kleinsasser, N. H., E. R. Kastenbauer, et al. (2000). "Phthalates demonstrate
genotoxicity on human mucosa of the upper aerodigestive tract." Environmental and
Molecular Mutagenesis 35(1): 9-12.
Van Landingham, C. B., G. A. Lawrence and A. M. Shipp (2004). "Estimates of lifetimeabsorbed daily doses from the use of personal-care products containing polyacrylamide:
a Monte Carlo analysis." Risk Anal 24(3): 603-19.
Wierik, E. J., P. T. Hendricks and M. Boerstoel-Streefland (2004). "Clinical background
of women prescribed tibolone or combined estrogen + progestogen therapies: a UK
MediPlus study." Climacteric 7(2): 197-209.
Emerging Issues 36
SECTION B: PREVENTION AND EARLY DETECTION
Emerging Issues 37
Healthcare Access
Abenhaim, H. A., L. Titus-Ernstoff and D. W. Cramer (2007). "Ovarian cancer risk in
relation to medical visits, pelvic examinations and type of health care provider." Cmaj
176(7): 941-7.
Bradley CJ, Given CW, Dahman B, Luo Z, Virnig BA. (2007- May). "Diagnosis of
advanced cancer among elderly Medicare and Medicaid patients." Medical Care 45(5):
410-419.
Carney, Patricia A., Joyce P. Yi, Linn A. Abraham, Diana L. Miglioretti, Erin J. Aiello,
Martha S. Gerrity, Lisa Reisch, Eric A. Berns, Edward A. Sickles and Joann G. Elmore
(2007). "Reactions to Uncertainty and the Accuracy of Diagnostic Mammography."
JGIM: Journal of General Internal Medicine 22(2): 234-241.
Crew, K. D., A. I. Neugut, X. Wang, J. S. Jacobson, V. R. Grann, G. Raptis and D. L.
Hershman (2007). "Racial disparities in treatment and survival of male breast cancer." J
Clin Oncol 25(9): 1089-98.
Dietrich, A. J., J. N. Tobin, A. Cassells, C. M. Robinson, M. A. Greene, C. H. Sox, M. L.
Beach, K. N. DuHamel and R. G. Younge (2006). "Telephone care management to
improve cancer screening among low-income women: a randomized, controlled trial."
Ann Intern Med 144(8): 563-71.
Elmore, J. G., S. H. Taplin, W. E. Barlow, G. R. Cutter, C. J. D'Orsi, R. E. Hendrick, L.
A. Abraham, J. S. Fosse and P. A. Carney (2005). "Does litigation influence medical
practice? The influence of community radiologists' medical malpractice perceptions and
experience on screening mammography." Radiology 236(1): 37-46.
Fung-Kee-Fung, M., M. Brouwers, T. K. Oliver and B. Rosen (2007). "Health care use
and risk of ovarian cancer: is there a link?" Cmaj 176(7): 949-50.
Gee, G. C., A. Ryan, D. J. Laflamme and J. Holt (2006). "Self-reported discrimination
and mental health status among African descendants, Mexican Americans, and other
Latinos in the New Hampshire REACH 2010 Initiative: the added dimension of
immigration." Am J Public Health 96(10): 1821-8.
Harper, Diane M., Megan M. Moncur, William H. Harper, Gregory C. Burke, Cynthia A.
Rasmussen and Margaret C. Mumford (2000). "The Technical Performance and Clinical
Feasibility of Telecolposcopy." Journal of Family Practice 49(7): 623-627.
Homa, K. (2004). "A conceptual idea to improve access in a complex health care
system." Quality Management in Health Care 13(4): 243-263.
Emerging Issues 38
Kerlikowske, K., P. A. Carney, B. Geller, M. T. Mandelson, S. H. Taplin, K. Malvin, V.
Ernster, N. Urban, G. Cutter, R. Rosenberg and R. Ballard-Barbash (2000).
"Performance of screening mammography among women with and without a firstdegree relative with breast cancer." Ann Intern Med 133(11): 855-63.
Kieran, S., L. J. Loescher and K. H. Lim (2007). "The role of financial factors in
acceptance of clinical BRCA genetic testing." Genet Test 11(1): 101-10.
New Hampshire Advisory Committee to the United States Commission on Civil Rights
(2005). Language and Access to Health Care: Easing Barriers in New Hampshire: 35.
Ross JS, Bernheim SM, Bradley EH, Teng HM, Gallo WT. (2007). "Use of preventive
care by the working poor in the United States." Preventitive medicine 44(3): 254-259.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Health Care Access. Nancy Ryan. Lee, NH, New Hampshire Breast
Cancer Coalition.
Emerging Issues 39
Breast and Cervical Cancer
General
Dietrich, A. J., J. N. Tobin, et al. (2006). "Telephone care management to improve
cancer screening among low-income women: a randomized, controlled trial." Ann Intern
Med 144(8): 563-71.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Knowing Risk Factors and Imaging. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
Titus-Ernstoff, L., A. N. Tosteson, C. Kasales, J. Weiss, M. Goodrich, E. E. Hatch and
P. A. Carney (2006). "Breast cancer risk factors in relation to breast density (United
States)." Cancer Causes Control 17(10): 1281-90.
Meissner, Helen I., Robert A. Smith, Barbara K. Rimer, Katherine M. Wilson, William
Rakowski, Sally W. Vernon and Peter A. Briss (2004). "Promoting cancer screening:
Learning from experience." Cancer 101(S5): 1107-1117.
New Hampshire Department of Health & Human Services. (2007). "Breast and Cervical
Cancer Program." from http://www.dhhs.state.nh.us/DHHS/CDPC/bccp.htm.
Cervical Cancer Prevention and Screening
Associated Press. (2006, November 30, 2006). "N.H. first state to offer girls free cancer
vaccine." Associated Press Retrieved June 2, 2007, 2007, from
http://www.msnbc.msn.com/id/15958573/.
Balluz, L., I. B. Ahluwalia, et al. (2004). "Surveillance for certain health behaviors among
selected local areas--United States, Behavioral Risk Factor Surveillance System, 2002."
MMWR Surveill Summ 53(5): 1-100.
Burak, L. J. and M. Meyer (1997). "Using the Health Belief Model to examine and
predict college women's cervical cancer screening beliefs and behavior." Health Care
Women Int 18(3): 251-62.
Carney, P., A. J. Dietrich, et al. (1992). "Improving future preventive care through
educational efforts at a women's community screening program." J Community Health
17(3): 167-74.
Carney, P., A. J. Dietrich, et al. (1992). "Improving future preventive care through
educational efforts at a women's community screening program." J Community Health
17(3): 167-74.
Emerging Issues 40
Dietrich, A. J., P. Carney-Gersten, et al. (1989). "Community screening for cervical
cancer in New Hampshire." J Fam Pract 29(3): 319, 321, 323.
Dietrich, A. J., J. N. Tobin, et al. (2006). "Telephone care management to improve
cancer screening among low-income women: a randomized, controlled trial." Ann Intern
Med 144(8): 563-71.
Harper, D., E. Franco, et al. (2006). "Sustained efficacy up to 4.5 years of a bivalent L1
virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from
a randomised control trial." Lancet 267(9518): 1247-1255.
Harper, D. M., M. M. Moncur, et al. (2000). "The technical performance and clinical
feasibility of telecolposcopy." J Fam Pract 49(7): 623-7.
Harper, D. M., K. M. Parke, et al. (2000). "Self-reported desire to improve colposcopic
impressions." Arch Gynecol Obstet 264(3): 137-42.
Mount, S. L. and J. L. Papillo (1999). "A study of 10,296 pediatric and adolescent
Papanicolaou smear diagnoses in northern New England." Pediatrics 103(3): 539-45.
New Hampshire Department of Health & Human Services. (2007). "Breast and Cervical
Cancer Program." from http://www.dhhs.state.nh.us/DHHS/CDPC/bccp.htm.
Sirovich, B. E., D. J. Gottlieb, et al. (2003). "The burden of prevention: downstream
consequences of Pap smear testing in the elderly." J Med Screen 10(4): 189-95.
Genetic Testing
Fu, R., E. L. Harris, et al. (2007). "Estimating risk of breast cancer in carriers of BRCA1
and BRCA2 mutations: a meta-analytic approach." Stat Med 26(8): 1775-87.
Kenen, R. H., P. J. Shapiro, et al. (2007). "Peer-support in coping with medical
uncertainty: discussion of oophorectomy and hormone replacement therapy on a webbased message board." Psychooncology.
Kieran, S., L. J. Loescher, et al. (2007). "The role of financial factors in acceptance of
clinical BRCA genetic testing." Genet Test 11(1): 101-10.
McBride, D. (2007). "Test to Predict Breast Cancer Relapse Approved by FDA." ONS
Connect 22(5): 7-7.
Moller, P., D. G. Evans, et al. (2007). "Surveillance for familial breast cancer:
Differences in outcome according to BRCA mutation status." Int J Cancer 121(5): 101720.
Emerging Issues 41
Nisker, J. A. (2007). "The Need for Public Education: "Surveillance and Risk Reduction
Strategies" for Women at Risk for Carrying BRCA Gene Mutations." J Obstet Gynaecol
Can 29(6): 510-1.
Pal, T., J. Permuth-Wey, et al. (2007). "Improved survival in BRCA2 carriers with
ovarian cancer." Fam Cancer 6(1): 113-9.
Rennert, G., S. Bisland-Naggan, et al. (2007). "Clinical outcomes of breast cancer in
carriers of BRCA1 and BRCA2 mutations." N Engl J Med 357(2): 115-23.
Robson, M. (2007). "Is breast conservation a reasonable option for women with BRCAassociated breast cancer?" Nat Clin Pract Oncol 4(1): 10-1.
Sivell, S., R. Iredale, et al. (2007). "Cancer genetic risk assessment for individuals at
risk of familial breast cancer." Cochrane Database Syst Rev(2): CD003721.
Vidarsdottir, L., S. K. Bodvarsdottir, et al. (2007). "Breast cancer risk associated with
AURKA 91T -->A polymorphism in relation to BRCA mutations." Cancer Lett 250(2):
206-12.
Weitzel, J. N., V. I. Lagos, et al. (2007). "Limited family structure and BRCA gene
mutation status in single cases of breast cancer." JAMA 297(23): 2587-95.
Imaging
Akin, O., S. Mironov, et al. (2007). "Imaging of uterine cancer." Radiol Clin North Am
45(1): 167-82.
Bartella, L., C. S. Smith, et al. (2007). "Imaging breast cancer." Radiol Clin North Am
45(1): 45-67.
Brooksby, B, BW Pogue, S Jiang, H Dehghani, S Srinivasan, C Kogel, TD Tosteson, J
Weaver, SP Poplack and KD Paulsen (2006). "Imaging breast adipose and
fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared
spectral tomography." Proc Natl Acad Sci U S A. 103(23): 8828-33.
Carney, P. A., M. E. Goodrich, D. M. O'Mahony, A. N. Tosteson, M. S. Eliassen, S. P.
Poplack, S. Birnbaum, B. G. Harwood, K. A. Burgess, B. T. Berube, W. S. Wells, J. P.
Ball and M. M. Stevens (2000). "Mammography in New Hampshire: characteristics of
the women and the exams they receive." J Community Health 25(3): 183-98.
Carney, P. A., M. E. Goodrich, et al. (2005). "Utilization of screening mammography in
New Hampshire: a population-based assessment." Cancer 104(8): 1726-32.
Carney, P. A., C. J. Kasales, A. N. Tosteson, J. E. Weiss, M. E. Goodrich, S. P.
Poplack, W. S. Wells and L. Titus-Ernstoff (2004). "Likelihood of additional work-up
Emerging Issues 42
among women undergoing routine screening mammography: the impact of age, breast
density, and hormone therapy use." Prev Med 39(1): 48-55.
Carney, P. A., C. J. Kasales, et al. (2004). "Likelihood of additional work-up among
women undergoing routine screening mammography: the impact of age, breast density,
and hormone therapy use." Prev Med 39(1): 48-55.
Carney, P. A., D. L. Miglioretti, et al. (2003). "Individual and combined effects of age,
breast density, and hormone replacement therapy use on the accuracy of screening
mammography." Ann Intern Med 138(3): 168-75.
Carpenter, C. M., B. W. Pogue, et al. (2007). "Image-guided optical spectroscopy
provides molecular-specific information in vivo: MRI-guided spectroscopy of breast
cancer hemoglobin, water, and scatterer size." Opt Lett 32(8): 933-5.
D'Orsi, C., S. P. Tu, et al. (2005). "Current realities of delivering mammography services
in the community: do challenges with staffing and scheduling exist?" Radiology 235(2):
391-5.
Egger, J. R., G. R. Cutter, et al. (2005). "Mammographers' perception of women's
breast cancer risk." Med Decis Making 25(3): 283-9.
Elmore, J. G., S. H. Taplin, et al. (2005). "Does litigation influence medical practice?
The influence of community radiologists' medical malpractice perceptions and
experience on screening mammography." Radiology 236(1): 37-46.
Emro, Robert (2004) UNH chemists invent molecules for cancer imaging: “Clamshell”
could allow earlier tumor detection with PET scans UNH College of Engineering
and Physical Sciences
Hendrick, R. E., G. R. Cutter, et al. (2005). "Community-based mammography practice:
services, charges, and interpretation methods." AJR Am J Roentgenol 184(2): 433-8.
Jefford, M. (2006). "Factors associated with interval adherence to mammography
screening in a population-based sample of New Hampshire women." Cancer 106(9):
2084-5.
Li, D., P. M. Meaney, et al. (2003). "Comparisons of three alternative breast modalities
in a common phantom imaging experiment." Med Phys 30(8): 2194-205.
Meaney, P., M. Fanning, et al. (2007). "Initial clinical experience with microwave breast
imaging in women with normal mammography." Acad Radiol 14(2): 207-218.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Knowing Risk Factors and Imaging. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
Emerging Issues 43
Sprague, Jennifer E., Yijie Peng, Xiankai Sun, Gary R. Weisman, Edward H. Wong,
Samuel Achilefu and Carolyn J. Anderson (2004). "Preparation and Biological
Evaluation of Copper-64–Labeled Tyr3-Octreotate Using a Cross-Bridged Macrocyclic
Chelator " Clinical Cancer Research 10: 8674-8682.
Emerging Issues 44
Prostate Cancer Screening
American Urologic Association. "Prostate Cancer Checklist." Retrieved July 1, 2007,
from http://www.healthcentral.com/prostate/prostate-check-3075-143.html.
Bangma, CH, S Roemeling and FH Schröder (2007, March). "Overdiagnosis and
overtreatment of early detected prostate cancer." World Journal of Urology 25(1): 3-9.
Centers for Disease Control. (2007). "2007 prostate data." from
http://www.cdc.gov/cancer/prostate/prospdf/0607_prostate_fs.pdf.
Chuang AY, Chang SJ, Horng CF, Tsou MH. (2007- May). "Study of prostate cancer
pathologic features in Chinese populations." Urology 69(5): 915-920.
Frydenberg M, Wijesinha S. (May 2007). "Diagnosing prostate cancer - what GPs need
to know." Austrailian Family Physician 36(5): 345-347.
Gennari R, Veronesi U, Andreoli C, Betka J, Castelli A, Gatti G, Hugosson J, Llovet JM,
Melia J, Nakhosteen JA, Pastorino U, Sideri M, Stephan C, Veronesi P, Zurrida S.
(2007). "Early detection of cancer: ideas for a debate." critical reviews in
oncology/hematology 61(2): 97-103.
Graif T, Loeb S, Roehl KA, Gashti SN, Griffin C, Yu X, Catalona WJ. (2007). "Under
diagnosis and over diagnosis of prostate cancer." journal of Urology 178(1): 88-92.
Greco, K. (2006). "Cancer screening in older adults in an era of genomics and
longevity." Seminars in Oncology Nursing 22(1): 10-19.
Guerra CE, Jacobs SE, Holmes JH, Shea JA. (2007). "Are physicians discussing
prostate cancer screening with their patients and why or why not? A pilot study." journal
of general medicine 22(7): 901-7.
Hoffman RM, Denberg T, Hunt WC, Hamilton AS. (2007). "Prostate Cancer Testing
following a Negative Prostate Biopsy: Over Testing the Elderly." Journal of Gene
Medicine ahead of print.
Hughes Halbert C, Barg FK, Weathers B, Delmoor E, Coyne J, Wileyto EP, Arocho J,
Mahler B, Malkowicz SB. (2007). "Differences in cultural beliefs and values among
african american and European american men with prostate cancer." Cancer Control
14(3): 277-284.
Katz DA, Jarrard DF, McHorney CA, Hillis SL, Wiebe DA, Fryback DG. (2007). "Health
perceptions in patients who undergo screening and workup for prostate cancer."
Urology 69(2): 215-220.
Emerging Issues 45
Keefe, Diane. (2007). "Study Identifies characteristics of clinicians likely to order
inappropriate prostate screenings." from http://www.eurekalert.org/pub_releases/200707/jaaj-sic070507.php.
Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA,
Crawford ED, Hayes RB. (2006). "A prospective study of lycopene and tomato product
intake and risk of prostate cancer." Cancer Epidemiology And Biomarkers & prevention
15(1): 92-98.
Lessick, M and A. Katz (2006-DEC). "A genetics perspective on prostate cancer."
Urologic nursing: official journal of the American Urology association allied. 26(6): 454460.
Marcella S, Delnevo CD, Coughlin SS. (2007). "A national survey of medical students'
beliefs and knowledge in screening for prostate cancer." Journal of General internal
medicein 22(1): 80-85.
Markushin Y, Gaikwad N, Zhang H, Kapke P, Rogan EG, Cavalieri EL, Trock BJ,
Pavlovich C, Jankowiak R. (2006). "Potential biomarker for early risk assessment of
prostate cancer." Prostate 66(14): 1565-1571.
McFall, SL. (2006). "US men discussing prostate-specific antigen tests with a
physician." Annals of family medicine 4(5): 433-436.
Morgan VA, Kyriazi S, Ashley SE, Desouza NM. (2007). "Evaluation of the potential of
diffusion-weighted imaging in prostate cancer detection." Acta Radiology 48(6): 695703.
Moul JW, Sun L, Hotaling JM, Fitzsimons NJ, Polascik TJ, Robertson CN, Dahm P,
Anscher MS, Mouraviev V, Pappas PA, Albala DM. (2007). "Age adjusted prostate
specific antigen and prostate specific antigen velocity cut points in prostate cancer
screening." Journal of Urology 177(2): 499-503.
Oliffe, J and S Thorne (2007- Feb). "Men, masculinities, and prostate cancer: Australian
and Canadian patient perspectives of communication with male physicians." Qualitative
Health Research 17(2): 149-161.
Pickles T, Ruether JD, Weir L, Carlson L, Jakulj F (2007). "Psychosocial barriers to
active surveillance for the management of early prostate cancer and a strategy for
increased acceptance." BJU international ahead of print.
Platz, EA, MF Leitzmann, K Visvanathan, EB Rimm, MJ Stampfer, WC Willett and E
Giovannucci (2006-DEC). "Statin drugs and risk of advanced prostate cancer." J Natl
Cancer Inst.
Emerging Issues 46
Reinberg, Steven. (2007). "Many Men Getting Unnecessary Prostate Cancer Blood
Tests." from
http://news.yahoo.com/s/hsn/20070709/hl_hsn/manymengettingunnecessaryprostateca
ncerbloodtests.
Ross LE, Richardson LC, Berkowitz Z. (2006). "The effect of physician-patient
discussions on the likelihood of prostate-specific antigen testing." journal of the national
medical association 98(11): 1823-1829.
Schnur JB, DiLorenzo TA, Montgomery GH, Erblich J, Winkel G, Hall SJ, Bovbjerg DH.
(2006). "Perceived risk and worry about prostate cancer: a proposed conceptual
model." behavioral medicine 32(3): 89-96.
Stephenson AJ, Kuritzky L, Campbell SC. (2007). "Screening for urologic malignancies
in primary care: pros, cons, and recommendations." cleveland clinic journal of medicine
74 (supplement 3:s6-7).
Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, Feng Z,
Parnes HL, Coltman CA. (2006). "Assessing prostate cancer risk: results from the
Prostate Cancer Prevention Trial." Journal of the National Cancer Institute 19(98): 529534.
Wicht A, Hamza A, Loertzer H, Dietl M, Heynemann H, Fornara P. (2006). "[Diagnostics
and treatment of prostate cancer after kidney transplantation]." Urologe A. 45(1): 32-37.
Emerging Issues 47
Colorectal Screening
CDC. (2005). "Colorectal screening and prevention information." from
http://www.cdc.gov/cancer/colorectal/statistics/screening_rates.htm.
CDC. (2007). "COLORECTAL CANCER INITIATIVES." from
http://www.cdc.gov/cancer/colorectal/pdf/0607_colorectal_fs.pdf.
Colorectal Cancer Coalition. (2007). "State Updates for New Hampshire ", from
http://www.fightcolorectalcancer.org/advocacy/2007/04/state_updates_from_california.p
hp.
Driver, Jane A., J. Michael Gaziano, Rebecca P. Gelber, I. Min Lee, Julie E. Buring and
Tobias Kurth (2007). "Development of a risk score for colorectal cancer in men."
American Journal of Medicine 120(3): 257-263.
Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, Lamerz R,
Peltomaki P, Sturgeon C, Topolcan O. (2007). "Tumour markers in colorectal cancer:
European Group on Tumour Markers (EGTM) guidelines for clinical us." European
journal of cancer 43(9): 1348-1360.
Friedman, M and ML. Borum (2007). "Colon cancer screening consultations may
identify racial disparity in hypertension diagnosis and management." J Natl Med Assoc.
99(5): 525-526.
Greco, K. (2007). "Caring for patients at risk for hereditary colorectal cancer." Oncology
21((2 Suppl Nurse Ed):): 29-38; discussion 39.
Greiner, K. Allen, Wendi Born, Nicole Nollen and Jasjit S. Ahluwalia (2005). "Knowledge
and Perceptions of Colorectal Cancer Screening Among Urban African Americans."
Journal of General Internal Medicine 20(11): 977-983.
Gross, Cary P., Martin S. Andersen, Harlan M. Krumholz, Gail J. McAvay, Deborah
Proctor and Mary E. Tinetti (2006). "Relation between Medicare screening
reimbursement and stage at diagnosis for older patients with colon cancer." JAMA
(Journal of the American Medical Association) 296(23): 2815-2822.
Kohut K, Manno M, Gallinger S, Esplen MJ. (2007). "Should healthcare providers have
a duty to warn family members of individuals with an HNPCC-causing mutation? A
survey of patients from the Ontario Familial Colon Cancer Registry." Journal of Medical
genetics 44(6): 404-7.
Latimes.org. (2007). "New Colon Test Promising." from
http://www.latimes.com/news/science/la-na-colon6jul06,1,2357058.story?track=rss.
Emerging Issues 48
Menon U, Belue R, Sugg Skinner C, Rothwell BE, Champion V. (2007). "Perceptions of
colon cancer screening by stage of screening test adoption." Cancer Nursing 30(3):
178-85.
Pasetto, LM and S. Monfardini (2007). "Colorectal cancer screening in elderly patients:
When should be more useful?" Cancer treatment and prevention ahead of print.
Shenson, Douglass, Julie Bolen, Mary Adams, Laura Seef and Donald Blackman
(2005). "Are Older Adults Up-To-Date with cancer screening and vaccinations."
Preventing Chronic Disease 2 No:3.
Walsh, Judith (2005). "Colorectal Cancer Screening. The Time Is Now!" Journal of
General Internal Medicine 20(11): 1068-1070.
Young WF, McGloin J, Zittleman L, West DR, Westfall JM. (2007). "Predictors of
colorectal screening in rural colorado: testing to prevent colon cancer in the high plains
research network." Journal of Rural health 23(3): 238-45.
Emerging Issues 49
SECTION C: TREATMENT AND SURVIVORSHIP
Emerging Issues 50
Radiation and Chemotherapy
Ahles, T. A., A. J. Saykin, C. T. Furstenberg, B. Cole, L. A. Mott, K. Skalla, M. B.
Whedon, S. Bivens, T. Mitchell, E. R. Greenberg and P. M. Silberfarb (2002).
"Neuropsychologic impact of standard-dose systemic chemotherapy in long-term
survivors of breast cancer and lymphoma." J Clin Oncol 20(2): 485-93.
Bangalore, M., S. Matthews and M. Suntharalingam (2007). "Recent advances in
radiation therapy for head and neck cancer." ORL J Otorhinolaryngol Relat Spec 69(1):
1-12.
Calabro, F. and C. N. Sternberg (2007). "Current indications for chemotherapy in
prostate cancer patients." Eur Urol 51(1): 17-26.
Conti, F., D. Sergi, P. Foggi, M. I. Abbate and M. Lopez (2007). "[New combination
chemotherapy regimens in the primary treatment of operable breast cancer]." Clin Ter
158(1): 55-75.
Crivellari, G., S. Monfardini, S. Stragliotto, D. Marino and S. M. Aversa (2007).
"Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to
megadoses." Oncologist 12(1): 79-89.
Dignam, James J., Blase N. Polite, Greg Yothers, Peter Raich, Linda Colangelo,
Michael J. O'Connell and Norman Wolmark (2006). "Body mass index and outcomes in
patients who receive adjuvant chemotherapy for colon cancer." Journal of the National
Cancer Institute (Cary) 98(22): 1647-1654.
Dupertuis YM, Meguid MM, Pichard C. (2007). "Colon cancer therapy: new perspectives
of nutritional manipulations using polyunsaturated fatty acids." Current opinions in
nutritional metabolic care 10(4): 427-32.
Farquhar, C. M., J. Marjoribanks, A. Lethaby and R. Basser (2007). "High dose
chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis."
Cancer Treat Rev 33(4): 325-37.
Gross CP, McAvay GJ, Guo Z, Tinetti ME. (2007). "The impact of chronic illnesses on
the use and effectiveness of adjuvant chemotherapy for colon cancer." Cancer 109(12):
2410-9.
Goyal, S., T. Kearney and B. G. Haffty (2007). "Current application and research
directions for partial-breast irradiation." Oncology (Williston Park) 21(4): 449-61;
discussion 461-2, 464, 470.
Emerging Issues 51
Hwang, J. J. (2007). "Role of chemotherapy in the treatment of gastroesophageal
cancers." Oncology (Williston Park) 21(5): 579-86; discussion 587, 591-2.
Maracic, Lindy and Joanne Van Nostrand (2007). "Anesthetic implications for cancer
chemotherapy." AANA Journal 75(3): 219-226.
Meissner, Helen I., Robert A. Smith, Barbara K. Rimer, Katherine M. Wilson, William
Rakowski, Sally W. Vernon and Peter A. Briss (2004). "Promoting cancer screening:
Learning from experience." Cancer 101(S5): 1107-1117.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Reassessing Anthracycline-Based Chemotherapy Treatment.
Nancy Ryan. Lee, NH, New Hampshire Breast Cancer Coalition.
Quah HM, Joseph R, Schrag D, Shia J, Guillem JG, Paty PB, Temple LK, Wong WD,
Weiser MR. (2007). "Young Age Influences Treatment but not Outcome of Colon
Cancer." Ann Surg oncol 26(ahead of print).
Reddy, BS. (2007). "Strategies for colon cancer prevention: combination of
chemopreventive agents." Sub-cellular biochemistry 42: 213-25.
Rendi, M. H., N. Suh, W. W. Lamph, S. Krajewski, J. C. Reed, R. A. Heyman, A.
Berchuck, K. Liby, R. Risingsong, D. B. Royce, C. R. Williams and M. B. Sporn (2004).
"The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268
cooperate to promote transforming growth factor beta-dependent apoptosis in breast
cancer." Cancer Res 64(10): 3566-71.
Riker, A. I., S. Radfar, S. Liu, Y. Wang and H. T. Khong (2007). "Immunotherapy of
melanoma: a critical review of current concepts and future strategies." Expert Opin Biol
Ther 7(3): 345-58.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Reassessing Anthracycline-Based Chemotherapy Treatment. Nancy
Ryan. Lee, NH, New Hampshire Breast Cancer Coalition.
Savellano, M. D., B. W. Pogue, P. J. Hoopes, E. S. Vitetta and K. D. Paulsen (2005).
"Multiepitope HER2 targeting enhances photoimmunotherapy of HER2-overexpressing
cancer cells with pyropheophorbide-a immunoconjugates." Cancer Res 65(14): 6371-9.
Schneider, SM and LE. Hood (2007). "Virtual reality: a distraction intervention for
chemotherapy." Oncology nursing Forum 34(1): 39-46.
Sowery RD, So AI, Gleave ME. (2007). "Therapeutic options in advanced prostate
cancer: present and future." Current Urology Reports 8(1): 53-59.
Emerging Issues 52
Tanner, Lindsey. (2007). "Study: Chemotherapy plus surgery helps colon cancer that
has spread to liver." Fosters Online Retrieved Sunday-June-12, from
http://www.fosters.com/apps/pbcs.dll/article?AID=/20070610/FOSTERS01/106050327/1/SPNEWS02.
Warren, A. J., D. J. Mustra and J. W. Hamilton (2001). "Detection of mitomycin C-DNA
adducts in human breast cancer cells grown in culture, as xenografted tumors in nude
mice, and in biopsies of human breast cancer patient tumors as determined by (32)Ppostlabeling." Clin Cancer Res 7(4): 1033-42.
www.stuff.co. (2007). "Prostate cancer-the quiet killer." from
http://www.stuff.co.nz/4121925a20475.html.
Yoo, J and YJ. Lee (2007). "Effect of hyperthermia and chemotherapeutic agents on
TRAIL-induced cell death in human colon cancer cells." Journal of Cell Biochemistry
ahead of print.
Zalcman, G., N. Richard and E. Bergot (2007). "[New biological treatments for lung
cancer]." Rev Pneumol Clin 63(1): 20-8.
Emerging Issues 53
Surgery
Aletti, G. D., M. M. Gallenberg, W. A. Cliby, A. Jatoi and L. C. Hartmann (2007).
"Current management strategies for ovarian cancer." Mayo Clin Proc 82(6): 751-70.
Black, C., J. Marotti, E. Zarovnaya and J. Paydarfar (2006). "Critical evaluation of frozen
section margins in head and neck cancer resections." Cancer 107(12): 2792-2800.
Castillo, M. D. and P. M. Heerdt (2007). "Pulmonary resection in the elderly." Curr Opin
Anaesthesiol 20(1): 4-9.
Carney, P. A., M. S. Eliassen, W. A. Wells and W. G. Swartz (1998). "Can we improve
breast pathology reporting practices? A community-based breast pathology quality
improvement program in New Hampshire." J Community Health 23(2): 85-98.
Chok, KS and WL. Law (2007). "Prognostic Factors Affecting Survival and Recurrence
of Patients with pT1 and pT2 Colorectal Cancer." World journal of surgery 31(7): 148590.
Collins, E. D., C. L. Kerrigan and P. Anglade (1999). "Surgical treatment of early breast
cancer: what would surgeons choose for themselves?" Eff Clin Pract 2(4): 149-51.
Dacey, Lawrence J. and David W. Johnstone (2005). "Reducing the Risk of Lung
Cancer." JAMA: Journal of the American Medical Association 294(12): 1550-1551.
Finlayson, S. R. (2006). "The volume-outcome debate revisited." Am.Surg. 72(11):
1038-1042.
Katz, Steven J. and Sarah T. Hawley (2007). "From Policy To Patients And Back:
Surgical Treatment Decision Making For Patients With Breast Cancer." Health Affairs
26(3): 761-769.
KATZ, STEVEN J., PAULA M. LANTZ and JUDITH K. ZEMENCUK (2001). "Correlates
of Surgical Treatment Type for Women with Noninvasive and Invasive Breast Cancer."
JOURNAL OF WOMEN’S HEALTH & GENDER-BASED MEDICINE 10(7): 659-670.
Kauff, Noah D. and Kenneth Offit (2007). Modeling Genetic Risk of Breast Cancer.
JAMA: Journal of the American Medical Association: 2637-2639.
McBride, Deborah (2007). "Second Opinion May Change Breast Cancer Treatment."
ONS Connect 22(3): 7-7.
Naspinsky, S. and A. Siegel (2005). "Chondroblastoma metastasis to lung visualized on
bone scan." Clin.Nucl.Med. 30(2): 110-111.
Emerging Issues 54
Passage, K. J. and N. J. McCarthy (2007). "Critical review of the management of earlystage breast cancer in elderly women." Intern Med J 37(3): 181-9.
Rainsbury, R. M. (2003). "Training and skills for breast surgeons in the new millennium."
ANZ J Surg 73(7): 511-6.
Rainsbury, R. M. (2006). "Skin-sparing mastectomy." Br J Surg 93(3): 276-81.
Stanciu C, Trifan A, Khder SA. (2007). "Accuracy of colonoscopy in localizing colonic
cancer."
Stelzer, Keith J. (2004). "Breast surgery in the ‘Arimidex, Tamoxifen alone or in
combination’ (ATAC) trial: American women are more likely than women from the
United Kingdom to undergo mastectomy." Women’s Oncol Rev 2004 4: 305-306.
Tanner, Lindsey. (2007). "Study: Chemotherapy plus surgery helps colon cancer that
has spread to liver." Fosters Online Retrieved Sunday-June-12, from
http://www.fosters.com/apps/pbcs.dll/article?AID=/20070610/FOSTERS01/106050327/1/SPNEWS02.
Wells, W. A., P. A. Carney, M. S. Eliassen, A. N. Tosteson and E. R. Greenberg (1998).
"Statewide study of diagnostic agreement in breast pathology." J Natl Cancer Inst 90(2):
142-5.
Yao, M., J. B. Epstein, B. J. Modi, K. B. Pytynia, A. J. Mundt and L. E. Feldman (2007).
"Current surgical treatment of squamous cell carcinoma of the head and neck." Oral
Oncol 43(3): 213-23.
Zakaria, S. and A. C. Degnim (2007). "Prophylactic mastectomy." Surg Clin North Am
87(2): 317-31, viii.
Emerging Issues 55
Alternative Therapies
"Integrative oncology: complementary therapy for cancer survivors." (2007). J Support
Oncol 5(2): 74-5.
Cheetham, P. J., K. J. Le Monnier and S. F. Brewster (2001). "Attitudes and use of
alternative therapies in UK prostate cancer patients-isn't it time we were in the know?"
Prostate Cancer Prostatic Dis 4(4): 235-241.
DiGianni, Lisa M., Judy E. Garber and Eric P. Winer (2002). "Complementary and
Alternative Medicine Use Among Women With Breast Cancer." J Clin Oncol
20(suppl_1): 34s-38.
Dragnev, K. H., J. R. Rigas and E. Dmitrovsky (2000). "The retinoids and cancer
prevention mechanisms." Oncologist 5(5): 361-8.
Hyodo, I., N. Amano, K. Eguchi, M. Narabayashi, J. Imanishi, M. Hirai, T. Nakano and
S. Takashima (2005). "Nationwide survey on complementary and alternative medicine
in cancer patients in Japan." J Clin Oncol 23(12): 2645-54.
Michaud, L. B., J. P. Karpinski, K. L. Jones and J. Espirito (2007). "Dietary supplements
in patients with cancer: risks and key concepts, part 1." Am J Health Syst Pharm 64(4):
369-81.
Michaud, L. B., J. P. Karpinski, K. L. Jones and J. Espirito (2007). "Dietary supplements
in patients with cancer: risks and key concepts, part 2." Am J Health Syst Pharm 64(5):
467-80.
Navo, Marisa A., Julie Phan, Christy Vaughan, J. Lynn Palmer, Laura Michaud, Kellie L.
Jones, Diane C. Bodurka, Karen Basen-Engquist, Gabriel N. Hortobagyi, John J.
Kavanagh and Judith A. Smith (2004). "An Assessment of the Utilization of
Complementary and Alternative Medication in Women With Gynecologic or Breast
Malignancies." J Clin Oncol 22(4): 671-677.
Treasure, Jonathan. (2005). "Food, Medicine, Poison & "Molecular Vitalism"."
Retrieved 6/25/2007, from http://www.herbological.com/cancerandherbalmed.html.
Winquist, E., T. Waldron, S. Berry, D. S. Ernst, S. Hotte and H. Lukka (2006). "Nonhormonal systemic therapy in men with hormone-refractory prostate cancer and
metastases: a systematic review from the Cancer Care Ontario Program in Evidencebased Care's Genitourinary Cancer Disease Site Group." BMC Cancer 6: 112.
Emerging Issues 56
Other Emerging Issues in Cancer Treatment
Anderson, K. C. (2007). "Targeted therapy of multiple myeloma based upon tumormicroenvironmental interactions." Exp Hematol 35(4 Suppl 1): 155-62.
Ayash, L. J., V. Ratanatharathorn, T. Braun, S. M. Silver, C. M. Reynolds and J. P.
Uberti (2007). "Unrelated donor bone marrow transplantation using a chemotherapyonly preparative regimen for adults with high-risk acute myelogenous leukemia." Am J
Hematol 82(1): 6-14.
Bioresearch online. (2007). "Fat Kills Cancer: Turning Stem Cells From Fat Tissue Into
Personalized, Cancer-Targeted Therapeutics." from
http://www.bioresearchonline.com/content/news/article.asp?docid=f7836148-dbd44580-85ca-c4922aeec83f&atc~c=771+s=773+r=001+l=a&VNETCOOKIE=NO.
Eapen, M., P. Rubinstein, M. J. Zhang, C. Stevens, J. Kurtzberg, A. Scaradavou, F. R.
Loberiza, R. E. Champlin, J. P. Klein, M. M. Horowitz and J. E. Wagner (2007).
"Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow
in children with acute leukaemia: a comparison study." Lancet 369(9577): 1947-54.
Houghton, J. (2007). "Bone-marrow-derived cells and cancer--an opportunity for
improved therapy." Nat Clin Pract Oncol 4(1): 2-3.
Hwang, W. Y., M. Samuel, D. Tan, L. P. Koh, W. Lim and Y. C. Linn (2007). "A metaanalysis of unrelated donor umbilical cord blood transplantation versus unrelated donor
bone marrow transplantation in adult and pediatric patients." Biol Blood Marrow
Transplant 13(4): 444-53.
Kasamon, Y. L. (2007). "Blood or marrow transplantation for mantle cell lymphoma."
Curr Opin Oncol 19(2): 128-35.
Maurer, L. H., T. Davis, S. Hammond, E. Smith, P. West and M. Doolittle (2001).
"Clinical trials in a rural population: professional education aspects." J Cancer Educ
16(2): 89-92.
Medical News Today. (2007). "Researchers identify genetic mutation that may alter
patient's responce to cancer therapies. ." from
http://www.medicalnewstoday.com/medicalnews.php?newsid=76253.
Meehan, K. R., E. M. Areman, S. G. Ericson, C. Matias, R. Seifeldin and K. Schulman
(2000). "Mobilization, collection, and processing of autologous peripheral blood stem
cells: development of a clinical process with associated costs." J Hematother Stem Cell
Res 9(5): 767-71
Emerging Issues 57
Meehan, K. R., T. Fitzmaurice, L. Root, E. Kimtis, L. Patchett and J. Hill (2006). "The
financial requirements and time commitments of caregivers for autologous stem cell
transplant recipients." J Support Oncol 4(4): 187-90.
Meehan, K. R., J. M. Hill, L. Patchett, S. M. Webber, J. Wu, P. Ely and Z. M.
Szczepiorkowski (2006). "Implementation of peripheral blood CD34 analyses to initiate
leukapheresis: marked reduction in resource utilization." Transfusion 46(4): 523-9.
Meehan, K. R., R. Slack, E. Gehan, H. B. Herscowitz, E. M. Areman, M. Ebadi, M. S.
Cairo and M. E. Lippman (2002). "Mobilization of peripheral blood stem cells with
paclitaxel and rhG-CSF in high-risk breast cancer patients." J Hematother Stem Cell
Res 11(2): 415-21.
Meehan, K. R., J. Wu, E. Bengtson, J. Hill, P. Ely, Z. Szczepiorkowski, M. Kendall and
M. S. Ernstoff (2007). "Early recovery of aggressive cytotoxic cells and improved
immune resurgence with post-transplant immunotherapy for multiple myeloma." Bone
Marrow Transplant 39(11): 695-703.
Mittal, P, E Corteguerra and KR. Meehan (2001). "Post-transplantation immunotherapy
may improve long-term survival in high risk-breast cancer patients." Proc American
Society of Clinical Oncology 20: 14a.
News-Mecical.net. (2007). "Are we looking at cancer vaccines the wrong way?" from
http://www.news-medical.net/?id=27162.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer Treatment: Targeted Treatments. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Research and Treatment for Metastatic Disease. Nancy Ryan. Lee, NH,
New Hampshire Breast Cancer Coalition.
Suh, N., W. W. Lamph, A. L. Glasebrook, T. A. Grese, A. D. Palkowitz, C. R. Williams,
R. Risingsong, M. R. Farris, R. A. Heyman and M. B. Sporn (2002). "Prevention and
treatment of experimental breast cancer with the combination of a new selective
estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268." Clin Cancer
Res 8(10): 3270-5.
Sundaram, S., A. Sea, S. Feldman, R. Strawbridge, P. J. Hoopes, E. Demidenko, L.
Binderup and D. A. Gewirtz (2003). "The combination of a potent vitamin D3 analog, EB
1089, with ionizing radiation reduces tumor growth and induces apoptosis of MCF-7
breast tumor xenografts in nude mice." Clin Cancer Res 9(6): 2350-6.
physorg. (2007). "Discovery about obesity drug helping scientists develop new cancer
treatments." from http://www.physorg.com/news103126045.html.
Emerging Issues 58
Vaishampayan, U. N., L. K. Heilbrun, A. F. Shields, J. Lawhorn-Crews, K. Baranowski,
D. Smith and L. E. Flaherty (2007). "Phase II trial of interferon and thalidomide in
metastatic renal cell carcinoma." Invest New Drugs 25(1): 69-75.
Wu, A., A. Mazumder, R. L. Martuza, X. Liu, M. Thein, K. R. Meehan and S. D. Rabkin
(2001). "Biological purging of breast cancer cells using an attenuated replicationcompetent herpes simplex virus in human hematopoietic stem cell transplantation."
Cancer Res 61(7): 3009-15.
Emerging Issues 59
SECTION D: PALLIATION
Emerging Issues 60
General
Anast, J. W., G. L. Andriole and R. L. Grubb, 2nd (2007). "Managing the local
complications of locally advanced prostate cancer." Curr Urol Rep 8(3): 211-6.
Byock, I., J. S. Twohig, et al. (2006). "Promoting excellence in end-of-life care: a report
on innovative models of palliative care." J Palliat Med 9(1): 137-51.
Cobb, J. l., M. J. Glantz, et al. (2000). "Delirium in Patients with Cancer at the End of
Life." Cancer Practice 8(4): 6.
Fellowes, D, K Barnes and S Wilkinson (2004). "Aromatherapy and massage for
symptom relief in patients with cancer." Cochrane Database Syst Rev. 2(CD002287).
Himelstein, B. P. (2006). "Palliative care for infants, children, adolescents, and their
families." J Palliat Med 9(1): 163-81.
Jocham, HR, T Dassen, G Widdershoven and R Halfens (2006 Sep). "Quality of life in
palliative care cancer patients: a literature review." J Clin Nurs 15(9): 1188-95.
McDonah, D. (2007). Interview with Dr. Don McDonah, Chair of the Palliative
Workgroup, by Jaime Ingalls.
Meier, D. E. (2005). "Ten Steps to Growing Palliative Care Referrals." Journal of
Palliative Medicine 8(4): 706-708.
Podnos, Y. D. and L. D. Wagman (2007). "The surgeon and palliative care." Ann Surg
Oncol 14(4): 1257-63.
Von Gunten, C. F. (2005). "Innovations in Palliative Care." Journal of Palliative Medicine
8(4): 694-695.
Introduces several articles, which focused on palliative care.
Workman, S. and O. E. Mann (2007). "'No control whatsoever': end-of-life care on a
medical teaching unit from the perspective of family members." QJM 100(7): 433-40.
Emerging Issues 61
Pharmaceutical Palliation
"Chemotherapy as palliation in advanced colon cancer." (2007). J Support Oncol 5(2):
66.
Ali, A. S. and F. C. Hamdy (2007). "The spectrum of prostate cancer care: from curative
intent to palliation." Curr Urol Rep 8(3): 245-52.
Braga, S., A. Miranda, R. Fonseca, J. L. Passos-Coelho, A. Fernandes, J. D. Costa and
A. Moreira (2007). "The aggressiveness of cancer care in the last three months of life: a
retrospective single centre analysis." Psychooncology.
Fleisch, M. C., P. Pantke, M. W. Beckmann, H. G. Schnuerch, R. Ackermann, M. O.
Grimm, H. G. Bender and P. Dall (2007). "Predictors for long-term survival after
interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers." J Surg
Oncol 95(6): 476-84.
Franchi, F., P. Grassi, D. Ferro, G. Pigliucci, M. De Chicchis, G. Castigliani, C. Pastore
and P. Seminara (2007). "Antiangiogenic metronomic chemotherapy and hyperthermia
in the palliation of advanced cancer." Eur J Cancer Care (Engl) 16(3): 258-62.
Hackbarth, M., N. Haas, C. Fotopoulou, W. Lichtenegger and J. Sehouli (2007).
"Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life
in women's cancers. Results of a prospective study." Support Care Cancer.
Haddad, A., M. Davis and R. Lagman (2007). "The pharmacological importance of
cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for
avoiding adverse drug interactions." Support Care Cancer 15(3): 251-7.
Jassem, J. (2007). "The role of radiotherapy in lung cancer: where is the evidence?"
Radiother Oncol 83(2): 203-13.
Lutz, S. T., E. L. Chow, W. F. Hartsell and A. A. Konski (2007). "A review of
hypofractionated palliative radiotherapy." Cancer 109(8): 1462-70.
McCloskey, S. A., M. L. Tao, C. M. Rose, A. Fink and A. M. Amadeo (2007). "National
survey of perspectives of palliative radiation therapy: role, barriers, and needs." Cancer
J 13(2): 130-7.
Rizk, S., A. Robert, A. Vandenhooft, M. Airoldi, G. Kornek and J. P. Machiels (2007).
"Activity of chemotherapy in the palliative treatment of salivary gland tumors: review of
the literature." Eur Arch Otorhinolaryngol 264(6): 587-94.
Emerging Issues 62
Scartozzi, M., E. Galizia, L. Verdecchia, R. Berardi, S. Antognoli, S. Chiorrini and S.
Cascinu (2007). "Chemotherapy for advanced gastric cancer: across the years for a
standard of care." Expert Opin Pharmacother 8(6): 797-808.
Simmonds, P. C. (2000). "Palliative chemotherapy for advanced colorectal cancer:
systematic review and meta-analysis. Colorectal Cancer Collaborative Group." Bmj
321(7260): 531-5.
Stinnett, S., L. Williams and D. H. Johnson (2007). "Role of chemotherapy for palliation
in the lung cancer patient." J Support Oncol 5(1): 19-24.
Tey, J., M. F. Back, T. P. Shakespeare, R. K. Mukherjee, J. J. Lu, K. M. Lee, L. C.
Wong, C. N. Leong and M. Zhu (2007). "The role of palliative radiation therapy in
symptomatic locally advanced gastric cancer." Int J Radiat Oncol Biol Phys 67(2): 3858.
Yi, S. K., M. Yoder, K. Zaner and A. E. Hirsch (2007). "Palliative radiation therapy of
symptomatic recurrent bladder cancer." Pain Physician 10(2): 285-90.
Emerging Issues 63
Emotional, Spiritual, and Social Palliation
"Cancer survivors: issues in symptom management." (2007). J Support Oncol 5(2): 73.
Astin, John A., Shauna L. Shapiro, David M. Eisenberg and Kelly L. Forys (2003).
"Mind-Body Medicine: State of the Science, Implications for Practice." J Am Board Fam
Pract 16(2): 131-147.
Avis, N. E., E. Ip and K. L. Foley (2006). "Evaluation of the Quality of Life in Adult
Cancer Survivors (QLACS) scale for long-term cancer survivors in a sample of breast
cancer survivors." Health Qual Life Outcomes 4: 92.
Byock, I. (2007). "To life! Reflections on spirituality, palliative practice, and politics." The
American Journal of Hospice and Palliative Care 23(6): 436-438.
Carey, L. (2005). "Bosom Buddies: a practical model of expressive disclosure." J
Cancer Educ 20(4): 251-5.
Fletcher, K. E., L. Clemow, B. A. Peterson, S. C. Lemon, B. Estabrook and J. G. Zapka
(2006). "A path analysis of factors associated with distress among first-degree female
relatives of women with breast cancer diagnosis." Health Psychol 25(3): 413-24.
Redd, William H., Guy H. Montgomery and Katherine N. DuHamel (2001). "Behavioral
Intervention for Cancer Treatment Side Effects." J. Natl. Cancer Inst. 93(11): 810-823.
Emerging Issues 64
Medical Marijuana
Medical marijuana is a key alternative (2007). USA Today: 10a.
Biskupic, Joan (2007). Medical pot rejected: Government can prosecute users, justices
decide. USA Today: 1A.
Gorter, R. W., M. Butorac, E. P. Cobian and W. van der Sluis (2005). "Medical use of
cannabis in the Netherlands." Neurology 64(5): 917-9.
Klein, T. W. (2005). "Cannabinoid-based drugs as anti-inflammatory therapeutics." Nat
Rev Immunol 5(5): 400-11.
Manderson, Desmond (1999, Winter). "FORMALISM AND NARRATIVE IN LAW AND
MEDICINE: THE DEBATE OVER MEDICAL MARIJUANA USE." Journal of Drug Issues
29(1): 121-133.
Scholten, W. K. (2005). "Medicinal cannabis in oncology practice: still a bridge too far?"
J Clin Oncol 23(30): 7755-6; author reply 7756.
Schwartz, Richard H. and Michael J. Sheridan (Feb1997). "Marijuana to prevent nausea
and vomiting in cancer patients: A survey of clinical oncologists." Southern Medical
Journal 90(2).
Seamon, Matthew J., Jennifer A. Fass, Maria Maniscalco-Feichtl and Nada A. AbuShraie (2007). "Medical marijuana and the developing role of the pharmacist." American
Journal of Health-System Pharmacy 64(10): 1037-1044.
Smigel, Kara (1997). "Cancer problems lead list for potential medical marijuana
research studies." Journal of the National Cancer Institute 89(17): 1255.
Twombly, Renee (2006). "Despite Research, FDA Says Marijuana Has No Benefit."
Journal of the National Cancer Institute 98(13): 888-889.
Emerging Issues 65
PART II: LITERATURE REVIEW WITH ABSTRACTS
Emerging Issues 66
SECTION A: PRIMARY PREVENTION
Emerging Issues 67
Behavior
Balluz, L., I. Ahluwalia, et al. (2004). "Surveillance for certain health behaviors among
selected local areas--United States, Behavioral Risk Factor Surveillance System, 2002."
MMWR Surveill Summ 53(5): 1-100.
PROBLEM: Monitoring risk behaviors for chronic diseases and participation in
preventive practices are important for developing effective health education and
intervention programs to prevent morbidity and mortality. Therefore, continual
monitoring of these behaviors and practices at the state, city, and county levels
can assist public health programs in evaluating and monitoring progress toward
improving their community's health. REPORTING PERIOD COVERED: Data
collected in 2002 are presented for states, selected metropolitan, and
micropolitan statistical areas (MMSA), and their counties. DESCRIPTION OF
THE SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an
on-going, state-based, telephone survey of the civilian, noninstitutionalized
population aged >18 years. All 50 states, the District of Columbia (DC), Guam,
the Virgin Islands, and the Commonwealth of Puerto Rico participated in BRFSS
during 2002. Metropolitan and MMSA and their counties with >500 respondents
or a minimum sample size of 19 per weighting class were included in the
analyses for a total of 98 MMSA and 146 counties. RESULTS: Prevalence of
high-risk behaviors for chronic diseases, awareness of certain medical
conditions, and use of preventive health-care services varied substantially by
state, county, and MMSA. Obesity ranged from 27.6% in West Virginia, 29.4% in
Charleston, West Virginia, and 32.0% in Florence County, South Carolina, to
16.5% in Colorado, 12.8% in Bethesda-Frederick-Gaithersburg, Maryland, and
11.8% in Washington County, Rhode Island. No leisuretime physical activity
ranged from 33.6% in Tennessee, 36.8% in Miami-Miami Beach-Kendall, Florida,
and 36.8% in Miami-Dade County, Florida to 15.0% in Washington, 13.8% in
Seattle-Bellevue-Everett Washington, and 11.4% in King County, Washington.
Cigarette smoking ranged from 32.6% in Kentucky, 32.8% in YoungstownWarren- Boardman, Ohio-Pennsylvania, and 31.1% in Jefferson County,
Kentucky to 16.4% in California, 13.8% in Ogden- Clearfield, Utah, and 10.9% in
Davis County, Utah. Binge drinking ranged from 24.9% in Wisconsin, 26.1% in
Fargo, North Dakota-Minnesota, and 25.1% Cass County, North Dakota, to 7.9%
in Kentucky, 8.2% in Greensboro- High Point, North Carolina, and 6.6% in
Henderson County, North Carolina. At risk for heavy drinking ranged from 8.7%
in Arizona, 9.5% in Lebanon, New Hampshire-Vermont, and 11.3% in Richland
County, South Carolina, to 2.8% in Utah, 1.9% in Ogden-Clearfield, Utah, and
1.7% in King County, New York. Adults who were told they had diabetes ranged
from 10.2% in West Virginia, 11.1% in Charleston, West Virginia, and 11.1% in
Richland, South Carolina, to 3.5% in Alaska, 2.7% in Anchorage, Alaska, and
2.4% in Weber County, Utah. Percentage of adults aged>50 years who were
ever screened for colorectal cancer ranged from 64.8% in Minnesota, 67.9% in
Minneapolis-St. Paul-Bloomington Minnesota-Wisconsin, and 73.6% in Ramsey
County, Minnesota, to 39.2% in Hawaii, 30.7% in Kahului-Wailuku, Hawaii, and
30.7% in Maui County, Hawaii. Persons aged >65 years who had received
Emerging Issues 68
pneumococcal vaccine ranged from 72.5% in North Dakota, 74.8% in
Minneapolis-St. Paul-Bloomington, Minnesota-Wisconsin, and 73.1% in
Milwaukee County, Wisconsin, to 47.9% in DC, 47.5% in New York-Wayne-White
Plains, New York, New Jersey, and 47.9% in DC County, DC. Older adults who
had received influenza vaccine ranged from 76.6% in Minnesota, 80.0% in
Minneapolis-St. Paul-Bloomington, Minnesota-Wisconsin, and 76.3% in
Middlesex County, Massachusetts, to 57.0% in Florida, 55.8% in HoustonBaytown-Sugar Land, Texas, and 56.2% in Cook County, Illinois.
INTERPRETATION: BRFSS data indicate substantial variation in high-risk
behaviors, participation in preventive healthcare services, and screening among
U.S. adults at states and selected local areas, indicating a need for continued
efforts to evaluate public health programs or policies designed to reduce
morbidity and mortality. PUBLIC HEALTH ACTIONS: Data from BRFSS are
useful in developing and guiding public health programs and policies. Therefore,
states, selected MMSA, and their counties can use BRFSS data as a tool to
prevent premature morbidity and mortality among adult population and to assess
progress toward national health objectives. The data indicate a continued need to
develop and implement health promotion programs for targeting specific
behaviors and practices and serve as a baseline for future surveillance at the
local level in the United States.
Emerging Issues 69
Tobacco Use
Boffetta, P. (2004). "Epidemiology of environmental and occupational cancer."
Oncogene 23(38): 6392-403.
Environmental carcinogens, in a strict sense, include outdoor and indoor air
pollutants, as well as soil and drinking water contaminants. An increased risk of
mesothelioma has consistently been detected among individuals experiencing
residential exposure to asbestos, while results for lung cancer are less
consistent. Several good-quality studies have investigated lung cancer risk from
outdoor air pollution based on measurement of specific agents. Their results tend
to show an increased risk in the categories at highest exposure, with relative
risks in the range 1.5. A causal association has been established between
exposure to environmental tobacco smoke and lung cancer, with a relative risk in
the order of 1.2. Radon is another carcinogen present in indoor air, with a relative
risk in the order of 1.06 for exposure at 100 Bq/m3. In several Asian populations,
an increased risk of lung cancer results among women from indoor pollution from
cooking and heating. There is strong evidence of an increased risk of bladder,
skin and lung cancers following consumption of water with high arsenic
contamination; results for other drinking water contaminants, including
chlorination by-products, are inconclusive. A total of 29 occupational agents are
established human carcinogens, and another 30 agents are suspected
carcinogens. In addition, at least 12 exposure circumstances entail exposure to
carcinogens. Exposure is still widespread for many important occupational
carcinogens, such as asbestos, coal tar, arsenic and silica, in particular in
developing countries. Although estimates of the global burden of occupational
and environmental cancer result in figures in the order of 2% and less than 1%,
respectively, these cancers concentrate in subgroups of the population;
furthermore, exposure is involuntary and can, to a large extent, be avoided.
Centers for Disease Control and Prevention, CDC (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
This report provides an ongoing assessment of the exposure to environmental
chemicals that people across the entire United States are exposed to. It includes
topics such as assessment of environmental chemical exposure through
biomonitoring, information collected by the National Center for Health Statistics of
the Centers for DIsease Control and Prevention from people surveyed across the
country, and the levels of twenty-seven environmental chemicals currently
measured in the U.S. population. The report is designed to provide information to
professionals in all areas of the public health community to fight diseases and
illnesses associated with exposure to environmental chemicals. Updates to the
report will be made in the subsequent reports that will follow in the years to
come.
Emerging Issues 70
Centers for Disease Control and Prevention, CDC (2003). Promising Practices in
Chronic Disease Prevention and Control: A Public Health Framework for Action, United
States Department of Health and Human Services: 195.
The Centers for Disease Control and Prevention (CDC) has developed this book
to share its vision of how states and their partners can reduce the prevalence of
chronic diseases and their risk factors by instituting comprehensive statewide
programs. The recommendations for achieving this vision are based on
prevention effectiveness research; program evaluations; and the expert opinions
of national, state, and local leaders and public health practitioners, including CDC
staff. In addition to describing some of the most promising practices available to
state programs, the book provides numerous sources, including Web sites, that
describe state and local examples of what can be achieved; state-of-the art
strategies, methods, and tools; and training opportunities. We hope that this book
will provide a framework that will help state and local health departments build
new chronic disease prevention and control programs and enhance existing
programs.
Centers for Disease Control and Prevention, CDC (2003). Second National Report on
Human Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services National Center for Environmental Health Division of Laboratory Sciences:
257.
This is the second report released by the Centers for Disease Control and
Prevention. It expands on the first report examining information from the two year
period of 1999 - 2000 and upgrading the number of environmental chemicals
from the orginal twenty-seven to one hundred sixteen. The report examines
biomonitoring results for the one hundred sixteen environmental chemical
compounds (present in air, water, soil, dust, or other environmental media) that
are present in all aspects of the American population. The goal of this report is
to aid the public health professional community to prevent diseases resulting
form exposure to these chemicals. Public health professionals can use the
information provided to help to determine which chemicals and what
concentrations reach the American public; determine the prevelance of chemical
toxicity levels present in humans; determine the reference ranges for ude during
high exposure diagnosis; assess the effectiveness of current public health
methods to reduce exposure; determine if higher exposure levels are present in
minorities, children, women of childbearing age, or other potentially vulnerable
groups; overtime track the levels of exposure trends in populations; and set
priorities on human health effects research. Information will be updated in future
reports to be released every two years.
Centers for Disease Control and Prevention, CDC (2005). Third National Report on
Human Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services Centers for Disease Control and Prevention National Center for Environmental
Health Division of Laboratory Sciences: 475.
Emerging Issues 71
This is the third report released by the Centers for Disease Control and
Prevention. It expands on the second report examining information obtained
during 2001 - 2002 and upgrading the number of environmental chemicals from
one hundred sixteen to one hundred forty-eight. The report examines
biomonitoring results for the one hundred forty-eight environmental chemical
compounds (present in air, water, soil, dust, or other environmental media) that
are present in all aspects of the American population. Information about
additional toxins from previously established chemical families has been
included. A random sample of blood and urine was collected from people
participating in the National Health and Nutrition Examination Survey (NHANES).
The goal of this report is to aid the public health professional community to
prevent diseases resulting form exposure to these chemicals. Public health
professionals can use the information provided to help to determine which
chemicals and what concentrations reach the American public; determine the
prevelance of chemical toxicity levels present in humans; determine the
reference ranges for ude during high exposure diagnosis; assess the
effectiveness of current public health methods to reduce exposure; determine if
higher exposure levels are present in minorities, children, women of childbearing
age, or other potentially vulnerable groups; overtime track the levels of exposure
trends in populations; and set priorities on human health effects research.
Reports are released every two years to hopefully make it possible to analyze
any trends that may be occurring.
Chapman, S. and J. Liberman (2005). "Ensuring smokers are adequately informed:
reflections on consumer rights, manufacturer responsibilities, and policy implications."
Tob Control 14 Suppl 2: ii8-13.
The right to information is a fundamental consumer value. Following the advent
of health warnings, the tobacco industry has repeatedly asserted that smokers
are fully informed of the risks they take, while evidence demonstrates widespread
superficial levels of awareness and understanding. There remains much that
tobacco companies could do to fulfil their responsibilities to inform smokers. We
explore issues involved in the meaning of "adequately informed" smoking and
discuss some of the key policy and regulatory implications. We use the idea of a
smoker licensing scheme-under which it would be illegal to sell to smokers who
had not demonstrated an adequate level of awareness-as a device to explore
some of these issues. We also explore some of the difficulties that addiction
poses for the notion that smokers might ever voluntarily assume the risks of
smoking.
Clapp, Richard W., Genevieve K. Howe and Molly M. Jacobs (2005). Environmental and
Occupational Causes of Cancer: A Review of Recent Scientific Literature, University of
Massachusetts Lowell: 50.
This report examines the links of exposure to environmental and occupational
elements to nearly thirty different types of cancer. The researchers include a
critique of the twenty-five year old Doll and Peto analysis, as well as highlights of
trends in cancer incidence and mortality rates. There are additional indications
Emerging Issues 72
that involuntary exposures are linked to cancers, as demonstrated by patterns in
geographic areas and in different populations including patterns seen in children.
The report associates cancer with multiple causes and no 100% cause.
Examples of strong causal links between environmental and occupational
exposures provided in the report include exposure to metals, chlorination
byproducts, natural fibers, petrochemicals and combustion products (PAHs),
pesticides, reactive chemicals, metal working fluids, ionizing radiation, solvents,
and environmental tobacco.
Dacey, Lawrence J. and David W. Johnstone (2005). "Reducing the Risk of Lung
Cancer." JAMA: Journal of the American Medical Association 294(12): 1550-1551.
Presents an editorial about reducing the risk of lung cancer. How cigarette
smoking causes about 5 million premature deaths each year; Assertion that it is
never too early or too late to stop smoking; Studies that appear in this issue
about smoking; Analysis of smoking cessation programs and what smokers can
do to decrease their risk of lung cancer.
Donovan, R. J., J. Jancey and S. Jones (2002). "Tobacco point of sale advertising
increases positive brand user imagery." Tob Control 11(3): 191-4.
OBJECTIVES: To determine the potential impact of point of sale advertising on
adolescents so as to inform changes to the Tobacco Control Act. DESIGN:
Participants were randomly assigned to one of two conditions. In the control
condition, students were exposed to a photograph of a packet of cigarettes; in
the intervention condition, students were exposed to an ad for cigarettes, typical
of point of sale advertising posters. All students then rated the brand user on a
set of 12 bipolar adjectives. Two brands were used in the study: Benson &
Hedges, and Marlboro. SUBJECTS: One hundred year (grade) 6 and 7 students
(age range 10-12 years), from four Western Australian metropolitan primary
schools, participated in the study. RESULTS: In a majority of the brand user
descriptions, the cigarette advertisements increased brand user imagery in a
positive way, especially for Benson & Hedges. For example, participants viewing
the Benson & Hedges advertisement, as distinct from those viewing the Benson
& Hedges pack only, were more likely to describe the Benson & Hedges user as
relaxed, interesting, cool, rich, adventurous, and classy. Relative to the Marlboro
pack only, the Marlboro ad increased positive perceptions of the Marlboro user
on adventurous, interesting, and relaxed. CONCLUSIONS: The results presented
here support restrictions being placed on advertising at point of sale, since such
ads have the potential to increase positive brand user imagery directly in the
situation where a product purchase can take place, and hence the potential to
increase the likelihood of impulse purchasing.
Hackbarth, D. P., D. Schnopp-Wyatt, D. Katz, J. Williams, B. Silvestri and M. Pfleger
(2001). "Collaborative research and action to control the geographic placement of
outdoor advertising of alcohol and tobacco products in Chicago." Public Health Rep
116(6): 558-67.
Emerging Issues 73
Community activists in Chicago believed their neighborhoods were being
targeted by alcohol and tobacco outdoor advertisers, despite the Outdoor
Advertising Association of America's voluntary code of principles, which claims to
restrict the placement of ads for age-restricted products and prevent billboard
saturation of urban neighborhoods. A research and action plan resulted from a
10-year collaborative partnership among Loyola University Chicago, the
American Lung Association of Metropolitan Chicago (ALAMC), and community
activists from a predominately African American church, St. Sabina Parish. In
1997 Loyola University and ALAMC researchers conducted a cross-sectional
prevalence survey of alcohol and tobacco outdoor advertising. Computer
mapping was used to locate all 4,247 licensed billboards in Chicago that were
within 500- and 1,000-foot radiuses of schools, parks, and playlots. A 50%
sample of billboards was visually surveyed and coded for advertising content.
The percentage of alcohol and tobacco billboards within the 500- and 1,000-foot
zones ranged from 0% to 54%. African American and Hispanic neighborhoods
were disproportionately targeted for outdoor advertising of alcohol and tobacco.
Data were used to convince the Chicago City Council to pass one of the nation's
toughest anti-alcohol and tobacco billboard ordinances, based on zoning rather
than advertising content. The ordinance was challenged in court by advertisers.
Recent Supreme Court rulings made enactment of local billboard ordinances
problematic. Nevertheless, the research, which resulted in specific legislative
action, demonstrated the importance of linkages among academic, practice, and
grassroots community groups in working together to diminish one of the social
causes of health disparities.
Henriksen, L. and S. P. Fortmann (2002). "Young adults' opinions of Philip Morris and
its television advertising." Tob Control 11(3): 236-40.
OBJECTIVE: To determine what young people think about the tobacco company
Philip Morris and how it affects their evaluations of the company's new television
advertising. DESIGN: Data were gathered in the context of a controlled
experiment in which participants saw four Philip Morris ads about youth smoking
prevention, four Philip Morris ads about charitable works, or four AnheuserBusch ads about preventing underage drinking (the control group). Knowledge
and opinion of Philip Morris were measured before ad exposure. SETTING: A
California state university in the San Francisco Bay area. SUBJECTS: A
convenience sample of undergraduates (n = 218) aged 18-25 years. MAIN
OUTCOME MEASURES: Advertising evaluation measured by 12 semantic
differential scales. RESULTS: A little more than half of the students knew that
Philip Morris is a tobacco company. Neither this knowledge nor students'
smoking status was related to their opinion of the company. Philip Morris ads
were rated less favourably by students who were aware that the sponsor is a
tobacco company than by students who were unaware. CONCLUSIONS:
Advertisements designed to discredit the tobacco industry typically avoid
references to specific companies. This study suggests that such counteradvertising would benefit from teaching audiences about the industry's corporate
identities.
Emerging Issues 74
Kelsey, K. T., T. Hirao, S. Hirao, T. Devi-Ashok, H. H. Nelson, A. Andrew, J. Colt, D.
Baris, J. S. Morris, A. Schned and M. Karagas (2005). "TP53 alterations and patterns of
carcinogen exposure in a U.S. population-based study of bladder cancer." Int J Cancer
117(3): 370-5.
The molecular pathology of bladder cancer has been the subject of considerable
interest, and current efforts are targeted toward elucidating the interrelationships
between individual somatic gene loss and both etiologic and prognostic factors.
Mutation of the TP53 gene has been associated with more invasive bladder
cancer, and evidence suggests that TP53 mutation, independent of stage, may
be predictive of outcome in this disease. However, there is no consensus in the
literature that bladder carcinogen exposure is associated with inactivation of the
TP53 gene. Work to date has been primarily hospital based and, as such, subject
to possible bias associated with selection of more advanced cases for study. We
examined exposure relationships with both TP53 gene mutation and TP53
protein alterations in a population-based study of 330 bladder cancer cases in
New Hampshire. Tobacco smoking was not associated with TP53 alterations. We
found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear
accumulation) among hair dye users (odd ratio [OR] = 4.1; 95% confidence
interval [CI] 1.2-14.7), and the majority of these mutations were transversions.
Men who had "at risk" occupations were more likely to have mutated TP53
tumors (OR = 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53
mutation (OR = 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR = 0.6;
95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure.
Our data suggest that there is exposure-specific heterogeneity in inactivation of
the TP53 pathway in bladder cancers and that integration of the spectrum of
pathway alterations in population-based approaches (capturing the full range of
exposures to bladder carcinogens) may provide important insights into bladder
tumorigenesis.
Kilfoy, B. A., K. S. Hudmon and J. R. Mande (2007). "Tobacco control in state
comprehensive cancer control plans: opportunities for decreasing tobacco-related
disease." Prev Chronic Dis 4(3): A61.
INTRODUCTION: Comprehensive cancer control plans published by state, tribal,
and territorial health agencies present an excellent opportunity to help prevent
tobacco-related and other cancers. In this analysis, we sought to estimate the
extent to which tobacco control activities outlined in state comprehensive cancer
control plans incorporated the tobacco control recommendations presented by
the Centers for Disease Control and Prevention (CDC) in Best Practices for
Comprehensive Tobacco Control Programs-August 1999 (Best Practices) and
The Guide to Community Preventive Services: Tobacco Use Prevention and
Control (The Guide). METHODS: We analyzed the 39 available state
comprehensive cancer control plans to determine which of the CDC tobacco
control recommendations were incorporated. We then summarized these data
across the 39 states. RESULTS: The 39 states incorporated a mean of 5.6
recommendations from Best Practices (SD, 2.8; range, 0-9) and 3.9
Emerging Issues 75
recommendations from The Guide (SD, 1.9; range, 0-6). Nearly one-half of state
plans (48.7%) addressed funding for tobacco control; of these, 52.6% (25.6% of
total) delineated a specific, measurable goal for funding. CONCLUSION: The
extent to which tobacco control is addressed in state comprehensive cancer
control plans varies widely. Our analysis revealed opportunities for states to
improve compliance with CDC's tobacco-related recommendations for cancer
control.
Kuper, H., L. Titus-Ernstoff, B. L. Harlow and D. W. Cramer (2000). "Population based
study of coffee, alcohol and tobacco use and risk of ovarian cancer." Int J Cancer 88(2):
313-8.
Coffee, alcohol and tobacco use have been examined in many epidemiologic
studies of ovarian cancer but findings have generally been inconclusive. To
explain prior inconsistent findings, we sought to determine whether associations
with these exposures might vary by histologic subtype of ovarian cancer or
menopausal status at diagnosis. We conducted a population-based case-control
study in eastern Massachusetts and New Hampshire involving 549 women with
newly-diagnosed epithelial ovarian cancer and 516 control women selected
either by random digit dialing or through lists of residents. Coffee and alcohol
consumption was assessed through a semi-quantitative food-frequency
questionnaire, and information on tobacco smoking was collected through
personal interview. Consumption of coffee and caffeine was associated with
increased risk for ovarian cancer but only among premenopausal women. There
was no increase in risk for ovarian cancer overall associated with tobacco or
alcohol use in either pre- or post-menopausal women. Association of borderline
significance for tobacco and invasive serous cancers and alcohol and mucinous
cancers were observed but reduced after adjustment for coffee consumption. We
conclude that coffee and caffeine consumption may increase risk for ovarian
cancer among premenopausal women and are findings that have some
epidemiologic and biologic support.
Marsit, C. J., M. R. Karagas, H. Danaee, M. Liu, A. Andrew, A. Schned, H. H. Nelson
and K. T. Kelsey (2006). "Carcinogen exposure and gene promoter hypermethylation in
bladder cancer." Carcinogenesis 27(1): 112-6.
Tobacco smoking, certain occupational exposures, and exposure to inorganic
arsenic in drinking water have been associated with the occurrence of bladder
cancer. However, in these tumors the exposure-associated pattern of somatic
alterations in genes in the causal pathway for disease has been poorly
characterized. In particular, the mechanism by which arsenic induces bladder
cancer and the effects of lower environmental levels of exposure remain
uncertain. Animal and in-vitro studies have suggested that arsenic and other
exposures may act through epigenetic mechanisms. We, therefore, examined, in
a population-based study of human bladder cancer, the relationship between
epigenetic silencing of three tumor suppressor genes, p16(INK4A), RASSF1A
and PRSS3, and exposure to both tobacco and arsenic in bladder cancer.
Promoter methylation of each of these genes occurred in approximately 30% of
Emerging Issues 76
bladder cancers, and both RASSF1A and PRSS3 promoter methylation were
associated with advanced tumor stage (P<0.001 and P<0.04, respectively).
Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A
(P<0.02) and PRSS3 (P<0.1) but not p16INK4A promoter methylation, in models
adjusted for stage and other factors. Cigarette smoking was associated with a
>2-fold increased risk of promoter methylation of the p16INK4A gene only, with
greater risk seen in patients with exposures more recent to disease diagnosis.
These results, from human bladder tumors, add to the body of animal and in vitro
evidence that suggests a role in epigenetic alterations for bladder carcinogens.
Moritsugu, K. P. (2007). "The 2006 Report of the Surgeon General: the health
consequences of involuntary exposure to tobacco smoke." Am J Prev Med 32(6): 542-3.
National Cancer Institute (2004). Cancer and the Environment: What You Need to
Know, What You Can Do, U.S. Department of Health and Human Services: 47.
The booklet provides an access for information regarding issues pertaing to
environmental exposure to toxic substances that have a connection to cancer.
Topics covered include the causes of cancer, the nature of cancer, known
environmental cancer-causing substances, laboratory testing, determining the
risk associated with cancer-causing substances, setting acceptable exposure
levels, changes in cancer trends over the past few years, and additional
information sources.
Silva, Idos S (2002). "Alcohol, tobacco and breast cancer: should alcohol be
condemned and tobacco acquitted?" British Journal of Cancer 87(12): 12.
Strahan, E. J., K. White, G. T. Fong, L. R. Fabrigar, M. P. Zanna and R. Cameron
(2002). "Enhancing the effectiveness of tobacco package warning labels: a social
psychological perspective." Tob Control 11(3): 183-90.
OBJECTIVE: To outline social psychological principles that could influence the
psychosocial and behavioural effects of tobacco warning labels, and to inform the
development of more effective tobacco warning labels. DATA SOURCES:
PsycInfo and Medline literature searches and expert guided selection of
principles and theories in social psychology and of tobacco warning labels,
including articles, books, and reports. CONCLUSIONS: Tobacco warning labels
represent a potentially effective method of influencing attitudes and behaviours.
This review describes social psychological principles that could be used to guide
the creation of more effective warning labels. The potential value of incorporating
warning labels into a broader public health education campaign is discussed, and
directions for future research are suggested.
U.S. Department of Health and Human Services, U.S.DHHS (2006). The Health
Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon
General. U.S. Department of Health and Human Services, Centers for Disease Control
and Prevention, Coordinating Center for Health Promotion, National Center for Chronic
Disease Prevention and Health Promotion, Office on Smoking and Health, U.S.
Emerging Issues 77
Department of Health and Human Services, Centers for Disease Control and
Prevention: 721.
Twenty-ninth report issued by the Surgeon General of the United States in
regards to the issue of exposure to secondhand smoke. Exposure to
secondhand smoke has been associated with lung cancer, heart disease nad
other non-fatal symptoms in otherwise healthy non-smokers. Since 1992, the
median continine (a metabolite of nicotine) levels throughout the population of
the United States have decreased. This decrease is attributed to the increase in
smoking restriction policies in public locations and workplace settings. Research
discussed in the report indicates that smoke-free policies are the most economic
and effective forms of providing protection to people in all sectors of the
population. The report also provides information regarding research pertaining to
the restriction of smoking in these areas having a reduction in the smoking habits
of active smokers.
Westmaas, J. L. and T. H. Brandon (2004). "Reducing risk in smokers." Curr Opin Pulm
Med 10(4): 284-8.
PURPOSE OF REVIEW: Tobacco smoking is a leading cause of lung cancer and
chronic obstructive pulmonary disease. For smokers who want to quit, nicotine
replacement therapy and bupropion are frequently recommended. Currently,
disagreement surrounds the extent of risk reduction from quitting, the
consequences of the change of nicotine replacement therapy to over-the-counter
status, and the safety and efficacy of new tobacco products being marketed by
tobacco companies. This article reviews the current evidence relevant to these
and other developments in smoking interventions and describes the most
effective strategies that smokers can use to reduce their risk. RECENT
FINDINGS: Although it may take approximately 10 to 30 years of abstinence for
former smokers' risk of lung cancer to reach that of never smokers, quitting at
any time is substantially less risky than continuing to smoke. Quitting after
diagnosis also prolongs survival. Bupropion and nicotine replacement therapy
are effective pharmacotherapies, doubling quit rates compared with self-quitting.
However, many users of over-the-counter nicotine replacement therapy are using
it inappropriately. More research is needed to determine the long-term health
effects of modified tobacco products and their efficacy in helping smokers quit.
Switching to "low tar" filter cigarettes to reduce lung cancer risk, however, is
clearly ineffective. The most effective interventions for quitting continue to be a
combination of behavioral and pharmacologic approaches. SUMMARY: Health
care practitioners should encourage all smokers to attempt cessation and
emphasize pharmacotherapy as an important aid to quitting. Professionals who
educate patients on the appropriate use of pharmacotherapy and follow-up on
smokers' attempts to quit will help reduce the societal burden and personal risks
of smoking.
Williams, A., E. Peterson, S. Knight, M. Hiller and A. Pelletier (2004). "Survey of
restaurants regarding smoking policies." J Public Health Manag Pract 10(1): 35-40.
Emerging Issues 78
The New Hampshire Indoor Smoking Act was implemented in 1994 to protect the
public's health by regulating smoking in enclosed places. A survey was
conducted of New Hampshire restaurants to determine smoking policies, to
determine restaurant characteristics associated with smoking policies, and to
evaluate compliance with the Indoor Smoking Act. A list of New Hampshire
restaurants was obtained from a marketing firm. Establishments were selected
randomly until 400 had completed a 22-question telephone survey. Forty-four
percent of restaurants permitted smoking. Characteristics positively associated
with permitting smoking were being a non-fast-food restaurant, selling alcohol,
selling tobacco, and having greater than the median number of seats. Of
restaurants permitting smoking, 96.1% had a designated smoking area, 87.0%
had a ventilation system to minimize secondhand smoke, 83.6% had a physical
barrier between smoking and nonsmoking areas, and 53.1% exhibited signs
marking the smoking area. Forty percent of restaurants permitting smoking met
all four requirements of the Indoor Smoking Act. Smoking policies differ, by type
of restaurant. Compliance with the Indoor Smoking Act is low.
Zakarian, J. M., M. F. Hovell, R. D. Sandweiss, C. R. Hofstetter, G. E. Matt, J. T.
Bernert, J. Pirkle and S. K. Hammond (2004). "Behavioral counseling for reducing
children's ETS exposure: implementation in community clinics." Nicotine Tob Res 6(6):
1061-74.
The present randomized controlled trial tested the effectiveness of a behavioral
counseling program for reducing children's exposure to environmental tobacco
smoke (ETS). Counseling was delivered by clinic staff as part of well-child health
care services in a community clinic setting. A total of 150 mothers with children
aged 4 years or younger were recruited. Parent-reported and children's urinary
cotinine measures of ETS exposure were obtained at baseline, 3 months, 6
months (post-test), and 12 months (follow-up). Saliva samples were obtained
from mothers who reported quitting smoking, for objective verification by
thiocyanate analysis. After baseline, mothers were randomly assigned to a
measures-only control condition or an intervention consisting of seven behavioral
counseling sessions over 6 months. Counseling included behavioral contracting,
self-monitoring, problem solving, and positive reinforcement. Results indicated
acceptable test-retest reliability and validity of measures. Parent-reported
measures indicated that, in both groups, children's exposure to their mothers'
tobacco smoke in the home and to all tobacco smoke declined steeply from
baseline to 6 months post-test, and remained essentially level during follow-up.
Mothers' smoking rates followed the same pattern. Children's urinary cotinine
concentrations did not show significant change over time in either group.
Findings on the fidelity of treatment implementation suggest that the structure
and funding of the community clinic health care system and associated staff
turnover and training issues resulted in participants receiving a less efficacious
intervention than in our past efficacy trials. Implications for future effectiveness
trials are discussed.
Emerging Issues 79
Zanieri, L., P. Galvan, L. Checchini, A. Cincinelli, L. Lepri, G. P. Donzelli and M. Del
Bubba (2007). "Polycyclic aromatic hydrocarbons (PAHs) in human milk from Italian
women: influence of cigarette smoking and residential area." Chemosphere 67(7): 126574.
The presence of PAH in breast milk collected from 32 smoking and non-smoking
lactating women, residing in urban and rural areas of Tuscany (Italy) was
investigated. The results indicated a significant contribution of tobacco smoke to
the PAH contamination of milk: the condensate contained in the cigarettes
smoked daily by each subject was strongly related with the polynuclear
hydrocarbon content (R(2)=0.92, P<0.005). An experiment carried out under
controlled exposure conditions to cigarette smoke allowed to demonstrate that
individual metabolic activity and smoking habits affect the PAH concentration in
milk samples. Mothers living in rural environments showed significantly lower
PAH concentrations than those observed in urban subjects. The risk evaluation
due to PAH ingestion via breast milk was assessed on the basis of the
acceptable daily intake of Benzo(a)pyrene in drinking water, evidencing that a
hazard cannot be excluded for heavy smokers residing in urban areas.
Emerging Issues 80
Exposure to Radiation
Ionizing Radiation
Albrecht M, Müller K, Köhn FM, Meineke V, Mayerhofer A. (2007). "Ionizing radiation
induces degranulation of human mast cells and release of tryptase." International
journal of radiation biology 83(8): 535-41.
Purpose: Skin fibrosis is a hallmark of ionizing radiation-induced tissue injury and
we hypothesized that mast cells via their products (especially tryptase) are
involved in this event. We therefore investigated whether: (i) irradiation with 5
Gray (Gy) is able to induce the release of the typical mast cell mediator tryptase
from human mast cells (HMC-1) in vitro, (ii) this effect can be influenced by
application of clinically relevant mast cell blockers, and (iii) irradiation leads to
mast cell degranulation in ex vivo skin culture models. Materials and methods:
The human mast cell line (HMC)-1, as well as ex vivo skin tissue served as
experimental models. Fluorescence activated cell sorting (FACS), Enzyme linked
immunosorbent assays (ELISA), mast cell degranulation assays and
immunohistochemistry were applied. Results: Ionizing radiation induces a timedependent, statistically significant increase in the release of tryptase by HMC-1
cultured in vitro. Mast cell degranulation and secretion of tryptase was partially,
but not significantly, inhibited by pre-incubation with the histamine-1 receptor
(H1) blocker cetirizine. Mast cell degranulation was also clearly evident after
irradiation using an ex vivo skin culture model of mastocytoma tissue.
Conclusions: We propose that ionizing radiation leads to a degranulation of
dermal mast cells, an event which is accompanied by the release of tryptase.
Belson, Martin, Beverely Kingsley and Adrianne Holmes (2007/1). "Risk Factors for
Acute Leukemia in Children: A Review." Environmental Health Perspectives 115(1):
138-145.
Although overall incidence is rare, leukemia is the most common type of
childhood cancer. It accounts for 30% of all cancers diagnosed in children
younger than 15 years. Within this population, acute lymphocytic leukemia (ALL)
occurs approximately five times more frequently than acute myelogenous
leukemia (AML) and accounts for approximately 78% of all childhood leukemia
diagnoses. Epidemiologic studies of acute leukemias in children have examined
possible risk factors, including genetic, infectious, and environmental, in an
attempt to determine etiology. Only one environmental risk factor (ionizing
radiation) has been significantly linked to ALL or AML. Most environmental risk
factors have been found to be weakly and inconsistently associated with either
form of acute childhood leukemia. Our review focuses on the demographics of
childhood leukemia and the risk factors that have been associated with the
development of childhood ALL or AML. The environmental risk factors discussed
include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides,
alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular
Emerging Issues 81
risk factors can be used to support measures to reduce potentially harmful
exposures and decrease the risk of disease. We also review genetic and
infectious risk factors and other variables, including maternal reproductive history
and birth characteristics.
Cardis, Elisabeth, Janet Hall and Sean V Tavtigian (2007). "Identification of women with
an increased risk of developing radiation-induced breast cancer." Breast Cancer
Research 9(106).
In the previous issue of Breast Cancer Research, Broeks and collaborators
present the results of a study suggesting that germline mutations in BRCA1,
BRCA2, ATM or CHEK2 may double the risk of radiation-induced contralateral
breast cancer following radiotherapy for a first breast cancer. The assocation
appeared to be strongest among women who were below the age of 40 at the
time of their first breast cancer and among women who developed their second
cancer 5 years or more after the first. While there were a number of
methodological issues that might limit the conclusions drawn from this paper, this
is one of several recent studies suggesting that carriers of pathogenic alleles in
DNA repair and damage recognition genes may have an increased risk of breast
cancer following exposure to ionising radiation, even at low doses. This finding
has important implications for the protection of breast cancer patients and their
close relatives. If confirmed, mutation carriers may wish to consider alternatives
to X-ray for diagnostic purposes. The need for tailored cancer treatment
strategies in carriers should also be evaluated carefully.
Chicago Tribune. (2007). "Overexposure to radiation is on the rise." from
http://www.chicagotribune.com/entertainment/chi0626_health_radiation_rjun26,1,3230065.story?track=rss.
Geggel, Laura. (2007). "Radiation from health scans causes concern: Increasing use
stirs cancer fears." from
http://seattlepi.nwsource.com/local/322432_radiation05.html?source=rss.
Lichter, Michael D., Margaret R. Karagas, Leila A. Mott, Steven K. Spencer, Therese A.
Stukel, E. Robert Greenberg and Group for the New Hampshire Skin Cancer Study
(2000). "Therapeutic Ionizing Radiation and the Incidence of Basal Cell Carcinoma and
Squamous Cell Carcinoma." Arch Dermatol 136(8): 1007-1011.
Objective To estimate the relative risk of developing basal cell carcinoma (BCC)
and squamous cell carcinoma (SCC) after receiving therapeutic ionizing
radiation. Design Population-based case-control study. Setting New Hampshire.
Patients A total of 592 cases of BCC and 289 cases of SCC identified through a
statewide surveillance system and 536 age- and sex-matched controls selected
from population lists. Main Outcome Measures Histologically confirmed BCC and
invasive SCC diagnosed between July 1, 1993, through June 30, 1995, among
New Hampshire residents. Results Information regarding radiotherapy and other
factors was obtained through personal interviews. An attempt was made to
review the radiation treatment records of subjects who reported a history of
Emerging Issues 82
radiotherapy. Overall, an increased risk of both BCC and SCC was found in
relation to therapeutic ionizing radiation. Elevated risks were confined to the site
of radiation exposure (BCC odds ratio, 3.30; 95% confidence interval, 1.60-6.81;
SCC odds ratio, 2.94; 95% confidence interval, 1.30-6.67) and were most
pronounced for those irradiated for acne exposure. For SCC, an association with
radiotherapy was observed only among those whose skin was likely to sunburn
with sun exposure. Conclusions These results largely agree with those of
previous studies on the risk of BCC in relation to ionizing radiation exposure. In
addition, they suggest that the risk of SCC may be increased by radiotherapy,
especially in individuals prone to sunburn with sun exposure.
Medical News Today. (2007). "Health Physics Society Annual Meeting To Address
Radiation Safety Issues - Including Improving Detection Of Breast Cancer." from
http://www.medicalnewstoday.com/medicalnews.php?newsid=75886.
World Health Organization. (2007). "What is Ionizing Radiation?" from
http://www.who.int/ionizing_radiation/about/what_is_ir/en/index.html.
Ultraviolet Radiation
Karagas, M. R., E. R. Greenberg, S. K. Spencer, T. A. Stukel and L. A. Mott (1999).
"Increase in incidence rates of basal cell and squamous cell skin cancer in New
Hampshire, USA. New Hampshire Skin Cancer Study Group." Int J Cancer 81(4): 5559.
We conducted a study to estimate the current incidence rates of basal-cell
carcinoma (BCC) and squamous-cell carcinoma (SCC) of the skin in the
population of New Hampshire (NH), USA, and to quantify recent changes in the
incidence rates of these malignancies. BCCs and SCCs diagnosed among NH
residents were identified through physician practices and central pathology
laboratories in NH and bordering regions from June 1979 through May 1980 and
from July 1993 through June 1994. For each diagnosis period, we estimated the
age-adjusted incidence rates for both BCC and SCC among both men and
women and for separate anatomic sites. Between 1979-1980 and 1993-1994,
incidence rates of SCC increased by 235% in men and by 350% in women.
Incidence rates of BCC increased by more than 80% in both men and women.
While the absolute increase was greatest for tumors of the head and neck, the
relative change was most pronounced for tumors on the trunk in men and on the
lower limb in women. Thus, there has been a marked rise in the incidence rates
of BCC and SCC skin cancers in NH in recent years. The anatomic pattern of
increase in BCC and SCC incidence is consistent with an effect of greater
sunlight exposure. Studies of BCC and SCC occurrence are needed to identify
possible behavioral and environmental factors and to assess possible changes in
diagnostic practices that might account for the rise in incidence of these common
malignancies.
Emerging Issues 83
Karagas, Margaret R., Virginia A. Stannard, Leila A. Mott, Mary Jo Slattery, Steven K.
Spencer and Martin A. Weinstock (2002). "Use of Tanning Devices and Risk of Basal
Cell and Squamous Cell Skin Cancers." J. Natl. Cancer Inst. 94(3): 224-226.
Use of artificial tanning devices that emit UV radiation, such as tanning lamps
and tanning beds, has become increasingly popular in the United States.
Although an excess risk of nonmelanoma skin cancers might be predicted from
this exposure, little epidemiologic data exist. We conducted a population-based,
case-control study that included 603 basal cell carcinoma (BCC) case patients,
293 squamous cell carcinoma (SCC) case patients, and 540 control subjects.
Study participants were interviewed in person to obtain information on tanning
device use, sun exposure history, sun sensitivity, and other risk factors for skin
cancer. Overall, any use of tanning devices was associated with odds ratios of
2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to
2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure
did not affect our results. Our findings suggest that the use of tanning devices
may contribute to the incidence of nonmelanoma skin cancers. They highlight the
need to further evaluate the potential risks of BCC and SCC that are associated
with tanning lamp exposure and the appropriate public health response.
Karagas, M. R., M. S. Zens, H. H. Nelson, K. Mabuchi, A. E. Perry, T. A. Stukel, L. A.
Mott, A. S. Andrew, K. M. Applebaum and M. Linet (2007). "Measures of cumulative
exposure from a standardized sun exposure history questionnaire: a comparison with
histologic assessment of solar skin damage." Am J Epidemiol 165(6): 719-26.
Ultraviolet radiation exposure is the dominant environmental determinant of all
major forms of skin cancer; however, the nature of the association is
incompletely understood. Existing instruments to capture sun exposure history
tend to yield reproducible results, but the validity of these responses is unknown.
To address this question, the authors examined the relation between responses
to a standardized sun exposure instrument and histologic evidence of actinic
damage in a population-based study of keratinocyte cancers from New
Hampshire diagnosed from July 1, 1997, through March 31, 2000. A single study
dermatopathologist histologically reviewed the adjacent skin of 925 skin cancer
biopsies for the presence of solar keratoses and the extent of solar elastosis. The
authors compared these measures with responses to a personal interview on
history of sunburns, sunbathing, and time spent outdoors. Focusing on sitespecific exposure, they found variables that estimated cumulative exposure
related to histologic evidence of actinic damage. In contrast, measures of
acute/intermittent exposure were generally unrelated to solar damage
histologically. Findings suggest that cumulative, but not intermittent, measures of
sun exposure derived from a personal interview appear to reflect a person's
exposure history based on histologic evidence.
Kricker, Anne and Bruce Armstrong (2006). "Does sunlight have a beneficial influence
on certain cancers?" Progress in Biophysics & Molecular Biology 92(1): 132-139.
Emerging Issues 84
Apperly [1941. The relation of solar radiation to cancer mortality in North
America. Cancer Research 1, 191-195] first proposed that increased mortality
from cancer in the north than in the south of the USA might be due to the south
to north decrease in ambient solar radiation. This inverse association between
ambient solar radiation and cancer mortality has been subsequently reported for
cancers of the colon, breast, ovary and prostate.While the evidence that sunlight
might be related to lower incidence or more favourable outcomes from cancer
came initially from ecological studies, case-control and cohort studies have now
shown a similar association of sun exposure with risks of colon, breast and
prostate cancers in individuals, and other studies in individuals have found that
serum and dietary vitamin D levels are associated with reduced risks of
colorectal cancer and, less certainly, prostate cancer.Studies in individuals have
recently also suggested an effect of sun exposure to reduce risk of non-Hodgkin
lymphoma and to increase survival after a diagnosis of melanoma. Data on
variation in survival from cancer by season of diagnosis suggest that sun
exposure may also improve outcome from cancers of the breast, colon and
prostate and Hodgkin lymphoma. (c) 2006 Elsevier Ltd. All rights reserved.
Miller, K. L., M. R. Karagas, P. Kraft, D. J. Hunter, P. J. Catalano, S. H. Byler and H. H.
Nelson (2006). "XPA, haplotypes, and risk of basal and squamous cell carcinoma."
Carcinogenesis 27(8): 1670-5.
Nucleotide excision repair (NER) is instrumental in removing DNA lesions caused
by ultraviolet (UV) radiation, the dominant risk factor for keratinocyte carcinoma,
including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We
evaluated whether BCC or SCC risk was influenced by the A23G single
nucleotide polymorphism (SNP) in Xeroderma pigmentosum group A (XPA),
which codes for an essential protein in NER. We also investigated whether
haplotypes of XPA, determined by seven haplotype-tagging SNPs, better define
susceptibility to keratinocyte carcinoma. Incident cases of BCC and SCC from
New Hampshire were identified through dermatologists and pathology
laboratories. Population-based controls were frequency-matched to cases by
gender and age. Cases of BCC (886) and of SCC (682) were compared with
controls (796). Models controlled for age, gender, pigmentation factors and
severe sunburns and were restricted to Caucasians. Using GG as the reference,
the A allele was less frequent among cases of BCC (OR(AG) = 0.82, 95% CI
(0.66, 1.01); OR(AA)= 0.74, 95% CI (0.53, 1.03); trend test P = 0.03) and SCC
(OR(AG) = 0.85, 95% CI (0.67, 1.07); OR(AA) = 0.74, 95% CI (0.52, 1.05); trend
test P = 0.05) than controls. Risk from > or =3 severe sunburns was elevated for
those with the GG genotype only, and this interaction was nearly significant for
BCC (P = 0.07). XPA genotype also modified a relationship between SCC and
the amount of pigmentation (P = 0.02). Using a haplotype analysis identifying
seven common XPA haplotypes indicated that the A23G polymorphism alone
captured the differences in susceptibility to keratinocyte carcinoma. The common
G allele of the A23G polymorphism was associated with an increased risk of
BCC and SCC and this polymorphism appeared to be the determining
polymorphism in XPA that alters cancer susceptibility.
Emerging Issues 85
Nelson, H. H., B. Christensen and M. R. Karagas (2005). "The XPC poly-AT
polymorphism in non-melanoma skin cancer." Cancer Lett 222(2): 205-9.
Signature UV-DNA lesions, cyclobutane dimers and 6-4 photoproducts, are
repaired via the nucleotide excision repair pathway. NER may be subdivided into
transcription-coupled repair and global genome repair, and the XPC protein is
specific to this latter repair pathway recognizing helix distorting lesions and
initiating their repair. Inactivating XPC mutations are associated with xeroderma
pigmentosa and an extremely high risk of skin cancer. A common polymorphism
in intron 9 of the XPC gene has been associated with both reduced repair of UVDNA damage (using the host-cell reactivation assay) and increased risk of
squamous cell head and neck cancer. Here, we have tested the hypothesis that
the XPC PAT+ polymorphism is associated with non-melanoma skin cancer
using a population-based case control study of skin cancer in New Hampshire
(n=1917). Overall, there was a modest decreased risk of squamous cell
carcinoma (SCC) among those with the homozygous variant PAT+/+ genotype
(OR 0.8, 95% CI 0.5-1.1) that was most evident among tanners (OR 0.4, 95% CI
0.1-1.1), however, these trends failed to reach statistical significance. There was
no association of the PAT+/+ genotype and basal cell carcinoma (OR 1.0, 95%
CO 0.7-1.3), however there was a modest, non-statistically significant, decreased
risk among those with the heterozygous genotype (OR 0.8, 95% CI 0.7-1.1). We
did not detect gene environment interactions for either SCC or BCC between the
XPC PAT genotype and average hours of UV exposure per week, painful
sunburn history, nor ionizing radiation therapy. These results suggest that the
XPC PAT+polymorphism does not play a major role in non-melanoma skin
cancer, but that it may slightly modify the risk of SCC among individuals with a
phenotype which results in low UV-DNA adduct burdens. These results require
further confirmation.
Nelson, H. H., K. T. Kelsey, L. A. Mott and M. R. Karagas (2002). "The XRCC1
Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of geneenvironment interaction." Cancer Res 62(1): 152-5.
XRCC1, a protein directly involved in the repair of DNA base damage, contains
at least three common polymorphisms. One of these, the codon 399 arg-->gln
variant, has been associated with several cancer-related biomarkers, suggesting
it may have functional significance in exposure-induced cancers. However,
results from case-control studies have yielded conflicting results. We investigated
the XRCC1 arg399gln polymorphism and its interaction with carcinogen
exposure in a large, population-based case-control study of non-melanoma skin
cancer. Cases were derived from an incident survey of all newly diagnosed nonmelanoma skin cancer in New Hampshire, and controls were population based
and frequency matched to cases on age and sex (n = 1176). Exposure
information was derived from a detailed interviewer-administered questionnaire,
and XRCC1 genotype was determined from blood-derived DNA using a PCRRFLP method. Overall, the XRCC1 homozygous variant gln399gln genotype was
related to a significantly reduced risk of both basal cell [BCC; odds ratio (OR) 0.7,
Emerging Issues 86
95% confidence interval 0.4-1.0] and squamous cell carcinoma (SCC; OR 0.6,
95% confidence interval 0.3-0.9). There was no significant gene-environment
interaction of the variant XRCC1 genotype and a history of therapeutic X-ray
exposure. However, there was a statistically significant multiplicative interaction
of XRCC1 genotype and lifetime number of sunburns in SCC [likelihood ratio test
(2 d.f.), P < 0.02]. Although the absolute risk of SCC associated with sunburns
was similar across genotypes, the relative risk of SCC associated with painful
sunburn history was significantly higher for homozygous variants than wild types
(OR 6.8 for gln399gln and 1.5 for arg399arg). In summary, our data show that
the homozygous XRCC1 variant (gln399gln) is associated with a lower risk of
non-melanoma skin cancer and suggest that the etiology of sunburn-related SCC
may be significantly different by XRCC1 genotype. These data, using the classic
skin carcinogenesis model, provide new insight on the role of the XRCC1 399
polymorphism in neoplasia and may help explain the conflicting results relating
this polymorphism to cancer risk at various sites.
Olson, A. L., C. Gaffney, P. Starr, J. J. Gibson, B. F. Cole and A. J. Dietrich (2007).
"SunSafe in the Middle School Years: a community-wide intervention to change earlyadolescent sun protection." Pediatrics 119(1): e247-56.
OBJECTIVE: Rising rates of skin cancer associated with early-life sun exposure
make it important to improve adolescent sun-protection practices. Our study
objective was to determine if a multicomponent community-wide intervention
could alter the decline in sun protection that begins in early adolescence.
METHODS: A randomized, controlled trial was conducted in 10 communities to
assess the impact of the SunSafe in the Middle School Years program. The
intervention sought to (1) educate and activate adults and peers to role model
and actively promote sun-protection practices and (2) create a pro-sun protection
community environment. It targeted school personnel, athletic coaches,
lifeguards, and clinicians and enlisted teens as peer advocates. Annual
observations of cross-sectional samples of teens at community beach/pool sites
were used to assess the impact of 1 and 2 years of intervention exposure
compared to grade-matched controls. The outcome was percent of body surface
protected by sunscreen, clothing, or shade. RESULTS: Observers determined
the sun protection level of 1927 adolescents entering 6th to 8th grades. After 2
years of intervention exposure, adolescents at the beach/pool in intervention
communities were significantly better protected than those in control
communities. Over 2 years, the percent of body surface area protected declined
by 23% in the control arm but only 8% in intervention arm. After intervention, the
average percent of body surface protected at intervention sites (66.1%) was
significantly greater than control sites (56.8%). Teens in intervention communities
reported sun-protection advice from more adult sources, were more likely to use
sunscreen, and applied it more thoroughly than control-site teens.
CONCLUSIONS: Our multicomponent model addressing adolescent sun
protection shows the power of engaging teens and adults from across the
community as role models and educators. This new ecological approach shows
Emerging Issues 87
promise in changing adolescent sun protection behaviors and reducing skin
cancer risks.
Press Release. (2007). "Survey reveals lack of awareness that US sunscreens provide
insufficient protection against skin cancer
", from http://www.prweb.com/releases/2007/7/prweb537619.htm.
Stryker, J. E., A. L. Yaroch, R. P. Moser, A. Atienza and K. Glanz (2007). "Prevalence of
sunless tanning product use and related behaviors among adults in the United States:
results from a national survey." J Am Acad Dermatol 56(3): 387-90.
Little is known about the use of sunless tanning products in the United States.
This report describes the prevalence and correlates of sunless tanning use,
comparing exclusive sunless tanners, exclusive indoor tanners, both sunless and
indoor tanners, and non-tanners with respect to sociodemographic and sun
protection behaviors.
Emerging Issues 88
Environmental Pollutants
General Exposure to Pollution
Angerer, J., U. Ewers, et al. (2007/5). "Human biomonitoring: State of the art."
International Journal of Hygiene & Environmental Health 210(3/4): 201-228.
Abstract: Human biomonitoring (HBM) of dose and biochemical effect nowadays
has tremendous utility providing an efficient and cost effective means of
measuring human exposure to chemical substances. HBM considers all routes of
uptake and all sources which are relevant making it an ideal instrument for risk
assessment and risk management. HBM can identify new chemical exposures,
trends and changes in exposure, establish distribution of exposure among the
general population, identify vulnerable groups and populations with higher
exposures and identify environmental risks at specific contaminated sites with
relatively low expenditure. The sensitivity of HBM methods moreover enables the
elucidation of human metabolism and toxic mechanisms of the pollutants. So,
HBM is a tool for scientists as well as for policy makers. Blood and urine are by
far the most approved matrices. HBM can be done for most chemical substances
which are in the focus of the worldwide discussion of environmental medicine.
This especially applies for metals, PAH, phthalates, dioxins, pesticides, as well
as for aromatic amines, perfluorinated chemicals, environmental tobacco smoke
and volatile organic compounds. Protein adducts, especially Hb-adducts, as
surrogates of DNA adducts measuring exposure as well as biochemical effect
very specifically and sensitively are a still better means to estimate cancer risk
than measuring genotoxic substances and their metabolites in human body
fluids. Using very sophisticated but nevertheless routinely applicable analytical
procedures Hb-adducts of alkylating agents, aromatic amines and nitro aromatic
compounds are determined routinely today. To extend the spectrum of
biochemical effect monitoring further methods should be elaborated which put up
with cleavage and separation of the adducted protein molecules as a measure of
sample preparation. This way all sites of adduction as well as further proteins,
like serum albumin could be used for HBM. DNA-adducts.
Aschengrau, A. (2006/6). "Drinking water detective story: connecting water
contamination and disease." Massachusetts Nurse 77(5): 9-9.
The article discusses the research of the Superfund Basic Research Program at
Boston University of Public Health on the connection of perchloroethylene (PCE)
and cancer in Cape Cod, Massachusetts. In 1980, the drinking water in the
region was contaminated with PCE and pesticides which brought high incidence
of cancer. In response, tests and hypotheses on the two subjects through the
Aschengrau was done and found that PCE solvent leached in drinking water
increased breast cancer riskThe article discusses the research of the Superfund
Basic Research Program at Boston University of Public Health on the connection
of perchloroethylene (PCE) and cancer in Cape Cod, Massachusetts. In 1980,
Emerging Issues 89
the drinking water in the region was contaminated with PCE and pesticides which
brought high incidence of cancer. In response, tests and hypotheses on the two
subjects through the Aschengrau was done and found that PCE solvent leached
in drinking water increased breast cancer risk
Boffetta, P. (2004). "Epidemiology of environmental and occupational cancer."
Oncogene 23(38): 6392-403.
Environmental carcinogens, in a strict sense, include outdoor and indoor air
pollutants, as well as soil and drinking water contaminants. An increased risk of
mesothelioma has consistently been detected among individuals experiencing
residential exposure to asbestos, while results for lung cancer are less
consistent. Several good-quality studies have investigated lung cancer risk from
outdoor air pollution based on measurement of specific agents. Their results tend
to show an increased risk in the categories at highest exposure, with relative
risks in the range 1.5. A causal association has been established between
exposure to environmental tobacco smoke and lung cancer, with a relative risk in
the order of 1.2. Radon is another carcinogen present in indoor air, with a relative
risk in the order of 1.06 for exposure at 100 Bq/m3. In several Asian populations,
an increased risk of lung cancer results among women from indoor pollution from
cooking and heating. There is strong evidence of an increased risk of bladder,
skin and lung cancers following consumption of water with high arsenic
contamination; results for other drinking water contaminants, including
chlorination by-products, are inconclusive. A total of 29 occupational agents are
established human carcinogens, and another 30 agents are suspected
carcinogens. In addition, at least 12 exposure circumstances entail exposure to
carcinogens. Exposure is still widespread for many important occupational
carcinogens, such as asbestos, coal tar, arsenic and silica, in particular in
developing countries. Although estimates of the global burden of occupational
and environmental cancer result in figures in the order of 2% and less than 1%,
respectively, these cancers concentrate in subgroups of the population;
furthermore, exposure is involuntary and can, to a large extent, be avoided.
Boffetta, P. (2006/9). "Human cancer from environmental pollutants: The
epidemiological evidence." Mutation Research/Genetic Toxicology & Environmental
Mutagenesis 608(2): 157-162.
Abstract: An increased risk of mesothelioma has been reported among
individuals experiencing residential exposure to asbestos, while results for lung
cancer are less consistent. Several studies have reported an increased risk of
lung cancer risk from outdoor air pollution: on the basis of the results of the
largest study, the proportion of lung cancers attributable to urban air pollution in
Europe can be as high as 10.7%. A causal association has been established
between second-hand tobacco smoking and lung cancer, which may be
responsible for 1.6% of lung cancers. Radon is another carcinogen present in
indoor air, which may be responsible for 4.5% of lung cancers. An increased risk
of bladder might be due to water chlorination by-products. The available
Emerging Issues 90
evidence on cancer risk following exposure to other environmental pollutants,
including, pesticides, dioxins and electro-magnetic fields, is inconclusive.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Environmental carcinogens, in a strict sense, include outdoor and indoor air
pollutants, as well as soil and drinking water contaminants. An increased risk of
mesothelioma has consistently been detected among individuals experiencing
residential exposure to asbestos, whereas results for lung cancer are less
consistent. At least 14 good-quality studies have investigated lung cancer risk
from outdoor air pollution based on measurement of specific agents. Their results
tend to show an increased risk in the categories at highest exposure, with relative
risks in the range 1.5-2.0, which is not attributable to confounders. Results for
other cancers are sparse. A causal association has been established between
exposure to environmental tobacco smoke and lung cancer, with a relative risk in
the order of 1.2. Radon is another carcinogen present in indoor air which may be
responsible for 1% of all lung cancers. In several Asian populations, an increased
risk of lung cancer is present in women from indoor pollution from cooking and
heating. There is strong evidence of an increased risk of bladder, skin and lung
cancers following consumption of water with high arsenic contamination; results
for other drinking water contaminants, including chlorination by-products, are
inconclusive. A precise quantification of the burden of human cancer attributable
to environmental exposure is problematic. However, despite the relatively small
relative risks of cancer following exposure to environmental carcinogens, the
number of cases that might be caused, assuming a causal relationship, is
relatively large, as a result of the high prevalence of exposure.
Buffler, P. A., M. L. Kwan, et al. (2005). "Environmental and Genetic Risk Factors for
Childhood Leukemia: Appraising the Evidence." Cancer Investigation 23(1): 60-75.
Childhood leukemia is the most common cause of malignancy under the age of
15, representing an annual incidence rate of 43 cases per million in the United
States. Confirmed clinical and epidemiologic associations explain less than 10%
of disease incidence, leaving 90% of cases with an unclear etiology. To
effectively study leukemia in children, one must recognize that this disease has a
multifactorial causal mechanism and a heterogeneous biological composition. In
addition, the timing of environmental exposures and genetic changes related to
disease risk must be considered. This review of both environmental and genetic
risk factors for childhood leukemia evaluates the current published literature and
synthesizes the available knowledge. Furthermore, attention is directed to
expected sources of new advances and the compelling current issues that need
to be addressed before further progress can be made. We discuss parental
occupational exposures, air pollution, other chemical exposures such as
household solvents and pesticides, radiation, dietary factors, immunological
factors, socioeconomic status, and genetic susceptibility. We hope to provide the
reader with an understanding of the challenge and promise that characterizes the
current and future directions in childhood leukemia research.
Emerging Issues 91
Centers for Disease Control and Prevention, C. (2001). National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human
Services: 72.
This report provides an ongoing assessment of the exposure to environmental
chemicals that people across the entire United States are exposed to. It includes
topics such as assessment of environmental chemical exposure through
biomonitoring, information collected by the National Center for Health Statistics of
the Centers for DIsease Control and Prevention from people surveyed across the
country, and the levels of twenty-seven environmental chemicals currently
measured in the U.S. population. The report is designed to provide information to
professionals in all areas of the public health community to fight diseases and
illnesses associated with exposure to environmental chemicals. Updates to the
report will be made in the subsequent reports that will follow in the years to
come.
Centers for Disease Control and Prevention. (2003). Second National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human Services
National Center for Environmental Health Division of Laboratory Sciences: 257.
This is the second report released by the Centers for Disease Control and
Prevention. It expands on the first report examining information from the two year
period of 1999 - 2000 and upgrading the number of environmental chemicals
from the orginal twenty-seven to one hundred sixteen. The report examines
biomonitoring results for the one hundred sixteen environmental chemical
compounds (present in air, water, soil, dust, or other environmental media) that
are present in all aspects of the American population. The goal of this report is
to aid the public health professional community to prevent diseases resulting
form exposure to these chemicals. Public health professionals can use the
information provided to help to determine which chemicals and what
concentrations reach the American public; determine the prevelance of chemical
toxicity levels present in humans; determine the reference ranges for ude during
high exposure diagnosis; assess the effectiveness of current public health
methods to reduce exposure; determine if higher exposure levels are present in
minorities, children, women of childbearing age, or other potentially vulnerable
groups; overtime track the levels of exposure trends in populations; and set
priorities on human health effects research. Information will be updated in future
reports to be released every two years.
Centers for Disease Control and Prevention. (2005). Third National Report on Human
Exposure to Environmental Chemicals, U.S. Department of Health and Human Services
Centers for Disease Control and Prevention National Center for Environmental Health
Division of Laboratory Sciences: 475.
This is the third report released by the Centers for Disease Control and
Prevention. It expands on the second report examining information obtained
during 2001 - 2002 and upgrading the number of environmental chemicals from
one hundred sixteen to one hundred forty-eight. The report examines
Emerging Issues 92
biomonitoring results for the one hundred forty-eight environmental chemical
compounds (present in air, water, soil, dust, or other environmental media) that
are present in all aspects of the American population. Information about
additional toxins from previously established chemical families has been
included. A random sample of blood and urine was collected from people
participating in the National Health and Nutrition Examination Survey (NHANES).
The goal of this report is to aid the public health professional community to
prevent diseases resulting form exposure to these chemicals. Public health
professionals can use the information provided to help to determine which
chemicals and what concentrations reach the American public; determine the
prevelance of chemical toxicity levels present in humans; determine the
reference ranges for ude during high exposure diagnosis; assess the
effectiveness of current public health methods to reduce exposure; determine if
higher exposure levels are present in minorities, children, women of childbearing
age, or other potentially vulnerable groups; overtime track the levels of exposure
trends in populations; and set priorities on human health effects research.
Reports are released every two years to hopefully make it possible to analyze
any trends that may be occurring.
Clapp, R. W., G. K. Howe, et al. (2005). Environmental and Occupational Causes of
Cancer: A Review of Recent Scientific Literature, University of Massachusetts Lowell:
50.
This report examines the links of exposure to environmental and occupational
elements to nearly thirty different types of cancer. The researchers include a
critique of the twenty-five year old Doll and Peto analysis, as well as highlights of
trends in cancer incidence and mortality rates. There are additional indications
that involuntary exposures are linked to cancers, as demonstrated by patterns in
geographic areas and in different populations including patterns seen in children.
The report associates cancer with multiple causes and no 100% cause.
Examples of strong causal links between environmental and occupational
exposures provided in the report include exposure to metals, chlorination
byproducts, natural fibers, petrochemicals and combustion products (PAHs),
pesticides, reactive chemicals, metal working fluids, ionizing radiation, solvents,
and environmental tobacco.
Greenberg, M. R. (2007). Contemporary Environmental and Occupational Health
Issues: More Breadth and Depth. American Journal of Public Health: 395-397.
This article focuses on environmental concerns in light of the 37th anniversary of
the first Earth Day. Issues mentioned include the lead standard for the protection
of the health of children, epidemiologic surveillance, obesity, sunlight and skin
cancer and global environmental risks as well as the pollution issues of the first
Earth Day in 1970.
Koehler, D. A., D. H. Bennett, et al. (2005). "Rethinking Environmental Performance
from a Public Health Perspective: A Comparative Industry Analysis." Journal of
Industrial Ecology 9(3): 143-167.
Emerging Issues 93
To date the most common measures of environmental performance used to
compare industries, and by extension firms or facilities, have been quantity of
pollution emitted or hazardous waste generated. Discharge information, however,
does not necessarily capture potential health effects. We propose an alternative
environmental performance measure that includes the public health risks of toxic
air emissions extended to industry supply chains using economic input-output
life-cycle assessment. Cancer risk to the U.S. population was determined by
applying a damage function to the Toxic Release Inventory (TRI) as modeled by
CalTOX, a multimedia multi-pathway fate and exposure model. Risks were then
translated into social costs using cancer willingness to pay. For a baseline
emissions year of 1998, 260 excess cancer cases were calculated for 116 TRI
chemicals, dominated by ingestion risk from polycyclic aromatic compounds and
dioxins emitted by the primary aluminum and cement industries, respectively.
The direct emissions of a small number of industry sectors account for most of
the U.S. population cancer risk. For the majority of industry sectors, however,
cancer risk per $1 million output is associated with supply chain upstream
emissions. Ranking industries by total (direct + upstream) supply chain risk per
economic output leads to different conclusions about the relative hazards
associated with these industries than a conventional ranking based on emissions
per economic output.
McNally, R. J. Q. and L. Parker (2006/4). "Environmental factors and childhood acute
leukemias and lymphomas." Leukemia & Lymphoma 47(4): 583-598.
This review considers recent studies regarding the role of environmental factors
in the etiology of childhood leukemia and lymphoma. Potential environmental risk
factors identified for childhood leukemia include exposure to magnetic fields of
more than 0.4 micro Tessla, exposure to pesticides, solvents, benzene and other
hydrocarbons, maternal alcohol consumption (but only for certain genotypes),
contaminated drinking water, infections, and high birth weight. The finding of
space-time clustering and seasonal variation also supports a role for infections.
There is little evidence linking childhood leukemia with lifetime exposure to
ionizing radiation although fetal exposures to X-rays are associated with
increased risk. Breast-feeding, consumption of fresh fruit and vegetables and
having allergies all appear to be protective. Burkitt lymphoma (BL) is confined to
areas of the world where malaria is endemic, with the additional involvement of
the Epstein-Barr virus (EBV) as a co-factor. Environmental risk factors suggested
for other types of non-Hodgkin lymphoma (NHL) include exposure to ionizing
radiation (both lifetime and antenatal), pesticides, and, in utero exposure to
cigarette smoke, benzene and nitrogen dioxide (via the mother). Hodgkin
lymphoma (HL) is especially associated with higher levels of socioeconomic
deprivation, but breast-feeding seems to confer lower risk. This is consistent with
an infection or immune-response mediated etiology for HL.
National Cancer Institute (2004). Cancer and the Environment: What You Need to
Know, What You Can Do, U.S. Department of Health and Human Services: 47.
Emerging Issues 94
The booklet provides an access for information regarding issues pertaing to
environmental exposure to toxic substances that have a connection to cancer.
Topics covered include the causes of cancer, the nature of cancer, known
environmental cancer-causing substances, laboratory testing, determining the
risk associated with cancer-causing substances, setting acceptable exposure
levels, changes in cancer trends over the past few years, and additional
information sources.
Neri, M., S. Bonassi, et al. (2006/1). "Children's exposure to environmental pollutants
and biomarkers of genetic damage: I. Overview and critical issues." Mutation
Research/Reviews in Mutation Research 612(1): 1-13.
Abstract: In the last decade, molecular epidemiological studies have provided
new perspectives on studying environmental risks in pediatric populations, based
on the growing understanding that children may be more susceptible to toxicants
than adults. Protecting children's health is a social priority, and specific research
programs have been initiated with this purpose in the United States and Europe.
These programs address the development of (i) less invasive methods for
biological specimens collection, (ii) specific tools for interpretation and validation
of biomarkers, (iii) methods for translating biomarker results into intervention
strategies and for integrating them with environmental monitoring and health
data, (iv) optimal ways to obtain consent and provide information to children
and/or their parents participating in the studies and (v) techniques for the
effective communication with policy makers and the public. Critical issues in
children's environmental research discussed in this paper include specific needs
of study design, exposure assessment, sample collection and ethics. Special
consideration is given to the autonomy of the child in giving consent, the details
and nature of the information provided, and the need to warrant controlled
access to sensitive information. The use of incentives such as gifts and payment
to ensure the participation of school-aged children is specifically discussed.
Examples of field studies that are focused on the effects of pesticides, air
pollution and formaldehyde are used to illustrate advantages and limitations of
biomarker studies in children.
Richardson, S. D. and T. A. Ternes (2005). "Water Analysis: Emerging Contaminants
and Current Issues." Anal. Chem. 77(12): 3807-3838.
This biennial review covers developments in water analysis during 2003-2004
and highlights new areas and discusses representative papers in the areas of
focus. A few significant references that appeared between January and February
2005 are also included. Other areas covered in this review include
pharmaceuticals, hormones, endocrine disrupting compounds, disinfection
byproducts, algal toxins, perchlorate, methyl tert-butyl ether, organotins, arsenic,
chiral contaminants, natural organic matter and microorganisms.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Role of the Environment. New Hampshire Breast Cancer Coalition. Lee,
NH.
Emerging Issues 95
Most researchers believe the environment plays a role in the development of
breast cancer but this issue is not well understood and is difficult to study. The
Silent Spring Institute and several other institutions recently conducted a
literature review of publications related to breast cancer and the environment
(http://www.sciencereview.silentspring.org/). The researchers created a public
database of their findings. This tool may serve as important step in reviewing
what we know and what we don't know about this issue. One of the National
Breast Cancer Coalition's top priorities is passage of The Breast Cancer and
Environmental Research Act (S.579/H.R.1157). The legislation would authorize
the National Institutes of Health to establish multi-institutional, multi-disciplinary
centers to study this critical issue. We need this national strategy to better
understand the role of the environment in breast cancer.
Tsai, J., W. E. Kaye, et al. (2006/1). "Wilms tumor and exposures to residential and
occupational hazardous chemicals." International Journal of Hygiene & Environmental
Health 209(1): 57-64.
Abstract: This case-control study examines the association between residential
tumor. The study included 303 cases recruited from six state cancer registries,
who were diagnosed between January 1, 1992 and December 31, 1995. A total
of 575 controls selected through random digit dialing were frequency matched to
the cases. A standard questionnaire was administered to participants during a
telephone interview. Parental residential addresses and locations of US
Environmental Protection Agency National Priority List (NPL) sites were
geocoded and analyzed, along with occupational exposure information. There
were no cases of Wilms tumor found in individuals living within one-half mile
distance of a hazardous waste site. However, elevated odds ratios were found
for using hairdressing chemicals, motor oil, paint, paint stripper, and pesticides
during the pregnancy term and during the 2-year period prior to birth. The
findings do not support the hypothesis that Wilms tumor is associated with
residing near an NPL site
Van Den Hazel, P., M. Zuurbier, et al. (2006). "Today's epidemics in children: Possible
relations to environmental pollution and suggested preventive measures." Acta
Paediatrica 95: 18-25.
Background: Facts and hypotheses on the relationship between some children's
diseases or disorders and external stressors during the developmental stage of a
child, both prenatally and postnatally are described in literature. In this paper the
following changes in patterns and causes of the main childhood illnesses are
summarized and recommendations for actions are made. • Prematurity • Intrauterine growth restriction • Testicular dysgenesis syndrome • Type I and Type II
diabetes • Asthma, atopy and hay fever • Autism • Attention deficit hyperactivity
disorder (ADHD) • Learning disabilities • Cancer • Obesity • Hearing problems
Results: Literature provides a growing amount of information on changing
patterns in childhood diseases. Conclusions: The following recommendations for
action are formulated: • Immediate research on endocrine disrupters in relation to
Emerging Issues 96
prematurity • Diabetes: avoid Maillard Compounds in liquid baby food and in food
in general: promote breastfeeding • Asthma: avoid exposure to smoking, the use
of chemical household products, dioxin and dioxin-like chemicals, and avoid air
pollution with high levels of particulate matter, especially around conception,
during pregnancy and in the first years of life • Autism: more research on
incidence and causes • ADHD and learning disabilities: more research on
prevalence and causes. Preventions: 1) preconception counselling to avoid
potentially harmful substances; 2) controlling and further lowering levels of
polychlorinated biphenyls, lead and methyl mercury • Cancer: promote
breastfeeding, carry out research into effects of foetal exposure to internal
fission-product radionuclides • Obesity: stop smoking in pregnancy, avoid
parental obesity, longer night sleep • Hearing problems: lower noise levels in
discotheques, promote the day-evening-night level to avoid noise.
Wigle, D. T., T. E. Arbuckle, et al. (2007/1). "Environmental Hazards: Evidence for
Effects on Child Health." Journal of Toxicology & Environmental Health: Part B 10(1): 339.
The human fetus, child, and adult may experience adverse health outcomes from
parental or childhood exposures to environmental toxicants. The fetus and infant
are especially vulnerable to toxicants that disrupt developmental processes
during relatively narrow time windows. This review summarizes knowledge of
associations between child health and development outcomes and environmental
exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs),
dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain
pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air
toxicants (especially particulate matter [PM] and ozone), chlorination disinfection
by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency
(RF) radiation, residential proximity to hazardous waste disposal sites, and
solvents. The adverse health effects linked to such exposures include fetal death,
birth defects, being small for gestational age (SGA), preterm birth, clinically overt
cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic
deficits, childhood cancer, asthma, other respiratory diseases, and acute
poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS,
and certain ambient air toxicants, produce adverse health effects at relatively low
exposure levels during fetal or child developmental time windows. For the many
associations supported by limited or inadequate epidemiologic evidence, major
sources of uncertainty include the limited number of studies conducted on
specific exposure-outcome relationships and methodologic limitations. The latter
include (1) crude exposure indices, (2) limited range of exposure levels, (3) small
sample sizes, and (4) limited knowledge and control of potential confounders.
Important knowledge gaps include the role of preconceptual paternal exposures,
a topic much less studied than maternal or childhood exposures. Large
longitudinal studies beginning before...
Arsenic
Emerging Issues 97
Andrew, A. S., J. L. Burgess, M. M. Meza, E. Demidenko, M. G. Waugh, J. W. Hamilton
and M. R. Karagas (2006). "Arsenic exposure is associated with decreased DNA repair
in vitro and in individuals exposed to drinking water arsenic." Environ Health Perspect
114(8): 1193-8.
The mechanism(s) by which arsenic exposure contributes to human cancer risk
is unknown ; however, several indirect cocarcinogenesis mechanisms have been
proposed. Many studies support the role of As in altering one or more DNA repair
processes. In the present study we used individual-level exposure data and
biologic samples to investigate the effects of As exposure on nucleotide excision
repair in two study populations, focusing on the excision repair crosscomplement 1 (ERCC1) component. We measured drinking water, urinary, or
toenail As levels and obtained cryopreserved lymphocytes of a subset of
individuals enrolled in epidemiologic studies in New Hampshire (USA) and
Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined
the effects of As on DNA repair in a cultured human cell model. Arsenic exposure
was associated with decreased expression of ERCC1 in isolated lymphocytes at
the mRNA and protein levels. In addition, lymphocytes from As-exposed
individuals showed higher levels of DNA damage, as measured by a comet
assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF)
challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA
expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell
culture. These data provide further evidence to support the ability of As to inhibit
the DNA repair machinery, which is likely to enhance the genotoxicity and
mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic
mechanism of action.
Andrew, A. S., M. R. Karagas and J. W. Hamilton (2003). "Decreased DNA repair gene
expression among individuals exposed to arsenic in United States drinking water." Int J
Cancer 104(3): 263-8.
Arsenic is well established as a human carcinogen, but its precise mechanism of
action remains unknown. Arsenic does not directly damage DNA, but may act as
a carcinogen through inhibition of DNA repair mechanisms, leading indirectly to
increased mutations from other DNA damaging agents. The molecular
mechanism underlying arsenic inhibition of nucleotide excision repair after UV
irradiation (Hartwig et al., Carcinogenesis 1997;18:399-405) is unknown, but
could be due to decreased expression of critical genes involved in nucleotide
excision repair of damaged DNA. This hypothesis was tested by analyzing
expression of repair genes and arsenic exposure in a subset of 16 individuals
enrolled in a population based case-control study investigating arsenic exposure
and cancer risk in New Hampshire. Toenail arsenic levels were inversely
correlated with expression of critical members of the nucleotide excision repair
complex, ERCC1 (r(2) = 0.82, p < 0.0001), XPF (r(2) = 0.56, p < 0.002), and XPB
(r(2) = 0.75, p < 0.0001). The internal dose marker, toenail arsenic level, was
more strongly associated with changes in expression of these genes than
drinking water arsenic concentration. Our findings, based on human exposure to
arsenic in a US population, show an association between biomarkers of arsenic
Emerging Issues 98
exposure and expression of DNA repair genes. Although our findings need
verification in a larger study group, they are consistent with the hypothesis that
inhibition of DNA repair capacity is a potential mechanism for the co-carcinogenic
activity of arsenic.
Ayotte, J. D., D. Baris, K. P. Cantor, J. Colt, G. R. Robinson, Jr., J. H. Lubin, M.
Karagas, R. N. Hoover, J. F. Fraumeni, Jr. and D. T. Silverman (2006). "Bladder cancer
mortality and private well use in New England: an ecological study." J Epidemiol
Community Health 60(2): 168-72.
STUDY OBJECTIVE: To investigate the possible relation between bladder
cancer mortality among white men and women and private water use in New
England, USA, where rates have been persistently raised and use of private
water supplies (wells) common. DESIGN: Ecological study relating age adjusted
cancer mortality rates for white men and women during 1985-1999 and
proportion of persons using private water supplies in 1970. After regressing
mortality rates on population density, Pearson correlation coefficients were
computed between residual rates and the proportion of the population using
private water supplies, using the state economic area as the unit of calculation.
Calculations were conducted within each of 10 US regions. SETTING: The 504
state economic areas of the contiguous United States. PARTICIPANTS: Mortality
analysis of 11 cancer sites, with the focus on bladder cancer. MAIN RESULTS:
After adjusting for the effect of population density, there was a statistically
significant positive correlation between residual bladder cancer mortality rates
and private water supply use among both men and women in New England
(men, r = 0.42; women, r = 0.48) and New York/New Jersey (men, r = 0.49;
women, r = 0.62). CONCLUSIONS: Use of well water from private sources, or a
close correlate, may be an explanatory variable for the excess bladder cancer
mortality in New England. Analytical studies are underway to clarify the relation
between suspected water contaminants, particularly arsenic, and raised bladder
cancer rates in northern New England.
Ayotte, J. D., B. T. Nolan, J. R. Nuckols, K. P. Cantor, G. R. Robinson, Jr., D. Baris, L.
Hayes, M. Karagas, W. Bress, D. T. Silverman and J. H. Lubin (2006). "Modeling the
probability of arsenic in groundwater in New England as a tool for exposure
assessment." Environ Sci Technol 40(11): 3578-85.
We developed a process-based model to predict the probability of arsenic
exceeding 5 microg/L in drinking water wells in New England bedrock aquifers.
The model is being used for exposure assessment in an epidemiologic study of
bladder cancer. One important study hypothesis that may explain increased
bladder cancer risk is elevated concentrations of inorganic arsenic in drinking
water. In eastern New England, 20-30% of private wells exceed the arsenic
drinking water standard of 10 micrograms per liter. Our predictive model
significantly improves the understanding of factors associated with arsenic
contamination in New England. Specific rock types, high arsenic concentrations
in stream sediments, geochemical factors related to areas of Pleistocene marine
inundation and proximity to intrusive granitic plutons, and hydrologic and
Emerging Issues 99
landscape variables relating to groundwater residence time increase the
probability of arsenic occurrence in groundwater. Previous studies suggest that
arsenic in bedrock groundwater may be partly from past arsenical pesticide use.
Variables representing historic agricultural inputs do not improve the model,
indicating that this source does not significantly contribute to current arsenic
concentrations. Due to the complexity of the fractured bedrock aquifers in the
region, well depth and related variables also are not significant predictors.
Bissen, Monique and Fritz H. Frimmel (2003). "Arsenic - a Review. Part I: Occurrence,
Toxicity, Speciation, Mobility." Acta hydrochimica et hydrobiologica 31(1): 9-18.
In natural waters arsenic concentrations up to a few milligrams per litre were
measured. The natural content of arsenic found in soils varies between 0.01
mg/kg and a few hundred milligrams per kilogram. Anthropogenic sources of
arsenic in the environment are the smelting of ores, the burning of coal, and the
use of arsenic compounds in many products and production processes in the
past. A lot of arsenic compounds are toxic and cause acute and chronic
poisoning. In aqueous environment the inorganic arsenic species arsenite
(As(III)) and arsenate (As(V)) are the most abundant species. The mobility of
these species is influenced by the pH value, the redox potential, and the
presence of adsorbents such as oxides and hydroxides of Fe(III), Al(III),
Mn(III/IV), humic substances, and clay minerals.
Bodwell, J. E., L. A. Kingsley and J. W. Hamilton (2004). "Arsenic at very low
concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GRmediated gene repression: complex dose-response effects are closely correlated with
levels of activated GR and require a functional GR DNA binding domain." Chem Res
Toxicol 17(8): 1064-76.
Arsenic (As) contamination of drinking water is considered a principal
environmental health threat throughout the world. Chronic intake is associated
with an increased risk of cancer, diabetes, and cardiovascular disease, and
recent studies suggest increased health risks at levels as low as 5-10 ppb. We
report here that 0.05-1 microM (6-120 ppb) As showed stimulatory effects on
glucocorticoid receptor (GR)-mediated gene activation in rat EDR3 hepatoma
cells of both the endogenous tyrosine aminotransferase (TAT) gene and the
reporter genes containing TAT glucocorticoid response elements. At slightly
higher concentrations (1-3 microM), the effects of As became inhibitory. Thus,
over this narrow concentration range, the effects of As changed from a 2- to 4fold stimulation to a greater than 2-fold suppression in activity. Interestingly, the
inhibitory effect of GR on both AP1- and NF-kappa B-mediated gene activation
was not affected by As. The magnitude of GR stimulation and inhibition by As
was highly dependent on the cellular level of hormone-activated GR. Mutational
deletion studies indicated that the central DNA binding domain (DBD) of GR is
the minimal region required for the As effect and does not require free
sulfhydryls. Point mutations located within the DBD that have known structural
consequences significantly altered the GR response to As. In particular, point
mutations in the DBD that confer a DNA-bound GR confirmation abolished the
Emerging Issues100
low dose As stimulatory effect but enhanced the inhibitory response, further
indicating that the DBD is important for mediating these As effects.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Environmental carcinogens, in a strict sense, include outdoor and indoor air
pollutants, as well as soil and drinking water contaminants. An increased risk of
mesothelioma has consistently been detected among individuals experiencing
residential exposure to asbestos, whereas results for lung cancer are less
consistent. At least 14 good-quality studies have investigated lung cancer risk
from outdoor air pollution based on measurement of specific agents. Their results
tend to show an increased risk in the categories at highest exposure, with relative
risks in the range 1.5-2.0, which is not attributable to confounders. Results for
other cancers are sparse. A causal association has been established between
exposure to environmental tobacco smoke and lung cancer, with a relative risk in
the order of 1.2. Radon is another carcinogen present in indoor air which may be
responsible for 1% of all lung cancers. In several Asian populations, an increased
risk of lung cancer is present in women from indoor pollution from cooking and
heating. There is strong evidence of an increased risk of bladder, skin and lung
cancers following consumption of water with high arsenic contamination; results
for other drinking water contaminants, including chlorination by-products, are
inconclusive. A precise quantification of the burden of human cancer attributable
to environmental exposure is problematic. However, despite the relatively small
relative risks of cancer following exposure to environmental carcinogens, the
number of cases that might be caused, assuming a causal relationship, is
relatively large, as a result of the high prevalence of exposure.
Colt, J. S., D. Baris, S. F. Clark, J. D. Ayotte, M. Ward, J. R. Nuckols, K. P. Cantor, D. T.
Silverman and M. Karagas (2002). "Sampling private wells at past homes to estimate
arsenic exposure: a methodologic study in New England." J Expo Anal Environ
Epidemiol 12(5): 329-34.
We are conducting a collaborative, population-based case-control study in
Maine, New Hampshire, and Vermont to investigate the reasons for the elevated
bladder cancer mortality in northern New England. Arsenic in drinking water is
one of the primary exposures under investigation. To estimate subjects' lifetime
exposure to waterborne arsenic, it will be necessary to obtain water samples
from private wells that subjects used in the past. We conducted a methodologic
study to assess the feasibility of locating and sampling from private wells at
subjects' past residences. Ninety-eight New Hampshire residents (mean age 67
years) completed a questionnaire requesting the complete address, dates of
occupancy, and drinking water sources for each home lived in since birth. An
interviewer then asked subjects for more detailed information about each home
to assist in a field search of past homes in the three-state study area of Maine,
New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they
had used a total of 103 private wells in 95 previous homes located in these three
states. We conducted a field search to locate these 95 homes, visited town
Emerging Issues101
offices to find the properties on tax maps and obtain the current owners' names
and addresses, attempted to obtain permission from the current owners to
sample the wells, and collected water samples. In all, 48 (47%) of the 103 past
wells in the study area were sampled successfully. The remaining wells were not
sampled because the homes were not located (22%) or had been demolished
(2%), permission to sample the wells was not obtained (17%), the wells had been
destroyed (7%) or could not be found on the grounds of the residence (3%), or
for other reasons (2%). Various approaches for improving the success rates for
sampling water from private wells are discussed, as is the use of predictive
modeling to impute exposures when sampling is not feasible.
Healthy New Hampshire. (2007). "Environmental Health: Arsenic." Retrieved June 2,
2007, from http://www.healthynh2010.org/arsenic.htm.
The mission of Healthy New Hampshire 2010 is to inspire action and focus
resources, engaging private and public partners, to improve the quality of life and years of healthy life - for the New Hampshire public.
Karagas, M. R., C. X. Le, S. Morris, J. Blum, X. Lu, V. Spate, M. Carey, V. Stannard, B.
Klaue and T. D. Tosteson (2001). "Markers of low level arsenic exposure for evaluating
human cancer risks in a US population." Int J Occup Med Environ Health 14(2): 171-5.
Epidemiologic studies conducted in the US have not previously detected an
association between regional drinking water arsenic concentrations and
corresponding cancer occurrence or mortality rates. To improve our estimation of
cancer risk and arsenic exposure in the USA, we have investigated the reliability
of several exposure markers. In the current study, we specifically evaluated the
long-term reproducibility of tap water and toenail concentrations of arsenic, and
the relation between water, toenail, and urinary measurement. Subjects included
99 controls in our case-control study on whom we requested a household tap
water sample and toenail clipping three to five years apart. Additionally,
participants were asked to provide a first morning void sample at the second
interview. Tap water arsenic concentrations ranged from undetectable (<0.01
microg/L) to 66.6 microg/L. We found a significant correlation between both
replicate water and toenail samples (intraclass correlation coefficient = 0.85, 95%
confidence interval = 0.79-0.89 for water, and intraclass correlation coefficient =
0.60, 95% confidence interval = 0.48-0.70 for toenails). The inter-method
correlations for water, urinary and toenail arsenic were all statistically significant
(r = 0.35, p = 0.0024 for urine vs water; r = 0.33, p = 0.0016 for toenail vs water
and r = 0.36, p = 0.0012 for urine vs toenails). Thus, we found both toenail and
water measurements of arsenic reproducible over a three- to five-year period.
Our data suggest that biologic markers may provide reliable estimates of internal
dose of low level arsenic exposure that can be used to assess cancer risk.
Karagas, M. R., J. S. Morris, J. E. Weiss, V. Spate, C. Baskett and E. R. Greenberg
(1996). "Toenail samples as an indicator of drinking water arsenic exposure." Cancer
Epidemiol Biomarkers Prev 5(10): 849-52.
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We conducted a pilot study to assess the utility of toenail arsenic concentrations
as an indicator of ingestion of arsenic-containing water. We enrolled 21
individuals whose household drinking water supply was provided by a private
well, including 10 individuals who lived in areas of New Hampshire where
elevated water levels of arsenic had been reported previously. Participants were
interviewed regarding use of their private (unregulated) wells for drinking and
cooking, and each provided a sample of water and toenail clippings. All
specimens were analyzed using instrumental neutron activation analysis with a
sensitivity of approximately 0.001 parts per million (ppm). Trace concentrations of
arsenic were detected in 15 of the 21 well water samples and in all toenail
clipping samples. Among the 10 individuals who lived in areas with reportedly
high arsenic levels in the water supply, the geometric mean toenail concentration
was 0.39 ppm (SE, 0.12 ppm); among the other 11 persons, the geometric mean
was 0.14 ppm (SE, 0.02 ppm; P = 0.005 for the difference between the two
means). The overall Spearman correlation between toenail and well water
arsenic was 0.67 (P = 0.009), and among those with detectable well water levels
of arsenic, the Spearman correlation was 0.83 (P = 0.0001). Based on the
regression analysis of those who had detectable water levels of arsenic, a 10-fold
increase in well water concentrations of arsenic was reflected by about a 2-fold
increase in toenail concentrations. These results indicate that concentrations of
arsenic in toenails reflect use of arsenic-containing drinking water.
Karagas, M. R., S. Park, H. H. Nelson, A. S. Andrew, L. Mott, A. Schned and K. T.
Kelsey (2005). "Methylenetetrahydrofolate reductase (MTHFR) variants and bladder
cancer: a population-based case-control study." Int J Hyg Environ Health 208(5): 321-7.
Functional variants in the methylenetetrahydrofolate reductase (MTHFR) gene,
including the 677C>T and 1298A>C polymorphisms, have been associated with
a moderately reduced risk of several cancers, including colorectal cancers. While
recent studies have investigated the role of these polymorphisms on bladder
cancer susceptibility, results have been mixed. To clarify the role of MTHFR
polymorphisms on bladder cancer risk, we genotyped MTHFR 677C > T and
MTHFR 1298A > C in a population-based study of bladder cancer of 352 patients
and 551 controls from New Hampshire, USA. The allelic frequency was 35.6%
for MTHFR 677C>T and 40.4% for MTHFR 1298A > C among controls. We
found no evidence of a main gene effect for either polymorphism (adjusted OR
for MTHFR 677C>T variants versus the reference genotype = 1.1; 95% CI, 0.81.4 and adjusted OR for MTHFR 1298A>C variants versus the reference
genotype = 1.0; 95% CI, 0.7-1.4). Odds ratios did not appear to differ by smoking
status or gender. We observed differences in the risk estimates for the MTHFR
polymorphisms by arsenic exposure, but they were not statistically significant (P
= 0.67 for MTHFR 677C > T and P = 0.12 for MTHFR 1298A>C). Thus, our
findings do not support the presence of a main gene effect. The possibility that
MTHFR polymorphism affects susceptibility to environmental exposures warrants
further consideration.
Emerging Issues103
Karagas, M. R., T. A. Stukel, J. S. Morris, T. D. Tosteson, J. E. Weiss, S. K. Spencer
and E. R. Greenberg (2001). "Skin cancer risk in relation to toenail arsenic
concentrations in a US population-based case-control study." Am J Epidemiol 153(6):
559-65.
Arsenic is a known carcinogen specifically linked to skin cancer occurrence in
regions with highly contaminated drinking water or in individuals who took
arsenic-containing medicines. Presently, it is unknown whether such effects
occur at environmental levels found in the United States. To address this
question, the authors used data collected on 587 basal cell and 284 squamous
cell skin cancer cases and 524 controls interviewed as part of a case-control
study conducted in New Hampshire between 1993 and 1996. Arsenic was
determined in toenail clippings using instrumental neutron activation analysis.
The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma
(BCC) were close to unity in all but the highest category. Among individuals with
toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios
were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI:
0.74, 2.81) for BCC, compared with those with concentrations at or below the
median. While the risks of SCC and BCC did not appear elevated at the toenail
arsenic concentrations detected in most study subjects, the authors cannot
exclude the possibility of a dose-related increase at the highest levels of
exposure experienced in the New Hampshire population.
Karagas, M. R., T. A. Stukel and T. D. Tosteson (2002). "Assessment of cancer risk and
environmental levels of arsenic in New Hampshire." Int J Hyg Environ Health 205(1-2):
85-94.
The Agency for Toxic Substances and Disease Registry (ATSDR) and the United
States (US) Environmental Protection Agency (EPA) Office of Solid Waste and
Emergency Response (OSWER) list arsenic as a major concern for Superfund
sites and the environment at large. Arsenic is clearly linked to skin, bladder, and
lung cancer occurrence in populations highly exposed to arsenic occupationally,
medicinally, or through contaminated drinking water (Agency for Toxic
Substances and Disease Registry, 1999; IARC, 1987). While these studies have
identified important adverse health effects, they cannot provide risk information at
lower levels of exposure such as those commonly found in the US. Additionally,
precise measurement of exposure is critical to assessing risk in populations
consuming relatively trace amounts of arsenic. In New Hampshire, domestic
wells serve roughly 40% of the population, and about 10% of these contain
arsenic concentrations in the controversial range of 10 to 50 micrograms/l. New
Hampshire, along with other states in New England, has among the highest
bladder cancer mortality rates in the country. Therefore, we are conducting a
population-based epidemiologic study in New Hampshire (1) to assess the risk of
skin and bladder cancer associated with arsenic exposure in a US population, (2)
to evaluate methods of quantifying individual exposure to arsenic at low to
moderate levels, and (3) to explore alternative models of determining the doseresponse relationship at the lower end of exposure. Our findings to date indicate
that toenail arsenic concentrations are a reliable, long-term biomarker of total
Emerging Issues104
arsenic exposure and reflect arsenic intake by drinking water containing 1
microgram/l or more. We found that urinary arsenic cannot be detected
consistently in a population for which drinking water arsenic is primarily below 50
micrograms/l. Lastly, our data suggest that use of a biologic marker along with
alternative statistical approaches may aid detection of the levels at which arsenic
may affect cancer occurrence in the US.
Karagas, M. R., T. D. Tosteson, J. Blum, B. Klaue, J. E. Weiss, V. Stannard, V. Spate
and J. S. Morris (2000). "Measurement of low levels of arsenic exposure: a comparison
of water and toenail concentrations." Am J Epidemiol 152(1): 84-90.
A study was conducted to evaluate toenail arsenic concentrations as a biologic
marker of drinking water arsenic exposure. Study subjects were controls in a US
population-based case-control study of nonmelanoma skin cancer, randomly
selected from drivers' license records (those < 65 years of age) and Medicare
enrollment files (those > or = 65 years of age). Between 1994 and 1997, a total of
540 controls were interviewed and toenail samples of sufficient weight were
collected from 506 (93.7%) of these. Beginning in 1995, a sample of tap water
was taken from the participants' homes; a total of 217 (98.6%) water samples
were obtained from the 220 subjects interviewed. Arsenic determinations were
made from toenail samples using neutron activation analysis. Water samples
were analyzed using hydride-generation magnet sector inductively coupled mass
spectrometry. Among 208 subjects with both toenail and water measurements,
the correlation (r) between water and nail arsenic was 0.65 (p < 0.001) among
those with water arsenic concentrations of 1 microg/liter or higher and 0.08 (p =
0.31) among those with concentrations below 1 microg/liter (overall r = 0.46, p <
0.001). Our data suggest that toenail samples provide a useful biologic marker
for quantifying low-level arsenic exposure.
Karagas, M. R., T. D. Tosteson, J. Blum, J. S. Morris, J. A. Baron and B. Klaue (1998).
"Design of an epidemiologic study of drinking water arsenic exposure and skin and
bladder cancer risk in a U.S. population." Environ Health Perspect 106 Suppl 4: 104750.
Ingestion of arsenic-contaminated drinking water is associated with an increased
risk of several cancers, including skin and bladder malignancies; but it is not yet
clear whether such adverse effects are present at levels to which the U.S.
population is exposed. In New Hampshire, detectable levels of arsenic have
been reported in drinking water supplies throughout the state. Therefore, we
have begun a population-based epidemiologic case-control study in which
residents of New Hampshire diagnosed with primary squamous cell (n = 900)
and basal cell (n = 1200) skin cancers are being selected from a special
statewide skin cancer incidence survey; patients diagnosed with primary bladder
cancers (n = 450) are being identified through the New Hampshire State Cancer
Registry. Exposure histories of these patients will be compared to a control group
of individuals randomly selected from population lists (n = 1200). Along with a
detailed personal interview, arsenic and other trace elements are being
measured in toenail clipping samples using instrumental neutron activation
Emerging Issues105
analysis. Household water samples are being tested on selected participants
using a hydride generation technique with high-resolution inductively coupled
plasma mass spectrometry. In the first 793 households tested arsenic
concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l.
Over 10% of the private wells contained levels above 10 microgram/l and 2.5%
were above 50 microgram/l. Based on our projected sample size, we expect at
least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer
or bladder cancer among individuals with the highest 5% toenail concentrations
of arsenic.
Karagas, M. R., T. D. Tosteson, J. S. Morris, E. Demidenko, L. A. Mott, J. Heaney and
A. Schned (2004). "Incidence of transitional cell carcinoma of the bladder and arsenic
exposure in New Hampshire." Cancer Causes Control 15(5): 465-72.
OBJECTIVE: Arsenic is a known bladder carcinogen and populations exposed to
high arsenic levels in their water supply have reported elevated bladder cancer
mortality and incidence rates. To examine the effects of lower levels of arsenic
exposure on bladder cancer incidence, we conducted a case-control study in
New Hampshire, USA where levels above 10 micro/l are commonly found in
private wells. METHODS: We studied 383 cases of transitional cell carcinoma of
the bladder cancer, newly diagnosed between July 1, 1994 and June 30, 1998
and 641 general population controls. Individual exposure to arsenic was
determined in toenail clippings using instrumental neutron activation analysis.
RESULTS: Among smokers, an elevated odds ratio (OR) for bladder cancer was
observed for the uppermost category of arsenic (OR: 2.17, 95% CI: 0.92-5.11 for
greater than 0.330 mcg/g compared to less than 0.06 micro/g). Among never
smokers, there was no association between arsenic and bladder cancer risk.
CONCLUSIONS: These, and other data, suggest that ingestion of low to
moderate arsenic levels may affect bladder cancer incidence, and that cigarette
smoking may act as a co-carcinogen.
Kelsey, K. T., T. Hirao, S. Hirao, T. Devi-Ashok, H. H. Nelson, A. Andrew, J. Colt, D.
Baris, J. S. Morris, A. Schned and M. Karagas (2005). "TP53 alterations and patterns of
carcinogen exposure in a U.S. population-based study of bladder cancer." Int J Cancer
117(3): 370-5.
The molecular pathology of bladder cancer has been the subject of considerable
interest, and current efforts are targeted toward elucidating the interrelationships
between individual somatic gene loss and both etiologic and prognostic factors.
Mutation of the TP53 gene has been associated with more invasive bladder
cancer, and evidence suggests that TP53 mutation, independent of stage, may
be predictive of outcome in this disease. However, there is no consensus in the
literature that bladder carcinogen exposure is associated with inactivation of the
TP53 gene. Work to date has been primarily hospital based and, as such, subject
to possible bias associated with selection of more advanced cases for study. We
examined exposure relationships with both TP53 gene mutation and TP53
protein alterations in a population-based study of 330 bladder cancer cases in
New Hampshire. Tobacco smoking was not associated with TP53 alterations. We
Emerging Issues106
found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear
accumulation) among hair dye users (odd ratio [OR] = 4.1; 95% confidence
interval [CI] 1.2-14.7), and the majority of these mutations were transversions.
Men who had "at risk" occupations were more likely to have mutated TP53
tumors (OR = 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53
mutation (OR = 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR = 0.6;
95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure.
Our data suggest that there is exposure-specific heterogeneity in inactivation of
the TP53 pathway in bladder cancers and that integration of the spectrum of
pathway alterations in population-based approaches (capturing the full range of
exposures to bladder carcinogens) may provide important insights into bladder
tumorigenesis.
Marsit, C. J., M. R. Karagas, H. Danaee, M. Liu, A. Andrew, A. Schned, H. H. Nelson
and K. T. Kelsey (2006). "Carcinogen exposure and gene promoter hypermethylation in
bladder cancer." Carcinogenesis 27(1): 112-6.
Tobacco smoking, certain occupational exposures, and exposure to inorganic
arsenic in drinking water have been associated with the occurrence of bladder
cancer. However, in these tumors the exposure-associated pattern of somatic
alterations in genes in the causal pathway for disease has been poorly
characterized. In particular, the mechanism by which arsenic induces bladder
cancer and the effects of lower environmental levels of exposure remain
uncertain. Animal and in-vitro studies have suggested that arsenic and other
exposures may act through epigenetic mechanisms. We, therefore, examined, in
a population-based study of human bladder cancer, the relationship between
epigenetic silencing of three tumor suppressor genes, p16(INK4A), RASSF1A
and PRSS3, and exposure to both tobacco and arsenic in bladder cancer.
Promoter methylation of each of these genes occurred in approximately 30% of
bladder cancers, and both RASSF1A and PRSS3 promoter methylation were
associated with advanced tumor stage (P<0.001 and P<0.04, respectively).
Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A
(P<0.02) and PRSS3 (P<0.1) but not p16INK4A promoter methylation, in models
adjusted for stage and other factors. Cigarette smoking was associated with a
>2-fold increased risk of promoter methylation of the p16INK4A gene only, with
greater risk seen in patients with exposures more recent to disease diagnosis.
These results, from human bladder tumors, add to the body of animal and in vitro
evidence that suggests a role in epigenetic alterations for bladder carcinogens.
New Hampshire Department of Environmental Services. (2006). "Arsenic in Drinking
Water." Retrieved May 27, 2007, from http://www.des.state.nh.us/factsheets/ws/ws-32.htm.
A NH Department of Environmental Services fact sheet on arsenic in drinking
water, health effects, water testing, and water treatment options.
Emerging Issues107
New Hampshire Department of Environmental Services. (2007). "Arsenic:
Comprehensive Health Information Summary." Retrieved May 27, 2007, from
http://www.des.state.nh.us/factsheets/ehp/ard-ehp-1a.htm.
New Hampshire Department of Environmental Services. (2007). "Arsenic: Health
Information Summary." Retrieved May 27, 2007, 2007, from
http://www.des.state.nh.us/factsheets/ehp/ard-ehp-1.htm.
Wickre, J. B., C. L. Folt, S. Sturup and M. R. Karagas (2004). "Environmental exposure
and fingernail analysis of arsenic and mercury in children and adults in a Nicaraguan
gold mining community." Arch Environ Health 59(8): 400-9.
Gold mining can release contaminants, including mercury, into the environment,
and may increase exposure to naturally occurring elements such as arsenic. The
authors investigated environmental and human tissue concentrations of arsenic
and mercury in the gold mining town of Siuna, Nicaragua. The study involved 49
randomly selected households in Siuna, from whom a questionnaire along with
environmental and fingernail samples were collected. Environmental samples
indicated that mercury concentrations in drinking water, although generally low,
were higher near the mine site. Arsenic concentrations were elevated in water
and soil samples, but their distribution was unrelated to the mining site. Mercury
concentrations in fingernail samples were correlated with residential proximity to
the mine, drinking water concentrations, occupation, and, among children, with
soil concentrations. Fingernail arsenic concentrations correlated with drinking
water concentrations among adults who consumed higher levels, and with soil
concentrations among children. Fingernail analysis helped to identify differential
exposure pathways in children and adults. Mercury and arsenic uptake via soil
exposure in children warrants further consideration.
MtBE
Belpoggi, F., M. Soffritti, et al. (1997). "Results of long-term experimental studies on the
carcinogenicity of methyl tert-butyl ether." Ann N Y Acad Sci 837: 77-95.
Methyl-tert-butyl ether (MTBE) was submitted to long-term carcinogenicity
bioassays on Sprague-Dawley rats. The test compound was delivered in olive oil
by stomach tube (gavage), at the doses of 1000, 250, and 0 mg/kg b.w. to
groups of 60 males and 60 females, once daily, 4 times weekly, for 104 weeks.
All animals were kept under control until spontaneous death. MTBE was found to
cause in males an increased incidence of Leydig cell testicular tumors in the
group treated with the higher dose, and in females a dose-related increase of
leukemias, an increase of dysplastic proliferations of lymphoreticular tissues, and
also an increase of uterine sarcomas at the lower tested dose. On the basis of
the presented data, MTBE must be considered a potential carcinogen.
Emerging Issues108
Belpoggi, F., M. Soffritti, et al. (1995). "Methyl-tertiary-butyl ether (MTBE)--a gasoline
additive--causes testicular and lymphohaematopoietic cancers in rats." Toxicol Ind
Health 11(2): 119-49.
In the framework of a series of experiments conducted to evaluate the
carcinogenic effects of oxygenated gasoline additives, MTBE was analyzed in an
oral lifetime carcinogenicity study using 8-week-old male and female SpragueDawley rats. These experiments were part of a large research project on
gasoline carcinogenicity performed at the Bentivoglio (BT) Castle Cancer
Research Center of the Ramazzini Foundation and of the Bologna Institute of
Oncology, MTBE, dissolved in oil, was administered by stomach tube at the
doses of 1000, 250, or 0 mg/kg b.w., once daily, four days weekly, for 104
weeks. The animals were maintained until natural death. The last animal died
166 weeks after the start of the experiment, i.e., at 174 weeks of age. Under the
tested experimental conditions, MTBE was shown to cause an increase in Leydig
interstitial cell tumors of the testes and a dose-related increase in lymphomas
and leukemias in female rats.
Borghoff, S. J., J. E. Murphy, et al. (1996). "Development of physiologically based
pharmacokinetic model for methyl tertiary-butyl ether and tertiary-butanol in male
Fisher-344 rats." Fundam Appl Toxicol 30(2): 264-75.
Methyl tertiary-butyl ether (MTBE) and its metabolite tertiary-butanol (TBA) both
cause renal tumors in chronically exposed male rats. Knowledge of the kinetic
behavior of MTBE and TBA in rats and its comparison to the kinetics of these
chemicals in humans will aid in assessing human risk. The objective of this study
was to develop a physiologically based pharmacokinetic (PBPK) model for MTBE
and TBA in rats that will form the basis for a human model. Physiological
parameters such as blood flows, tissue volumes, and alveolar ventilation were
obtained from the literature. Chemical-specific parameters such as the solubility
of MTBE and TBA in blood and selected tissues and metabolic rate constants to
describe whole-body metabolism of MTBE in rats were measured using vial
equilibration and gas uptake techniques, respectively. MTBE metabolism was
described in the model as occurring through two saturable pathways. The model
was able to predict gas uptake data (100 to 2000 ppm starting concentrations)
and levels of MTBE in blood of rats exposed to MTBE by inhalation (400 to 8000
ppm, 6 hr), i.v. (40 mg/kg), and oral (40 or 400 mg/kg) administration. Two
different models to describe the dosimetry of TBA in a rat were tested for their
ability to predict TBA blood levels after MTBE exposure. TBA blood levels were
predicted best at low MTBE exposure concentrations using a two-compartment
model. The pharmacokinetics of TBA appear to be far more complex than those
of MTBE, and additional experimental data on TBA distribution and elimination
will be necessary to refine the submodel. With a quantitative description of the
important determinants of MTBE and TBA dosimetry understood, a better
assessment of the potential toxic and cancer risk for humans exposed to MTBE
can be made.
Emerging Issues109
Casanova, M. and H. A. Heck (1997). "Lack of evidence for the involvement of
formaldehyde in the hepatocarcinogenicity of methyl tertiary-butyl ether in CD-1 mice."
Chem Biol Interact 105(2): 131-43.
The oxygenated fuel additive methyl tertiary-butyl ether (MTBE) induced
hepatocellular adenomas in female but not male CD-1 mice exposed to 8000
ppm; liver cancer was not induced in female or male mice exposed to 3000 or
400 ppm. Since MTBE is metabolized by cytochrome P450 to formaldehyde
(HCHO), a potentially mutagenic intermediate capable of forming DNA-protein
cross-links (DPX), the formation of DPX and of another HCHO derivative, RNAformaldehyde adducts (RFA), from MTBE was investigated using freshly isolated
hepatocytes from female CD-1 mice incubated with MTBE-(O-methyl-14C). DPX
and RFA were detected, but the adduct yields were very small and were
independent of the concentration of MTBE in the hepatocyte suspension over a
wide concentration range (0.33-6.75 mM). Similar results were obtained using
hepatocytes from male B6C3F1 mice and male F344 rats. Induction of
cytochrome P450 by pretreatment of mice with MTBE prior to isolation of
hepatocytes did not result in a measurable increase in the yields of either DPX or
RFA. In contrast to the absence of concentration-dependent DPX and RFA
formation from MTBE, there was a marked, concentration-dependent increase in
the yields of both DPX and RFA when [14C]formaldehyde was added directly to
the medium. These results suggest that the metabolism of MTBE to HCHO
approaches saturation at concentrations below 0.33 mM, and that the rate of
HCHO production from metabolism of MTBE is slow relative to the rate of HCHO
metabolism. The lack of concentration dependence and the absence of species
or sex differences in the formation of DPX and RFA from MTBE indicate that
metabolism of MTBE to HCHO is not a critical component of its carcinogenic
mechanism in mice.
Cruzan, G., S. J. Borghoff, et al. (2007). "Methyl tertiary-butyl ether mode of action for
cancer endpoints in rodents." Regul Toxicol Pharmacol 47(2): 156-65.
There are no reports of studies that evaluate if methyl tertiary-butyl ether (MTBE)
exposure causes cancer in humans. This evaluation of MTBE carcinogenicity is
based on the results of animal studies. A weak tumorigenic response was
reported for both MTBE and TBA in one tumor type (kidney) in male rats, for
MTBE in one other tumor type (testicular) in male rats, for MTBE in one tumor
type (liver) in female mice, and for TBA in one tumor type (thyroid) in female
mice. The weight of the evidence does not support a genotoxic mode of action
(MOA). Non-genotoxic MOAs have been demonstrated or suggested that
correspond to the weak tumorigenic responses. These MOAs either do not occur
in humans or humans are much less susceptible to these effects. It is, therefore,
unlikely that humans would be exposed to sufficient levels of MTBE to cause
these tumorigenic responses.
de Peyster, A., K. J. MacLean, et al. (2003). "Subchronic studies in Sprague-Dawley
rats to investigate mechanisms of MTBE-induced Leydig cell cancer." Toxicol Sci 72(1):
31-42.
Emerging Issues110
High MTBE exposures caused rat Leydig cell (LC) tumors in inhalation and
gavage cancer bioassays. Investigating early endocrine changes consistent with
known mechanisms of LC carcinogenesis, we gavaged adult male SpragueDawley rats with MTBE in five different subchronic experiments and studied
testosterone biosynthesis in isolated rat LCs exposed in vitro to MTBE or a major
metabolite, t-butanol. In vitro LC testosterone production declined 29-50%
following 3-h exposures to 50-100 mM MTBE or t-butanol. Within hours after
gavaging with 1,000 or 1,500 mg/kg MTBE, circulating testosterone declined to
38-49% of control (p < 0.05). If sampled longer after treatment or with lower
doses, testosterone reductions were less dramatic or nondetectable even after
28 days of treatment. Accessory organ:brain weight ratios decreased only slightly
although showing dose response with 40-800 mg/kg/day after 28 days. High
MTBE doses caused slight liver weight and total P450 increases. Reduced
aromatase activity in liver and testis microsomes predicted low serum estradiol,
but estradiol was 19% higher than corn oil controls concurrent with testosterone
reduction 1 h after the last of 14 daily 1,200-mg/kg doses (p < 0.05). Pituitary
luteinizing hormone (LH) and prolactin measured in both intact and
orchiectomized rats, with testosterone implants in some castrated rats providing
stable levels of testosterone, revealed no consistent direct effect on
hypothalamic-pituitary function. MTBE-treated rat livers showed no evidence of
peroxisome proliferation, a characteristic of some LC carcinogens. Considering
recognized mechanisms of Leydig cell cancer in rats, collectively these results
suggested reduced LC steroidogenesis enzyme activity as a possible mechanism
underlying MTBE LC carcinogenesis.
Iavicoli, I., G. Carelli, et al. (2002). "Methyl-tertiary-butyl ether (MTBE) inhibits growth
and induces cell transformation in rodent fibroblasts." Anticancer Res 22(4): 2173-7.
Methyl-tertiary-butyl ether (MTBE) is a ubiquitous oxygen-bearing additive used
to reduce engine knocking and obtain cleaner gasoline combustion. Conflicting
data have been reported about a possible carcinogenic role of MTBE in humans.
In this study we evaluated the effects of MTBE on cell growth and transformation
in rodent fibroblasts. We found that MTBE inhibits cell proliferation in a dose- and
time-dependent pattern with an IC50 of about 0.84 mM. We also studied the
effects of MTBE on cell cycle distribution. The most striking effect was a
reduction in the percentage of cells in the G2/M-phase which was associated
with an increase of cells in the S-phase of the cell cycle, as assessed by flow
cytometry. At a dose corresponding to IC50, a subdiploid peak indicative of
apoptosis, was also evident. MTBE was also able to induce cell transformation in
vitro. In conclusion, our results suggest that MTBE can affect cell growth and
induce cell transformation in cultured rodent fibroblasts.
Mehlman, M. A. (1990). "Dangerous properties of petroleum-refining products:
carcinogenicity of motor fuels (gasoline)." Teratog Carcinog Mutagen 10(5): 399-408.
Gasoline contains large numbers of dangerous and cancer-causing chemicals
such as benzene, butadiene, toluene, ethylbenzene, xylene, trimethyl pentane,
methyltertbutylether (MTBE) and many others. For the U.S. alone approximately
Emerging Issues111
140 billion gallons of gasoline were consumed in 1989. An increase in only ten
cents per gallon in price of gasoline generates 14 billion dollars in extra profit per
year for oil industry cartel. Laboratory animals exposed to gasoline developed
cancers in different tissues and organs. A number of epidemiological studies in
humans provide evidence of increased cancer risk of leukemia, kidney, liver,
brain, lymphosarcoma, lymphatic tissue pancreas and other tissues and organs.
Mehlman, M. A. (1996). "Dangerous and cancer-causing properties of products and
chemicals in the oil-refining and petrochemical industry--Part XXII: Health hazards from
exposure to gasoline containing methyl tertiary butyl ether: study of New Jersey
residents." Toxicol Ind Health 12(5): 613-27.
Methyl tertiary butyl ether has caused the following cancers in rats and mice:
kidney, testicular, liver, lymphomas, and leukemias. Thus, in the absence of
adequate data on humans, it is biologically plausible and prudent to regard
methyl tertiary butyl ether-for which there is sufficient evidence of carcinogenicity
in experimental animals-as a probable human carcinogen. This means that some
humans are at extreme risk of contracting cancers resulting from their exposure
to oxygenated gasoline containing methyl tertiary butyl ether. Immediately after
the introduction of methyl tertiary butyl ether into gasoline, many consumers of
this product in New Jersey, New York, Alaska, Maine, Pennsylvania, Colorado,
Arizona, Montana, Massachusetts, California, and other areas, experienced a
variety of neurotoxic, allergic, and respiratory illnesses. These illnesses were
similar to those suffered by refinery workers from the Oil, Chemical, and Atomic
Workers Union who mixed methyl tertiary butyl ether with gasoline. Additionally,
these illnesses occurred following exposure to extremely low levels of methyl
tertiary butyl ether in gasoline, particularly when compared to the adverse health
effects that occurred only after exposure to very high levels of conventional
gasoline. Thus, gasoline containing methyl tertiary butyl ether exhibited
substantially more toxicity in humans than gasoline without this additive. A
number of oil industry-sponsored or influenced reports alleged that these
illnesses were either unrelated to exposure to reformulated gasoline or were
characteristic of some yet-to-be-identified communicable disease. These studies
further alleged that the widespread concern was not about illness, but was
merely a reaction to the odor and the five cent increase in the price of gasoline.
To clarify the significance of this issue, it is important to note that consumers
have been using gasoline for many decades, with complaints only occurring
following exposure to high levels at 100s ppm or higher. After the introduction of
methyl tertiary butyl ether gasoline there were thousands of human health
complaints. The sudden increase in widespread illnesses from which many
thousands of individuals throughout the United States began to suffer
immediately following the introduction of methyl tertiary butyl ether into gasoline
provides strong and unquestionable evidence that gasoline containing methyl
tertiary butyl ether is associated with human illnesses. When considering the
severity of the illnesses in humans, it is prudent that this highly dangerous
chemical be promptly removed from gasoline and comprehensive studies be
Emerging Issues112
conducted to assess the long-term effects that human may experience in the
future from past and current exposure.
Mehlman, M. A. (1998). "Hazardous pollutant: gasoline containing methyl tertiary-butyl
ether (MTBE)." Int J Occup Environ Health 4(2): 134-5.
Mehlman, M. A. (1999). "Cancer risk from exposure to motor fuel containing MTBE:
"reasonably anticipated to be a human carcinogen"." Int J Occup Environ Health 5(4):
323-4.
Mehlman, M. A. (2002). "Carcinogenicity of methyl-tertiary butyl ether in gasoline." Ann
N Y Acad Sci 982: 149-59.
Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale
in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that
time, numerous reports have appeared describing adverse health effects of
individuals exposed to MTBE, both from inhalation of fumes in the workplace and
while pumping gasoline. Leakage of MTBE, a highly water-soluble compound,
from underground storage tanks has led to contamination of the water supply in
many areas of the United States. Legislation has been passed by many states to
prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has
not accomplished its stated goal of decreasing air pollution, and it has posed
serious health risks to a large portion of the population, particularly the elderly
and those with respiratory problems, asthma, and skin sensitivity. Reports of
animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to
the widespread introduction of MTBE into gasoline. These reports were largely
ignored. In ensuing years, further studies have shown that MTBE causes various
types of malignant tumors in mice and rats. The National Toxicology Program
(NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met
in December 1998 to consider listing MTBE as "reasonably anticipated to be a
human carcinogen." In spite of recommendations from Dr. Bailer, the primary
reviewer, and other scientists on the committee, the motion to list MTBE in the
report was defeated by a six to five vote, with one abstention. On the basis of
animal studies, it is widely accepted that if a chemical is carcinogenic in
appropriate laboratory animal test systems, it must be treated as though it were
carcinogenic in humans. In the face of compelling evidence, NTP Committee
members who voted not to list MTBE as "reasonably anticipated to be a human
carcinogen" did a disservice to the general public; this action may cause
needless exposure of many to health risks and possibly cancers.
Mennear, J. H. (1997). "Carcinogenicity studies on MTBE: critical review and
interpretation." Risk Anal 17(6): 673-81.
Chronic inhalation of toxic concentrations of MTBE caused renal tubular cell
neoplasms in male Fischer 344 rats and hepatocellular adenomas in female CD1 mice. In Sprague-Dawley rats the oral administration of MTBE was associated
with increased incidences of Leydig cell tumors and of lymphomas and
leukemias (combined) in males and females, respectively. Neither lymphomas
Emerging Issues113
nor leukemias were individually increased in treated females. leydig cell tumors
are common in rats and do not predict human responses to drugs and chemicals.
Neither MTBE nor its metabolite, t-butyl alcohol, possess mutagenic potential
and a second metabolite, formaldehyde, is mutagenic in vitro but in vivo results
are equivocal. MTBE-induced neoplasms are most likely produced through a
nongenetic mechanism which requires chronic exposure to toxic doses. Because
of the intense odor (and taste) of MTBE, humans will not tolerate either air or
water concentrations sufficient to produce the cytotoxic precursors required to
promote cellular proliferation.
Moser, G. J., B. A. Wong, et al. (1996). "Methyl tertiary butyl ether lacks tumorpromoting activity in N-nitrosodiethylamine-initiated B6C3F1 female mouse liver."
Carcinogenesis 17(12): 2753-61.
Methyl tertiary butyl ether (MTBE) is an additive in some formulations of
unleaded gasoline (UG) that enhances octane and reduces carbon monoxide
emissions from motor vehicles. MTBE in CD-1 mice and UG in B6C3F1 mice
increased the incidence of liver tumors selectively in female mice in their chronic
bioassays. Both agents were negative in in vitro tests of genotoxicity, and exhibit
similar hepatic microsomal cytochrome P450 activity and hepatocyte proliferation
after short-term exposure. We previously demonstrated that UG has hepatic
tumor-promoting activity in DEN-initiated female B6C3F1 mice. Thus, we
hypothesized that MTBE would have hepatic tumor-promoting activity in the
same initiation-promotion model system in which UG was a hepatic tumor
promoter. Twelve-day-old female B6C3F1 mice were initiated with a single i.p.
injection of the mutagen N-nitrosodiethylamine (DEN) (5 mg DEN/kg, 7.1 ml/kg
body weight) or saline. Beginning at 8 weeks of age, mice were exposed to 0
ppm or the hepatocarcinogenic dose of approximately 8000 ppm MTBE. After
subchronic exposure, MTBE significantly increased liver weight and hepatic
microsomal cytochrome P450 activity without hepatotoxicity or an increase in
non-focal hepatocyte DNA synthesis. These are subchronic effects similar to
those produced by UG. However, MTBE did not significantly increase the mean
size of hepatic foci and volume fraction of the liver occupied by foci as compared
to DEN-initiated controls at either 16 or 32 weeks. The lack of tumor-promoting
ability of MTBE in DEN-initiated female mouse liver was unexpected and
suggests that MTBE does not produce liver tumors through a tumor-promoting
mechanism similar to that of UG.
Snelling, J., M. O. Barnett, et al. (2006). "Methyl tertiary hexyl ether and methyl tertiary
octyl ether as gasoline oxygenates: assessing risks from atmospheric dispersion and
deposition." J Air Waste Manag Assoc 56(10): 1484-92.
Methyl tertiary hexyl ether (MtHxE) and methyl tertiary octyl ether (MtOcE) are
currently being developed as replacement oxygenates for methyl tertiary butyl
ether (MtBE) in gasoline. As was the case with MtBE, the introduction of these
ethers into fuel supplies guarantees their introduction into the environment as
well. In this study, a screening-level risk assessment was performed by
comparing predicted environmental concentrations (PEC) of these ethers to
Emerging Issues114
concentrations that might cause adverse effects to humans or ecosystems. A
simple box model that has successfully estimated urban air concentrations of
MtBE was adapted to predict atmospheric concentrations of MtHxE and MtOcE.
Expected atmospheric concentrations of these ethers were also estimated using
the European Union System for the Evaluation of Substances (EUSES)
multimedia fate model, which simultaneously calculates PECs in the various
environmental compartments of air, water, soil, and sediment. Because little or
no data are available on the physicochemical, environmental, and toxicological
properties of MtHxE and MtOcE, estimation methods were used in conjunction
with EUSES to predict both the PECs and the concentrations at which these
ethers might pose a threat. The results suggest that these ethers would
contaminate the air of a moderately sized U.S. city (Boston, MA) at levels similar
to those found previously for MtBE. The risk assessment module in EUSES
predicted risk characterization ratios of 10(-3) and 10(-2) for MtHxE and MtOcE,
respectively, in Boston, and 10(-2) and 10(-1) in very large urban centers,
suggesting that these ethers pose only a minimal threat to ecosystems at the
anticipated environmental concentrations. The assessment also indicates that
these compounds are possible human carcinogens and that they may be present
in urban air at concentrations that pose an unacceptable cancer risk. Therefore,
testing of the toxicological properties of these compounds is recommended
before they replace MtBE in gasoline.
Spitzer, H. L. (1997). "An analysis of the health benefits associated with the use of
MTBE reformulated gasoline and oxygenated fuels in reducing atmospheric
concentrations of selected volatile organic compounds." Risk Anal 17(6): 683-91.
To assess the health benefits gained from the use of cleaner burning gasoline,
an analysis was conducted of changes in the atmospheric concentration of eight
VOCs: acetaldehyde, benzene, 1,3-butadiene, ethylbenzene, formaldehyde,
POM, toluene, and xylenes resulting from the use of reformulated gasoline and
oxyfuel containing the additive MTBE. Modeled ambient air concentrations of
VOCs were used to assess three seasonally-based scenarios: baseline gasoline
compared to (a) summer MTBE:RFG, (b) winter MTBE:RFG, and (c) MTBE
oxyfuel. The model predicts that the addition of MTBE to RFG or oxyfuel will
decrease acetaldehyde, benzene, 1,3-butadiene and POM, but increase
formaldehyde tailpipe emissions. The increased formaldehyde emissions,
however, will be offset by the reduction of formaldehyde formation in the
atmosphere from other VOCs. Using a range of plausible risk estimates, the
analysis predicts a positive health benefit, i.e., a decline in cancer incidence
associated with use of MTBE:RFG and MTBE oxyfuel. Using EPA cancer risk
estimates, reduction in 1,3-butadiene exposure accounts for the greatest health
benefit while reduction of benzene exposure accounts for the greatest health
benefits based on alternative risk estimates. An analysis of microenvironment
monitoring data indicates that most exposures to VOCs are significantly below
levels of concern based on established margin-of-safety standards. The analysis
does suggest, however, that health effects associated with short-term exposures
to acetaldehyde and benzene may warrant further investigation.
Emerging Issues115
Pesticides
"NEW STUDIES CHALLENGE PESTICIDE SAFETY." (2006). Ecologist 36(2): 9-9.
The article focuses on three new studies that challenge pesticide safety. A study
published in the journal Occupational and Environmental Medicine showed that
when pregnant women and children are exposed to pesticides and insect sprays,
the risk of childhood cancer doubles. Researchers of the journal Epidemiology
took urine samples from several males undergoing treatment for low sperm
counts and discovered that a by-product of the pesticide chlorpyrifos could be
causing fertility problems. Scientists at Berkeley University in California
conducted a study that showed that extremely low levels of pesticides kill frogs.
"Quebec bans 2,4-D." (2006/6/1). Environmental Science & Technology 40(11): 34473447.
The article reports on the implementation of the third phase of the Pesticides
Management Code in Quebec in 2006, which resulted in the ban against the use
of 2,4-D, a popular herbicide in lawn and garden products. The 2,4-D herbicide is
banned due to concerns that it is linked to the onset of childhood cancer. The
Pesticides Management Code is considered the toughest environmental
regulation in North America and results in the ban of 20 active ingredients used
for cosmetic applications in gardens and lawns. The article reports on the
implementation of the third phase of the Pesticides Management Code in
Quebec in 2006, which resulted in the ban against the use of 2,4-D, a popular
herbicide in lawn and garden products. The 2,4-D herbicide is banned due to
concerns that it is linked to the onset of childhood cancer. The Pesticides
Management Code is considered the toughest environmental regulation in North
America and results in the ban of 20 active ingredients used for cosmetic
applications in gardens and lawns
Turf Pesticides and Cancer Risk Database (2007). Cornell University College of
Veterinary Medicine Program on Breast Cancer and Environmental Risk Factors.
Search the database three ways to find the cancer-causing potential of active
ingredients in turf pesticide products.
Adler, Tina (2003/11). "Methyl Bromide Ups Prostate Risk." Environmental Health
Perspectives 111(14): A754-A754.
Cites the result of a study pertaining to relationship between exposure to
common agricultural pesticides and eventual development of prostate cancer in
Iowa and North Carolina. Role of methyl bromide in causing prostate cancer;
Comparison of risk levels between men exposed to pesticides and the general
population; Plan to assess the link between lung cancer and pesticide use.
Alavanja, Michael and Matthew Bonner (2005). "Pesticides and Human Cancers."
Cancer Investigation 23(8): 700-711.
The potential for human carcinogenicity of almost all pesticides currently on the
market has been poorly evaluated and is inadequately understood. Generating
Emerging Issues116
mechanistic data in both animal studies and epidemiology will play an
increasingly important role in the future. Improved exposure assessment, in large
prospective studies that generate reliable exposure-response data that focus on
individual pesticide exposures are needed. One of the greatest opportunities to
make more rapid progress will be to foster more multi-disciplinary collaborations
between toxicologists and epidemiologists. Collaborations on molecular
epidemiology investigations offers such opportunities to both toxicologists and
epidemiologists that were not possible even a decade ago.
Barrett, Julia R. (2006/9). "Pyrethroids in the Home." Environmental Health
Perspectives 114(9): A544-A544.
The article reports on the results from the Children's Pesticide Exposure Study,
an investigation of pesticide exposures among 23 children aged 3-11 in Seattle,
Washington, which showed that residential use of pyrethroids appears to be a
more significant source of exposure to pyrethroid pesticides than diet.
Pyrethroids may affect neurological development, disrupt hormones, induce
cancer and suppress the immune system. Researchers at the Emory University
and the Centers for Disease Control and Prevention determined urinary
pyrethroid metabolite levels during 15 consecutive days for each child.
Researchers conclude that an organic diet is unlikely to dramatically decrease a
child's exposure to pyrethroids the way it does exposure to organophosphorus
pesticides
Belson, Martin, Beverely Kingsley and Adrianne Holmes (2007/1). "Risk Factors for
Acute Leukemia in Children: A Review." Environmental Health Perspectives 115(1):
138-145.
Although overall incidence is rare, leukemia is the most common type of
childhood cancer. It accounts for 30% of all cancers diagnosed in children
younger than 15 years. Within this population, acute lymphocytic leukemia (ALL)
occurs approximately five times more frequently than acute myelogenous
leukemia (AML) and accounts for approximately 78% of all childhood leukemia
diagnoses. Epidemiologic studies of acute leukemias in children have examined
possible risk factors, including genetic, infectious, and environmental, in an
attempt to determine etiology. Only one environmental risk factor (ionizing
radiation) has been significantly linked to ALL or AML. Most environmental risk
factors have been found to be weakly and inconsistently associated with either
form of acute childhood leukemia. Our review focuses on the demographics of
childhood leukemia and the risk factors that have been associated with the
development of childhood ALL or AML. The environmental risk factors discussed
include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides,
alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular
risk factors can be used to support measures to reduce potentially harmful
exposures and decrease the risk of disease. We also review genetic and
infectious risk factors and other variables, including maternal reproductive history
and birth characteristics.
Emerging Issues117
Boffetta, Paolo (2006/9). "Human cancer from environmental pollutants: The
epidemiological evidence." Mutation Research/Genetic Toxicology & Environmental
Mutagenesis 608(2): 157-162.
Abstract: An increased risk of mesothelioma has been reported among
individuals experiencing residential exposure to asbestos, while results for lung
cancer are less consistent. Several studies have reported an increased risk of
lung cancer risk from outdoor air pollution: on the basis of the results of the
largest study, the proportion of lung cancers attributable to urban air pollution in
Europe can be as high as 10.7%. A causal association has been established
between second-hand tobacco smoking and lung cancer, which may be
responsible for 1.6% of lung cancers. Radon is another carcinogen present in
indoor air, which may be responsible for 4.5% of lung cancers. An increased risk
of bladder might be due to water chlorination by-products. The available
evidence on cancer risk following exposure to other environmental pollutants,
including, pesticides, dioxins and electro-magnetic fields, is inconclusive.
Brechka, Nicole (2006/9). all about organics. Better Nutrition, Active Interest Media, Inc.
68: 6-6.
The article presents the author's views on organic foods and lifestyle. Toxins in
food and environment can damage to one's lifestyle. Pesticides, industrial
pollutants and other chemical compounds can lead to critical health conditions
ranging from cancer to a slow metabolism. The author suggests that adopting an
organic lifestyle can reduce this toxic load on human bodiesThe article presents
the author's views on organic foods and lifestyle. Toxins in food and environment
can damage to one's lifestyle. Pesticides, industrial pollutants and other chemical
compounds can lead to critical health conditions ranging from cancer to a slow
metabolism. The author suggests that adopting an organic lifestyle can reduce
this toxic load on human bodies
Buffler, Patricia A., Marilyn L. Kwan, Peggy Reynolds and Kevin Y. Urayama (2005).
"Environmental and Genetic Risk Factors for Childhood Leukemia: Appraising the
Evidence." Cancer Investigation 23(1): 60-75.
Childhood leukemia is the most common cause of malignancy under the age of
15, representing an annual incidence rate of 43 cases per million in the United
States. Confirmed clinical and epidemiologic associations explain less than 10%
of disease incidence, leaving 90% of cases with an unclear etiology. To
effectively study leukemia in children, one must recognize that this disease has a
multifactorial causal mechanism and a heterogeneous biological composition. In
addition, the timing of environmental exposures and genetic changes related to
disease risk must be considered. This review of both environmental and genetic
risk factors for childhood leukemia evaluates the current published literature and
synthesizes the available knowledge. Furthermore, attention is directed to
expected sources of new advances and the compelling current issues that need
to be addressed before further progress can be made. We discuss parental
occupational exposures, air pollution, other chemical exposures such as
household solvents and pesticides, radiation, dietary factors, immunological
Emerging Issues118
factors, socioeconomic status, and genetic susceptibility. We hope to provide the
reader with an understanding of the challenge and promise that characterizes the
current and future directions in childhood leukemia research
Chen, Zhi, Leslie Robison, Roger Giller, Mark Krailo, Mary Davis, Stella Davies and
Xiao Ou Shu (2006/1). "Environmental exposure to residential pesticides, chemicals,
dusts, fumes, and metals, and risk of childhood germ cell tumors." International Journal
of Hygiene & Environmental Health 209(1): 31-40.
Abstract: We examined relationships between exposure to residential pesticides,
chemicals, dusts, fumes, and metals, and childhood germ cell tumors (GCTs) in
the largest case-control study to date on the topic. We recruited 272 children
under 15 years old who had GCT diagnosed between January 1, 1993 and
December 31, 2001. Controls were selected by random-digit dialing and were
frequency matched to cases by sex, age, and geographic area. Telephone
interviews and self-administered questionnaires of parents were used to collect
exposure information. We used unconditional logistic regression to estimate odds
ratios (OR) and 95% confidence intervals (CI). Maternal and paternal exposure
from 6 months before pregnancy to during breastfeeding and children's postnatal
exposure to residential pesticides were generally unrelated to risk of childhood
GCT. Elevated OR were observed for mothers exposure to hair dyes 1 month
nd during
breastfeeding for boys and girls combined, and for girls (OR=1.5, 95%
for paternal exposure to insecticides more often than four times or exposure to
indoor insecticides mor
Overall this study produced no strong evidence linking parental and child
residential exposure to pesticides, certain chemicals, dusts, fumes, and metals to
increased risk of childhood GCT. Statistically significant associations need to be
confirmed in future studies.
Colt, Joanne S., Mancer J. Cyr, Shelia H. Zahm, Geoffrey S. Tobias and Patricia Hartge
(2007/2). "Inferring Past Pesticide Exposures: A Matrix of Individual Active Ingredients
in Home and Garden Pesticides Used in Past Decades." Environmental Health
Perspectives 115(2): 248-254.
BACKGROUND: In retrospective studies of the health effects of home and
garden pesticides, self-reported information typically forms the basis for exposure
assessment. Study participants generally find it easier to remember the types of
pests treated than the specific pesticides used. However, if the goal of the study
is to assess disease risk from specific chemicals, the investigator must be able to
link the pest type treated with specific chemicals or products. OBJECTIVES: Our
goal was to develop a "pesticide--exposure matrix" that would list active
ingredients on the market for treating different types of pests in past years, and
provide an estimate of the probability that each active ingredient was used.
METHODS: We used several different methods for deriving the active ingredient
lists and estimating the probabilities. These methods are described in this article,
Emerging Issues119
along with a sample calculation and data sources for each. RESULTS: The
pesticide--exposure matrix lists active ingredients and their probabilities of use
for 96 distinct scenarios defined by year (1976, 1980, 1990, 2000), applicator
type (consumer, professional), and pest type (12 categories). Calculations and
data sources for all 96 scenarios are provided online. CONCLUSIONS: Although
we are confident that the active ingredient lists are reasonably accurate for most
scenarios, we acknowledge possible sources of error in the probability estimates.
Despite these limitations, the pesticide--exposure matrix should provide valuable
information to researchers interested in the chronic health effects of residential
pesticide exposure.
Cooney, Maureen A., Julie L. Daniels, Julie A. Ross, Norman E. Breslow, Brad H.
Pollock and Andrew F. Olshan (2007/1). "Household Pesticides and the Risk of Wilms
Tumor." Environmental Health Perspectives 115(1): 134-137.
BACKGROUND: Previous epidemiologic studies have suggested that exposure
to pesticides in utero and during early childhood may increase the risk for
development of childhood cancer, including Wilms tumor, a childhood kidney
tumor. OBJECTIVES: In this analysis we evaluated the role of residential
pesticide exposure in relation to the risk of Wilms tumor in children using data
from a North American case-control study. METHODS: The National Wilms
Tumor Study Group (NWTSG) collected information on exposure to residential
pesticides from the month before pregnancy through the diagnosis reference
date using detailed phone interviews from 523 case mothers and 517 controls
frequency matched on child's age and geographic region and identified by listassisted random digit dialing. Pesticides were grouped according to type of
pesticide and where they were used. RESULTS: A slightly increased risk of
Wilms tumor was found among children of mothers who reported insecticide use
[odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0-1.8; adjusted for
education, income, and the matching variables]. Results from all other categories
of pesticides were generally close to the null. CONCLUSIONS: This study is the
largest case-control study of Wilms tumor to date. We were unable to confirm
earlier reports of an increased risk for Wilms tumor among those exposed to
residential pesticides during pregnancy through early childhood
Fortes, Cristina, Simona Mastroeni, Franco Melchi, Maria Antonietta Pilla, Massimo
Alotto, Gianluca Antonelli, Diana Camaione, Simone Bolli, Elisabetta Luchetti and Paolo
Pasquini (2007/4). "The association between residential pesticide use and cutaneous
melanoma." European Journal of Cancer 43(6): 1066-1075.
Abstract: Occupational pesticide exposure has been linked to cutaneous
melanoma in epidemiological studies. We studied the association between
cutaneous melanoma and the residential use of pesticides. This is a case-control
study of cutaneous melanoma (287 incident cases; 299 controls). Data on
pesticide use was obtained with a standardised interview. An increased risk of
, education, sun
Emerging Issues120
exposure and pigmentary characteristics. Subjects exposed for 10 years or more
exposed for less than 10 years. A dose response was observed for the intensity
of pesticides use (p <sub>trend</sub> =0.027). The results indicate that
residential pesticide exposure may be an independent risk factor for cutaneous
melanoma.
Hughes, Glenys (2006/8). "PESTICIDES AND RISK OF LEUKAEMIA IN CHILDREN."
Journal of Epidemiology & Community Health 60(8): 736-736.
The article reports on the French study linking exposure to different types of
pesticides and risk of contracting leukemia in children. Of the 280 cases and 288
controls studied, it was found out that acute leukemia was significantly linked with
the use by the mother of insecticides in the home and garden during
pregnancyThe article reports on the French study linking exposure to different
types of pesticides and risk of contracting leukemia in children. Of the 280 cases
and 288 controls studied, it was found out that acute leukemia was significantly
linked with the use by the mother of insecticides in the home and garden during
pregnancy
Infante-Rivard, Claire and Scott Weichenthal (2007/1). "Pesticides and Childhood
Cancer: An Update of Zahm and Ward's 1998 Review." Journal of Toxicology &
Environmental Health: Part B 10(1): 81-99.
Children are exposed to pesticides through a number of sources, including
residential and agricultural applications. Parental occupational exposure to
pesticides is also a concern because exposures occurring during pregnancy and
carry-home residues also contribute to children's cumulative burden. A number of
epidemiological studies consistently reported increased risks between pesticide
exposures and childhood leukemia, brain cancer, neuroblastoma, non-Hodgkin's
lymphoma, Wilms' tumor, and Ewing's sarcoma. An extensive review of these
studies was published in 1998 (Zahm & Ward, 1998). Fifteen case-control
studies, 4 cohort studies, and 2 ecological studies have been published since this
review, and 15 of these 21 studies reported statistically significant increased risks
between either childhood pesticide exposure or parental occupational exposure
and childhood cancer. Therefore, one can confidently state that there is at least
some association between pesticide exposure and childhood cancer. However,
an unambiguous mechanistic cause-and-effect relationship between pesticide
exposure and childhood cancer was not demonstrated in these studies, and
modifying factors such as genetic predisposition, rarely considered in the
reviewed studies, likely play an important role. While the time window of
exposure may be a crucial determinant for biological effects associated with
pesticide exposure on children, studies have not contributed definitive
information on the most vulnerable period. Accurate exposure assessment
remains a challenge; future epidemiological studies need to assess geneenvironment interactions and use improved exposure measures, including
separate parental interviews, specific pesticide exposure questions, and
Emerging Issues121
semiquantitative exposure measures that can be used to confirm information
obtained through questionnaires.
Jurewicz, Joanna and Wojciech Hanke (2006/7). "EXPOSURE TO PESTICIDES AND
CHILDHOOD CANCER RISK: HAS THERE BEEN ANY PROGRESS IN
EPIDEMIOLOGICAL STUDIES?" International Journal of Occupational Medicine &
Environmental Health 19(3): 152-169.
Objectives: In Europe and the United States, cancer is a major cause of death
among children aged 5-14 years. The role of environmental exposure to
pesticides in carcinogenesis, although strongly postulated, is still unknown.
Pesticides have been used since the early days of modern agriculture. They are
biologically active compounds, which may pose health risk during or after their
use. Materials and Methods: Epidemiological studies focused on childhood
cancer and exposure to pesticides, conducted over the last seven years, were
identified through searching PUBMED, MEDLINE and EBSCO literature bases.
From each study, the following information was abstracted: type of cancer, type
of exposure, study design, risk estimate, and study population. This review will
try to answer the question on whether any further progress in epidemiology of
childhood cancer due to pesticide exposure has been made. Results: Leukemia,
brain cancer, non-Hodgkin's lymphoma and neuroblastoma are mentioned as
potentially associated with pesticide exposure among children. Despite an
increasing evidence in support of this finding, it is still limited because of the
weakness of research methodology. The substantial weak points of numerous
epidemiological studies of pesticide-related health effects are problems faced in
exposure assessment, small numbers of exposed subjects, a limited number of
studies focused on the majority of cancers, and difficulties in estimating critical
windows of exposure. Conclusion: In the light of existing, although still limited
evidence of adverse effects of pesticide exposure, it is necessary to reduce
exposure to pesticides. The literature review suggests a great need to increase
awareness among people occupationally or environmentally exposed to
pesticides about their potential negative influence on health of their children.
Jurewicz, Joanna, Wojciech Hanke, Carolina Johansson, Christofer Lundqvist, Sandra
Ceccatelli, Peter Van Den Hazel, Margaret Saunders and Rolf Zetterstr+¦m (2006/10).
"Adverse health effects of children's exposure to pesticides: What do we really know
and what can be done about it." Acta Paediatrica 95: 71-80.
Children may be exposed to pesticides in several ways, such as by
transplacental transfer during foetal life, by intake of contaminated breast milk
and other nutrients, or by contact with contaminated subjects and areas in the
environment such as pets treated with insecticides, house dust, carpets and
chemically treated lawns and gardens. Exposure early in life, and particularly
during periods of rapid development, such as during foetal life and infancy, may
have severe effects on child health and development by elevating the risk of
congenital malformations, cancer, malabsorption, immunological dysfunction,
endocrine disease, and neurobehavioural deficiencies. As pesticides can also
interfere with parental reproductive health, exposure of parents may have
Emerging Issues122
consequences for the offspring leading to reduced chance of male birth and
increased risk of childhood cancer. Conclusions: Current knowledge about
tolerable levels and consequences of toxic exposure to pesticides during human
development is rather scarce. Owing to the high risk of exposure to pesticides,
particularly in less developed countries, further elucidation by well-controlled
epidemiological studies in this field it is urgently needed. The Policy Interpretation
Network on Children's Health and Environment (PINCHE), which is financed by
the EU DG research has suggested actions against pesticide exposure. They
have been presented and discussed in this paper. Several suggestions of
PINCHE concerning action needed regarding pesticides were presented in the
paper.
Khanjani, Narges, Jan Lucas Hoving, Andrew Benjamin Forbes and Malcolm Ross Sim
(2007/5). "Systematic Review and Meta-analysis of Cyclodiene Insecticides and Breast
Cancer." Journal of Environmental Science & Health, Part C -- Environmental
Carcinogenesis & Ecotoxicology Reviews 25(1): 23-52.
Cyclodienes are a group of organochlorine pesticides that have been the focus of
increasing numbers of breast cancer etiology studies in recent years. The aim of
this systematic review and meta-analysis was to summarize and pool the results
of breast cancer and cyclodiene insecticide contamination studies. We used
databases from 1966 to 7/2006 and included 21 case-control studies. Pooled
odds ratios or differences in means as geometric means ratios were calculated.
Meta-analysis of the chemicals did not reveal any statistically significant
association except for heptachlor. The heterogeneity among the different studies
and the methodology limitations are discussed.
Marusek, Jennifer C., Myles G. Cockburn, Paul K. Mills and Beate R. Ritz (2006/2).
"Control Selection and Pesticide Exposure Assessment Via GIS in Prostate Cancer
Studies." American Journal of Preventive Medicine 30: S109-S116.
Background: Pesticide exposures have recently been linked to prostate cancer,
but accurate exposure assessment to date has been challenging. Additionally,
historical exposures have rarely been examined. The utility of a geographic
information system (GIS) based model for assessing residential exposure to
pesticides is examined in a population-based case control setting among groups
easily recruited as control subjects. Methods: Historical pesticide and land-use
data were used to generate exposure measures for two distinct pesticides
previously linked to prostate cancer risk for control series and prostate cancer
cases in three rural California counties. Simple estimates of residential
exposures for different exposure periods are compared between case and
control groups and the value of complete residential histories is examined.
Results: Residential exposure to methyl bromide based on current address
resulted in an overestimation of exposure for distant exposure periods, whereas
exposures to organochlorines were similar regardless of availability of historical
residence information. A response bias was detected in Medicare controls such
that unexposed elderly control subjects were characterized by a higher response
rate. Conclusions: The frequency and amount of application of pesticides seem
Emerging Issues123
to affect the bias introduced into GIS-based exposure assessments. Inclusion of
subjects complete residential histories into the computation of exposure
estimates seems to reduce bias from this source, but it may also introduce an
additional bias through control self-selection. The use of randomly sampled
controls from Medicare and residential parcels listings independent of subject
response seems to result in the opportunity for relatively unbiased estimates of
pesticide exposures.
Nasterlack, Michael (2006/9). "Do pesticides cause childhood cancer?" International
Archives of Occupational & Environmental Health 79(7): 536-544.
Objectives: Epidemiological studies have reported associations between
childhood cancer and either parental or child exposure to pesticides. Reviews
have been published in 1997 and 1998, where the evidence was found
suggestive but not conclusive. An update of the current state of knowledge is
warranted. Methods: A literature search has been conducted to identify and
evaluate new research results on this topic issued between 1998 and 2004.
Results: Eighteen new studies have been identified for this review. Collectively,
the studies suggest an increase in the risk of different cancer types associated
with exposure to pesticides. However, the evidence is conflicting with regard to
cancer types as well as to causative factors across studies. The major
shortcomings concern exposure assessment, where, e.g., farming is treated
equal to exposure to pesticides, disregarding other possible exposures, e.g., to
biological or infectious agents, and hitherto unidentified lifestyle factors. Also,
many exposure questionnaires used in case control studies are based on broad
and sometimes implausible categories. In most studies exposures were
categorized as ever vs. never, with no regard for exposure intensity or duration.
Conclusions: The available literature does not allow firm conclusions with regard
to pesticides and any type of childhood cancer. Investing in the acquisition and
critical review of exposure information appears to be the crucial step for causal
assessment in future research. However, focusing on the presence of pesticides,
and not asking the question why they were used, might mask relevant
associations to other causative agents.
Nielsen, Susan Searles, Beth A. Mueller, Anneclaire J. De Roos, Hannah Malia Viernes,
Federico M. Farin and Harvey Checkoway (2005/7). "Risk of Brain Tumors in Children
and Susceptibility to Organophosphorus Insecticides: The Potential Role of
Paraoxonase (PON1)." Environmental Health Perspectives 113(7): 909-913.
Prior research suggests that childhood brain tumors (CBTs) may be associated
with exposure to pesticides. Organophosphorus insecticides (OPs) target the
developing nervous system, and until recently, the most common residential
insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body
through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate
whether two common PON1 polymorphisms, C-108T and Q192R, are associated
with CBT occurrence, we conducted a population-based study of 66 cases and
236 controls using DNA from neonatal screening archive specimens in
Washington State, linked to interview data. The risk of CBT was nonsignificantly
Emerging Issues124
increased in relation to the inefficient PON1 promoter allele [per PON1<sub>108T</sub> allele, relative to PON1<sub>-108CC</sub>: odds ratio (OR) = 1.4;
-value for trend = 0.07]. Notably, this
association was strongest and statistically significant among children whose
mothers reported chemical treatment of the home for pests during pregnancy or
childhood (per PON1<sub>-108T</sub> allele: among exposed, OR = 2.6; 95%
primitive neuroectodermal tumors (per PON1<sub>-108T</sub> allele: OR = 2.4;
PON1 and influences enzyme activity in a substrate-dependent manner, was not
associated with CBT risk, nor was the PON1<sub>C-108T/Q192R</sub>
haplotype. These results are consistent with an inverse association between
PON1 levels and CBT occurrence, perhaps because of PON1's ability to detoxify
OPs common in children's environments. Larger studies that measure plasma
PON1 levels and incorporate more accurate estimates of pesticide exposure will
be required to confirm these observations.
Rekha, S.N. Naik and R. Prasad (2006/11). "Pesticide residue in organic and
conventional food-risk analysis." Journal of Chemical Health & Safety 13(6): 12-19.
During the era of green revolution in the late sixties, introduction of high yielding
varieties, expansion of irrigated areas, increased use of nitrogen, phosphorous,
potassium (N, P and K) fertilizers; chemical pesticides and higher cropping
intensity drove India toward self-sufficiency in food production. Use of chemical
pesticides to control various insects, pests and diseases over the years
destroyed many naturally occurring effective biological agents. Increased
quantities of nutrients and pesticides in agricultural run off waters in recent years
has caused serious problem of water pollution. The ill effects of green revolution
include residues of extensively used chemical pesticides in various
environmental components. Several studies showed that pesticides could cause
health problem such as birth defects, nerve damage and cancer. Keeping in mind
the problem of pesticide residues in various components of environment, the
present study was conducted on different organic farms and market samples
(conventional farms). Four groups of pesticides, i.e., organochlorine, carbamates,
organophosphorous and pyrethrites were analyzed in wheat and rice samples.
Presence of organochlorine pesticide residue was observed in two out of ten
organic farms, which were converted from conventional to organic practices few
years ago. This was attributed to excessive use of synthetic pesticides. Wheat
and rice samples taken from market (conventional farm) showed significant level
of pesticide residues. Method used for extraction of pesticides was validated with
recovery studies, which showed more than 80% recoveries for organochlorine,
organophosphorous, carbamates and pyrithroids, respectively. Pesticide residue
contamination of food was assessed for risk analysis.
Teitelbaum, Susan L., Marilie D. Gammon, Julie A. Britton, Alfred I. Neugut, Bruce Levin
and Steven D. Stellman (2007/3). "Reported Residential Pesticide Use and Breast
Emerging Issues125
Cancer Risk on Long Island, New York." American Journal of Epidemiology 165(6): 643651.
Pesticides, common environmental exposures, have been examined in relation to
breast cancer primarily in occupational studies or exposure biomarker studies.
No known studies have focused on self-reported residential pesticide use. The
authors investigated the association between reported lifetime residential
pesticide use and breast cancer risk among women living on Long Island, New
York. They conducted a population-based case-control study of 1,508 women
newly diagnosed with breast cancer between August 1996 and July 1997 and
1,556 randomly selected, age-frequency-matched controls. Comprehensive
residential pesticide use and other risk factors were assessed by using an inperson, interviewer-administered questionnaire. Unconditional logistic regression
was used to calculate odds ratios and 95% confidence intervals. Breast cancer
risk was associated with ever lifetime residential pesticide use (odds ratio = 1.39,
95% confidence interval: 1.15, 1.68). However, there was no evidence of
increasing risk with increasing lifetime applications. Lawn and garden pesticide
use was associated with breast cancer risk, but there was no dose response.
Little or no association was found for nuisance-pest pesticides, insect repellants,
or products to control lice or fleas and ticks on pets. This study is the first known
to suggest that self-reported use of residential pesticides may increase breast
cancer risk. Further investigation in other populations is necessary to confirm
these findings.
Tsai, James, Wendy E. Kaye and Frank J. Bove (2006/1). "Wilms tumor and exposures
to residential and occupational hazardous chemicals." International Journal of Hygiene
& Environmental Health 209(1): 57-64.
Abstract: This case-control study examines the association between residential
tumor. The study included 303 cases recruited from six state cancer registries,
who were diagnosed between January 1, 1992 and December 31, 1995. A total
of 575 controls selected through random digit dialing were frequency matched to
the cases. A standard questionnaire was administered to participants during a
telephone interview. Parental residential addresses and locations of US
Environmental Protection Agency National Priority List (NPL) sites were
geocoded and analyzed, along with occupational exposure information. There
were no cases of Wilms tumor found in individuals living within one-half mile
distance of a hazardous waste site. However, elevated odds ratios were found
for using hairdressing chemicals, motor oil, paint, paint stripper, and pesticides
during the pregnancy term and during the 2-year period prior to birth. The
findings do not support the hypothesis that Wilms tumor is associated with
residing near an NPL site.
Wigle, Donald T., Tye E. Arbuckle, Mark Walker, Michael G. Wade, Liu Shiliang and
Daniel Krewski (2007/1). "Environmental Hazards: Evidence for Effects on Child
Health." Journal of Toxicology & Environmental Health: Part B 10(1): 3-39.
Emerging Issues126
The human fetus, child, and adult may experience adverse health outcomes from
parental or childhood exposures to environmental toxicants. The fetus and infant
are especially vulnerable to toxicants that disrupt developmental processes
during relatively narrow time windows. This review summarizes knowledge of
associations between child health and development outcomes and environmental
exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs),
dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain
pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air
toxicants (especially particulate matter [PM] and ozone), chlorination disinfection
by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency
(RF) radiation, residential proximity to hazardous waste disposal sites, and
solvents. The adverse health effects linked to such exposures include fetal death,
birth defects, being small for gestational age (SGA), preterm birth, clinically overt
cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic
deficits, childhood cancer, asthma, other respiratory diseases, and acute
poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS,
and certain ambient air toxicants, produce adverse health effects at relatively low
exposure levels during fetal or child developmental time windows. For the many
associations supported by limited or inadequate epidemiologic evidence, major
sources of uncertainty include the limited number of studies conducted on
specific exposure-outcome relationships and methodologic limitations. The latter
include (1) crude exposure indices, (2) limited range of exposure levels, (3) small
sample sizes, and (4) limited knowledge and control of potential confounders.
Important knowledge gaps include the role of preconceptual paternal exposures,
a topic much less studied than maternal or childhood exposures. Large
longitudinal studies beginning before...
Radon
Auvinen, A., L. Salonen, et al. (2005). "Radon and other natural radionuclides in
drinking water and risk of stomach cancer: a case-cohort study in Finland." Int J Cancer
114(1): 109-13.
Very high concentrations of naturally occurring radionuclides are encountered in
Finnish groundwaters and wells. Radon ingested through drinking water can
cause considerable radiation to the stomach. We assessed the effect of natural
uranium and other radionuclides in drinking water on the risk of stomach cancer.
Subjects (n = 144,627) in the base cohort had lived outside the municipal tap
water system during 1967-1980. A subcohort of 4,590 subjects was formed for
use as a reference group by random sampling of the base cohort, with
stratification by age and sex. Within the subcohort, 371 subjects had used
drinking water from drilled wells prior to 1981. Stomach cancer cases within the
subcohort were identified through a cancer registry, and cases using water from
drilled wells were selected. Activity concentrations of radon, radium-226 and
natural uranium in the drinking water were analyzed using radiochemical and
alpha spectrometric methods. The median activity concentration of radon in well
water was 130 Bq/l for both the 88 stomach cancer cases and the 274 subjects in
Emerging Issues127
the subcohort. Median radium concentrations were 0.007 Bq/l for cases and
0.010 Bq/l for the subcohort, with a median uranium concentration of 0.07 Bq/l for
both groups. Risk of stomach cancer was not associated with exposure to radon
or other radionuclides. The hazard ratio of stomach cancer was 0.68 for radon
(95% CI 0.29-1.59 at 100 Bq/l water), 0.69 per Bq/1 for radium-226 (95% CI
0.33-1.47) and 0.76 per Bq/1 for uranium (95% CI 0.48-1.21). Our results do not
indicate an increased risk of stomach cancer from ingestion of radon or other
natural radionuclides through drinking water at these exposure levels.
Boffetta, P. and F. Nyberg (2003). "Contribution of environmental factors to cancer risk."
Br Med Bull 68: 71-94.
Environmental carcinogens, in a strict sense, include outdoor and indoor air
pollutants, as well as soil and drinking water contaminants. An increased risk of
mesothelioma has consistently been detected among individuals experiencing
residential exposure to asbestos, whereas results for lung cancer are less
consistent. At least 14 good-quality studies have investigated lung cancer risk
from outdoor air pollution based on measurement of specific agents. Their results
tend to show an increased risk in the categories at highest exposure, with relative
risks in the range 1.5-2.0, which is not attributable to confounders. Results for
other cancers are sparse. A causal association has been established between
exposure to environmental tobacco smoke and lung cancer, with a relative risk in
the order of 1.2. Radon is another carcinogen present in indoor air which may be
responsible for 1% of all lung cancers. In several Asian populations, an increased
risk of lung cancer is present in women from indoor pollution from cooking and
heating. There is strong evidence of an increased risk of bladder, skin and lung
cancers following consumption of water with high arsenic contamination; results
for other drinking water contaminants, including chlorination by-products, are
inconclusive. A precise quantification of the burden of human cancer attributable
to environmental exposure is problematic. However, despite the relatively small
relative risks of cancer following exposure to environmental carcinogens, the
number of cases that might be caused, assuming a causal relationship, is
relatively large, as a result of the high prevalence of exposure.
Boudette, E. L. (1994). "Radon in New Hampshire." GEO-2 Retrieved June 2, 2007,
2007, from http://www.des.state.nh.us/factsheets/geo/geo-2.htm.
Healthy New Hampshire. (2007). "Environmental Health: Radon." Retrieved June 2,
2007, from http://www.healthynh2010.org/radon.htm.
The mission of Healthy New Hampshire 2010 is to inspire action and focus
resources, engaging private and public partners, to improve the quality of life and years of healthy life - for the New Hampshire public.
Kendall, G. M. and T. J. Smith (2005). "Doses from radon and its decay products to
children." J Radiol Prot 25(3): 241-56.
This paper considers doses from radon and decay products when inhaled or
ingested by one year old infants and by ten year old children. Doses from decay
Emerging Issues128
products deposited on skin are also discussed. For inhalation and ingestion, the
general pattern of doses to organs is broadly similar to that in adults. Much the
largest doses are received by the organ of intake (respiratory tract and stomach
respectively). Otherwise, tissues with higher fat content tend to receive
somewhat higher doses from radon gas than other tissues. Dose coefficients
(dose per unit intake factors) for children are generally larger than those for
adults. However, total annual doses are more similar across the age groups
because of smaller intakes of air and water by children. Radon decay products
deposited on skin may be able to induce skin cancer. However, the location of
the sensitive cells is not known with certainty and they may lie too deep to
receive significant dose. If they are irradiated, it is likely that doses to children
would be larger than for adults. The radiological significance of doses to children
is discussed.
Kennedy, C. A., A. M. Gray, et al. (2002). "The cost-effectiveness of residential radon
remediation programmes: assumptions about benefits stream profiles over time." J
Environ Radioact 59(1): 19-28.
A recent cost-effectiveness analysis of a residential radon remediation
programme considered and highlighted many areas of uncertainty in the
parameters chosen for the analysis. One assumption not challenged in the study
was the benefits stream profile adopted. There are several different ways of
loading the benefits in terms of life years into the cost-effectiveness model and
several of these are explored and the results are reported in this study. The
benefits profile depends upon the lead-time to cancer manifestation post
environmental carcinogen (radon) exposure. The literature reviewed suggests
that there are many options for loading benefits to radon-induced lung cancer
prevention programmes. In this study, the alternative benefits stream profiles are
explored and their implications for the cost-effectiveness ratio are examined.
Adopting different benefits stream profiles to the model results in a range of costeffectiveness ratios from 14912.90 pounds per life year gained to 52416.27
pounds per life year gained. The preferred model is reported where the life years
gained are assumed to be equally distributed over the last 15 years of the 40year time horizon of the analysis (Y25-40) and the corresponding costeffectiveness ratio is 37,943 pounds per life year gained.
Krewski, D., J. H. Lubin, J. M. Zielinski, M. Alavanja, V. S. Catalan, R. W. Field, J. B.
Klotz, E. G. Letourneau, C. F. Lynch, J. L. Lyon, D. P. Sandler, J. B. Schoenberg, D. J.
Steck, J. A. Stolwijk, C. Weinberg and H. B. Wilcox (2006). "A combined analysis of
North American case-control studies of residential radon and lung cancer." J Toxicol
Environ Health A 69(7): 533-97.
Cohort studies have consistently shown underground miners exposed to high
levels of radon to be at excess risk of lung cancer, and extrapolations based on
those results indicate that residential radon may be responsible for nearly 1015% of all lung cancer deaths per year in the United States. However, casecontrol studies of residential radon and lung cancer have provided ambiguous
evidence of radon lung cancer risks. Regardless, alpha-particle emissions from
Emerging Issues129
the short-lived radioactive radon decay products can damage cellular DNA. The
possibility that a demonstrated lung carcinogen may be present in large numbers
of homes raises a serious public health concern. Thus, a systematic analysis of
pooled data from all North American residential radon studies was undertaken to
provide a more direct characterization of the public health risk posed by
prolonged radon exposure. To evaluate the risk associated with prolonged
residential radon exposure, a combined analysis of the primary data from seven
large scale case-control studies of residential radon and lung cancer risk was
conducted. The combined data set included a total of 4081 cases and 5281
controls, representing the largest aggregation of data on residential radon and
lung cancer conducted to date. Residential radon concentrations were
determined primarily by a-track detectors placed in the living areas of homes of
the study subjects in order to obtain an integrated 1-yr average radon
concentration in indoor air. Conditional likelihood regression was used to
estimate the excess risk of lung cancer due to residential radon exposure, with
adjustment for attained age, sex, study, smoking factors, residential mobility, and
completeness of radon measurements. Although the main analyses were based
on the combined data set as a whole, we also considered subsets of the data
considered to have more accurate radon dosimetry. This included a subset of the
data involving 3662 cases and 4966 controls with a-track radon measurements
within the exposure time window (ETW) 5-30 yr prior to the index date
considered previously by Krewski et al. (2005). Additional restrictions focused on
subjects for which a greater proportion of the ETW was covered by measured
rather than imputed radon concentrations, and on subjects who occupied at most
two residences. The estimated odds ratio (OR) of lung cancer generally
increased with radon concentration. The OR trend was consistent with linearity (p
= .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits
(-0.01, 0.26). For the subset of the data considered previously by Krewski et al.
(2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our
criteria (residential stability and completeness of radon monitoring) expected to
improve radon dosimetry led to increased estimates of the EOR. For example, for
subjects who had resided in only one or two houses in the 5-30 ETW and who
had a-track radon measurements for at least 20 yr of this 25-yr period, the EOR
was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the
EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of
the miner data. Collectively, these results provide direct evidence of an
association between residential radon and lung cancer risk, a finding predicted
by extrapolation of results from occupational studies of radon-exposed
underground miners.
Kurttio, P., L. Salonen, et al. (2006). "Well water radioactivity and risk of cancers of the
urinary organs." Environ Res 102(3): 333-8.
Water from bedrock frequently contains higher concentrations of natural
radionuclides than water from other sources. Bladder and kidneys receive a
radiation dose when radioactive isotopes are excreted into urine. The subjects for
this case-cohort study were selected from all drilled wells users in Finland. The
Emerging Issues130
study comprised 61 bladder cancer and 51 kidney cancer cases diagnosed
between 1981 and 1995, as well as a random sample of 274 reference persons,
stratified by age and sex. The median activity concentrations of radon in drilled
wells used by bladder and kidney cancer cases and the reference cohort were
170, 140, and 130 Bq/L, respectively. The radium concentration was 0.01 Bq/L
for all groups and the uranium concentrations were 0.08, 0.07, and 0.06 Bq/L,
respectively. The bladder cancer risks associated with radon, radium, and
uranium activity concentrations in drinking water were 1.02 (0.68-1.54) per
log(100 Bq of radon/L), 0.73 (0.21-2.50) per log(0.1 Bq of radium/L), and 0.77
(0.32-1.89) per log(1 Bq of uranium/L). The corresponding figures for kidney
cancer were 0.81 (0.47-1.37), 0.12 (0.01-1.10), and 0.92 (0.36-2.35),
respectively. In conclusion, even though ingested radionuclides from drilled wells
are a source of radiation exposure, they are not associated with a substantially
increased risk of bladder or kidney cancers in concentrations occurring in drilled
wells.
New Hampshire Department of Environmental Services. (2005). "Radon in Air and
Water: An Overview For The Homeowner " WD-WSEB-3-12 Retrieved June 2, 2007,
2007, from http://des.state.nh.us/factsheets/ws/ws-3-12.htm.
Riesenfeld, E. P., T. W. Marcy, et al. (2007). "Radon awareness and mitigation in
Vermont: a public health survey." Health Phys 92(5): 425-31.
Radon exposure is associated with an increased incidence of lung cancer, and
elevated levels may be found in as many as 1 out of 15 homes. The U.S. EPA
recommends testing homes for radon and mitigating over the advisory level of 4
picocuries per liter (4 pCi L(-1), or 148 Bq m(-3)). A sample population from a list
of Vermont residents who had tested their residence for radon through the
Vermont Department of Health and who had elevated levels were mailed a
survey to assess demographic characteristics, knowledge about radon, mitigation
rates, types of mitigation, as well as barriers to mitigation. The response rate was
63%. Forty-three percent of respondents mitigated. Roughly half were not
completely knowledgeable of radon based upon the ability to associate radon
exposure with lung cancer risk. Reasons not to mitigate radon levels in homes
were cost and lack of concern over elevated levels. A multivariate logistic
regression analysis revealed factors associated with mitigating: an education
level of college or higher (p = 0.02), concern that a high radon level would affect
real estate value (p = 0.04), and home age less than 10 y (p = 0.05). In summary,
less than half of Vermonters with elevated radon levels participating in the
Department of Health program mitigated. We identify factors associated with
radon mitigation that may lead to improved radon education and mitigation
practice.
Samet, J. M. (2006). "Residential radon and lung cancer: end of the story?" J Toxicol
Environ Health A 69(7): 527-31.
The earliest evidence of increased lung cancer risk associated with radon came
largely from studies of highly exposed underground miners. In the United States,
Emerging Issues131
concerns about residential exposures became prominent in the early 1980s with
the identification of the Watras home, which had remarkably elevated radon
concentrations. By then, the problem of indoor radon was already recognized in
Europe and the first epidemiological studies on indoor radon had been reported.
The concern about the risk of indoor radon motivated a series of case-control
studies of residential radon and lung cancer in the United States, Canada, China,
and a number of European countries. In 1999, the U.S. National Research
Council Committee on the Biological Effects of Ionizing Radiation (BEIR VI)
weighed the scientific evidence available at that time on this issue and concluded
that residential radon was an important contributor to the lung cancer burden and
that risks were appropriately estimated by a linear nonthreshold model. Since
individual case-control studies have not provided consistent direct evidence of
excess lung cancer risk at residential exposure levels, combined analyses of
residential radon studies have been undertaken in both North America and
Europe. These combined analyses, including the North American pooled analysis
described in this issue, represent an important complement to the findings of the
miner studies and further support the linear no-threshold model for cancer risk
adopted by the BEIR VI Committee and other groups.
Steck, D. J. and R. W. Field (2006). "Dosimetric challenges for residential radon
epidemiology." J Toxicol Environ Health A 69(7): 655-64.
Radon concentration alone may not be an adequate surrogate to measure for
lung cancer risk in all residential radon epidemiologic lung cancer studies. The
dose delivered to the lungs per unit radon exposure can vary significantly with
exposure conditions. These dose-effectiveness variations can be comparable to
spatial and temporal factor variations in many situations. New technologies that
use surface-deposited and implanted radon progeny activities make more
accurate dose estimates available for future epidemiologic studies.
Takahashi, M. and S. Kojima (2006). "Suppression of atopic dermatitis and tumor
metastasis in mice by small amounts of radon." Radiat Res 165(3): 337-42.
We examined the effect of radon in two experimental disease models in mice by
administering radon dissolved in water at 68-203 Bq/liter. Administration of radon
in drinking water to NC/Nga mice significantly delayed the progression of atopic
dermatitis-like skin lesions induced by picrylchloride when administered prior to
the induction of disease signs. The number of pulmonary metastatic foci in
C57BL/6 mice inoculated with B16 melanoma cells was also reduced significantly
by administration of radon in drinking water when the number of tumor cells was
small and the radon treatment was started prior to tumor inoculation. The ratio of
Ifng to Il4 produced by splenocytes from BALB/c mice immunized with DNPAscaris was significantly increased by administration of radon in drinking water.
From these results, a modulation of immunity by radon was suggested.
Wood, W. W., T. F. Kraemer, et al. (2004). "Radon (222Rn) in ground water of fractured
rocks: a diffusion/ion exchange model." Ground Water 42(4): 552-67.
Emerging Issues132
Ground waters from fractured igneous and high-grade sialic metamorphic rocks
frequently have elevated activity of dissolved radon (222Rn). A chemically based
model is proposed whereby radium (226Ra) from the decay of uranium (238U)
diffuses through the primary porosity of the rock to the water-transmitting fracture
where it is sorbed on weathering products. Sorption of 226Ra on the fracture
surface maintains an activity gradient in the rock matrix, ensuring a continuous
supply of 226Ra to fracture surfaces. As a result of the relatively long half-life of
226Ra (1601 years), significant activity can accumulate on fracture surfaces. The
proximity of this sorbed 226Ra to the active ground water flow system allows its
decay progeny 222Rn to enter directly into the water. Laboratory analyses of
primary porosity and diffusion coefficients of the rock matrix, radon emanation,
and ion exchange at fracture surfaces are consistent with the requirements of a
diffusion/ion-exchange model. A dipole-brine injection/withdrawal experiment
conducted between bedrock boreholes in the high-grade metamorphic and
granite rocks at the Hubbard Brook Experimental Forest, Grafton County, New
Hampshire, United States (42 degrees 56'N, 71 degrees 43'W) shows a large
activity of 226Ra exchanged from fracture surfaces by a magnesium brine. The
226Ra activity removed by the exchange process is 34 times greater than that of
238U activity. These observations are consistent with the diffusion/ion-exchange
model. Elutriate isotopic ratios of 223Ra/226Ra and 238U/226Ra are also
consistent with the proposed chemically based diffusion/ion-exchange model.
Zielinski, J. M., Z. Carr, D. Krewski and M. Repacholi (2006). "World Health
Organization's International Radon Project." J Toxicol Environ Health A 69(7): 759-69.
Following initial in vitro and in vivo studies and important studies of uranium
miners, scientists have now completed impressive case-control studies of lung
cancer risk from exposure to residential radon. Researchers have pooled these
studies, in which all the information from the individual studies was reanalyzed.
These pooled analyzes confirm that in the context of residential exposure, radon
is now an established risk factor for lung cancer. Many of the initial uncertainties
have been reduced, and health risk assessors are now confident that radon may
contribute to as much as 10% of the total burden of lung cancer--that is, 2% of all
cancers in the population, worldwide. To reduce residential radon lung cancer
risk, national authorities must have methods and tools based on solid scientific
evidence and sound public health policies. To meet these needs, the World
Health Organization (WHO) has initiated the WHO International Radon Project.
This three year project, to be implemented during the period 2005-2008, will
include (1) a worldwide database on national residential radon levels, radon
action levels, regulations, research institutions, and authorities; (2) public health
guidance for awareness-raising and mitigation; and (3) an estimation of the
global burden of disease (GDB) associated with radon exposure.
Other Pollutants
Emerging Issues133
Gaylor, DW, SJ Culp, LS Goldstein and FA Beland (2000). "Cancer risk estimation for
mixtures of coal tars and benzo(a)pyrene." Risk Analysis 20(1): 81-85.
Two-year chronic bioassays were conducted by using B6C3F1 female mice fed
several concentrations of two different mixtures of coal tars from manufactured
gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain
estimates of cancer potency of coal tar mixtures, by using conventional
regulatory methods, for use in manufactured gas waste site remediation. A
secondary purpose was to investigate the validity of using the concentration of a
single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative
risk for a coal tar mixture. The study has shown that BaP dominates the cancer
risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In
this case the most sensitive tissue site is the forestomach. Using low-dose linear
extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x
10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on
forestomach tumors. If the BaP concentration in the coal tar mixture is less than
6,300 ppm, the more likely case, then lung tumors provide the largest estimated
upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no
contribution of BaP to lung tumors. The upper limit of the cancer potency (slope
factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram
per kg body weight per day from this Good Laboratory Practice (GLP) study
compared with the current value of 7.3 x 10(-3) per microgram per kg body
weight per day listed in the U.S. EPA Integrated Risk Information System.
Harper, J. W. (2007/03/29). "Chemical biology: A degrading solution to pollution."
Nature 446(7135): 499-500.
The article discusses the affect of dioxins generated from rubbish incineration
and industrial processes on human health. The dangerous pollutants which enter
through the food chain from animals, disrupt the human endocrine system
resulting in birth defects, infertility and cancer. The molecular mechanism by
which dioxins regulate steroid signaling thus disturbing the endocrine signaling is
discussed.
Melber, Christine, Janet Kielhorn and Inge Mangelsdorf. (2004). "Concise International
Chemical Assessment Document 62: COAL TAR CREOSOTE." Retrieved July 1,
2007, from http://www.inchem.org/documents/cicads/cicads/cicad62.htm#1.0.
New Hampshire Department of Health and Human Services Bureau of Health Risk
Assessment and Agency for Toxic Substances and Disease Registry. (2000, June 12,
2007). "PUBLIC HEALTH ASSESSMENT: MESSER STREET MANUFACTURED GAS
PLANT, LACONIA, BELKNAP COUNTY, NEW HAMPSHIRE
", from http://www.atsdr.cdc.gov/hac/PHA/messer/msm_toc.html.
The Messer Street Manufactured Gas Plant Site is located in Laconia, New
Hampshire, just to the north of the Messer Street bridge over the Winnipesaukee
River. Between approximately 1860 and 1952, the site was occupied by a facility
that produced gas for lighting and heating from coal. Coal tar, a byproduct of this
process, has been found beneath the site and in the sediments of the
Emerging Issues134
Winnipesaukee River. Since 1994, the New Hampshire Department of Health
and Human Services (DHHS) has been providing advice to the Department of
Environmental Services (DES) on questions of health risk at the site. During that
time, a number of neighboring residents have expressed health concerns about
the contamination at the site. To address these concerns, DHHS completed this
public health assessment for the site under its cooperative agreement with the
U.S. Agency for Toxic Substances and Disease Registry.
Emerging Issues135
Diet and Nutrition
General
Baggiani, C., L. Anfossi, et al. (2007/5). "Solid phase extraction of food contaminants
using molecular imprinted polymers." Analytica Chimica Acta 591(1): 29-39.
Abstract: Food contamination from natural or anthropogenic sources poses
severe risks to human health. It is now largely accepted that continuous
exposure to low doses of toxic chemicals can be related to several chronic
diseases, including some type of cancer and serious hormonal dysfunctions.
Contemporary analytical methods have the sensitivity required for contamination
detection and quantification, but direct application of these methods on food
samples can be rarely performed. In fact, the matrix introduces severe
disturbances, and analysis can be performed only after some clean-up and
preconcentration steps. Current sample pre-treatment methods, mostly based on
the solid phase extraction technique, are very fast and inexpensive but show a
lack of selectivity, while methods based on immunoaffinity extraction are very
selective but expensive and not suitable for harsh environments. Thus,
inexpensive, rapid and selective clean-up methods, relaying on intelligent
materials are needed. Recent years have seen a significant increase of the
molecularly imprinted solid phase extraction (MISPE) technique in the food
contaminant analysis. In fact, this technique seems to be particularly suitable for
extractive applications where analyte selectivity in the presence of very complex
and structured matrices represents the main problem. In this review, several
applications of MISPE in food contamination analysis will be discussed, with
particular emphasis on the extraction of pesticides, drugs residua, mycotoxins
and environmental contaminants.
Brechka, N. (2006/9). all about organics. Better Nutrition, Active Interest Media, Inc. 68:
6-6.
The article presents the author's views on organic foods and lifestyle. Toxins in
food and environment can damage to one's lifestyle. Pesticides, industrial
pollutants and other chemical compounds can lead to critical health conditions
ranging from cancer to a slow metabolism. The author suggests that adopting an
organic lifestyle can reduce this toxic load on human bodiesThe article presents
the author's views on organic foods and lifestyle. Toxins in food and environment
can damage to one's lifestyle. Pesticides, industrial pollutants and other chemical
compounds can lead to critical health conditions ranging from cancer to a slow
metabolism. The author suggests that adopting an organic lifestyle can reduce
this toxic load on human bodies
BBC News. (2007). "Sausage additive linked to cancer." from
http://news.bbc.co.uk/2/hi/health/6286834.stm.
Emerging Issues136
Chicago Tribune. (2007, July 10, 2007). "Meat-sweet diet linked to breast cancer." from
http://featuresblogs.chicagotribune.com/features_julieshealthclub/2007/07/meat-sweetdiet.html.
A ‘Western’ diet of red meat, starches and sweets increases breast cancer risk in
postmenopausal Chinese women, according to a study in the July issue of
Cancer Epidemiology, Biomarkers and Prevention.
Dai, J., J. D. Patel and R. J. Mumper (2007). "Characterization of blackberry extract and
its antiproliferative and anti-inflammatory properties." J Med Food 10(2): 258-65.
Blackberries are rich in polyphenols, including anthocyanins. Polyphenols are
hypothesized to have biological activities that may impact positively on human
health. In these studies, an anthocyanin-rich extract from Hull blackberries grown
in Kentucky was obtained and fully characterized in terms of total anthocyanin
and phenolic content, polymeric color, anthocyanin composition, and total
antioxidant capacity. In vitro cell culture studies showed that the blackberry
extract inhibited HT-29 colon tumor cell growth in a concentration-dependent
manner with 49.2 microg of total anthocyanins/mL inhibiting HT-29 cell growth up
to 66% at 72 hours. Likewise, in a concentration-dependent manner, total
anthocyanin concentrations in the range of 0-40 microg/mL suppressed both
high-dose (10 microg/mL) and low-dose (0.1 microg/mL) lipid A-induced
interleukin-12 release from mouse bone marrow-derived dendritic cells. These
results suggest that Hull blackberry extract (HBE) has potent antioxidant,
antiproliferative, and anti-inflammatory activities and that HBE-formulated
products may have the potential for the treatment and/or prevention of cancer
and/or other inflammatory diseases.
Gonzalez, Carlos A. and Jordi Salas-Salvado (2006). "The potential of nuts in the
prevention of cancer." British Journal of Nutrition 96(1, Suppl. 2): S87-S94.
Cancer is a disease that is characterized by the loss of genetic control over cell
growth and proliferation, mainly as a result of the exposure to environmental
factors. Cessation of smoking and a high consumption of fruits and vegetables
are the most important means of reducing the risk of cancer in our society. Like
fruits and vegetables, nuts are a source of vegetable protein, monounsaturated
fatty acids, vitamin E, phenolic compounds, selenium, vegetable fibre, folic acid
and phytoestrogens. There are numerous mechanisms of action by which these
components can intervene in the prevention of cancer, although they have not
been fully elucidated. There are very few epidemiological studies analyzing the
relationship between nuts consumption and risk of cancer. One of the greatest
difficulties in interpreting the results is that the consumption of nuts, seeds and
legumes are often presented together. The most commonly studied location is
the colon/rectum, an organ in which the effect of nuts is biologically plausible.
Although the results are not conclusive, a protective effect on colon and rectum
cancer is possible. Likewise, some studies show a possible protective effect on
prostate cancer, but there is insufficient data on other tumour locations. New
epidemiological studies are required to clarify the possible effects of nuts on
cancer, particularly prospective studies that make reliable and complete
Emerging Issues137
estimations of their consumption and which make it possible to analyse their
effects independently of the consumption of legumes and seeds.
Hu, Frank B. (2003). "The Mediterranean Diet and Mortality- Olive Oil and Beyond." N
ENGL J MED 348(26): 2595-2596.
The concept of the Mediterranean diet originated from the Seven Countries
Study initiated by Ancel Keys in the 1950s. The study showed that, despite a
high fat intake, the population of the island of Crete in Greece had very low rates
of coronary heart disease and certain types of cancer and had a long life
expectancy. The traditional dietary patterns typical of Crete, much of the rest of
Greece, and southern Italy in the early 1960s were considered to be largely
responsible for the good health observed in these regions.
Keck, Anna-Sigrid, Qingyan Qiao and Elizabeth H. Jeffery (2003). "Food Matrix Effects
on Bioactivity of Broccoli-Derived Sulforaphane in Liver and Colon of F344 Rats " J.
Agric. Food Chem. 51(11): 3320-3327.
Sulforaphane (SF) is considered to be the major anticarcinogenic component in
broccoli. The effects of feeding rats purified SF (5 mmol/kg of diet), broccoli
containing SF formed in situ during laboratory hydrolysis (broccoli-HP; 20%
freeze-dried broccoli diet, 0.16 mmol of SF/kg of diet), and broccoli containing
intact glucosinolates (broccoli-GS; 20% freeze-dried broccoli diet, 2.2 mmol of
glucoraphanin/kg of diet) were compared. Rats (male F344 rats, five per group)
were fed control (modified AIN-76 B-40), SF, broccoli-HP, or broccoli-GS for 5
days. In rats fed broccoli-GS, quinone reductase activities (QR) in the colon and
liver were greater (4.5- and 1.4-fold over control, respectively) than in rats fed
broccoli-HP (3.2- and 1.1-fold over control, respectively). Broccoli-GS and SF
diets increased QR to the same extent, even though the broccoli-GS diet
contained far less SF (as the unhydrolyzed glucosinolate, glucoraphanin) than
the purified SF diet. In a second experiment, rats were fed one of six diets for 5
days: (1) control; (2) 20% broccoli-GS; (3) diet 2 + low SF (0.16 mmol/kg of diet);
(4) diet 2 + high SF (5 mmol/kg of diet); (5) low SF (0.32 mmol/kg of diet); or (6)
high SF (5.16 mmol/kg of diet). In both liver and colon, QR was increased most
by high SF plus broccoli-GS; individually, high SF and broccoli-GS had similar
effects, and adding the low-dose SF to broccoli-GS had either no effect or a
negative effect. In both experiments, urinary SF-mercapturic acid correlated with
QR activity, not with dietary intake. It was concluded that all diets were
substantially more effective in the colon than in the liver and that broccoli-GS was
more potent than SF or broccoli-HP.
Knoops, Kim T. B., Lisette C. P. G. M. de Groot, Daan Kromhout, Anne-Elisabeth
Perrin, Olga Moreiras-Varela, Alessandro Menotti and Wija A. van Staveren (2004).
"Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly Men and
Women: The HALE Project." JAMA 292(12): 1433-1439.
Context Dietary patterns and lifestyle factors are associated with mortality from
all causes, coronary heart disease, cardiovascular diseases, and cancer, but few
studies have investigated these factors in combination.
Emerging Issues138
Objective To investigate the single and combined effect of Mediterranean diet, being
physically active, moderate alcohol use, and nonsmoking on all-cause and
cause-specific mortality in European elderly individuals.
Design, Setting, and Participants The Healthy Ageing: a Longitudinal study in Europe
(HALE) population, comprising individuals enrolled in the Survey in Europe on
Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy,
the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men
and 832 women, aged 70 to 90 years in 11 European countries. This cohort
study was conducted between 1988 and 2000.
Main Outcome Measures Ten-year mortality from all causes, coronary heart disease,
cardiovascular diseases, and cancer.
Results During follow-up, 935 participants died: 371 from cardiovascular diseases, 233
from cancer, and 145 from other causes; for 186, the cause of death was
unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95%
confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI,
0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR,
0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality
(HRs controlled for age, sex, years of education, body mass index, study, and
other factors). Similar results were observed for mortality from coronary heart
disease, cardiovascular diseases, and cancer. The combination of 4 low risk
factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total,
lack of adherence to this low-risk pattern was associated with a population
attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease,
61% from cardiovascular diseases, and 60% from cancer.
Conclusion Among individuals aged 70 to 90 years, adherence to a Mediterranean diet
and healthful lifestyle is associated with a more than 50% lower rate of all-causes
and cause-specific mortality.
Meyer, Catherine (2004). "Scientists Probe Role of Vitamin D: Deficiency a Significant
Problem, Experts Say." JAMA 292(12): 1416-1418.
Vitamin D has received increasing attention over the past few years- with good
reason. A surprising number of people of all ages worldwide have suboptimal
levels of this vitamin. Low levels may lead to unexplained diffuse body pains and
a variety of other symptoms and may also contribute to serious health problems
that only become apparent years later.
Schwartz, GG and HG. Skinner (2007). "Vitamin D status and cancer: new insights." 10
1(6-11).
PURPOSE OF REVIEW: The aim of this article is to describe recent
developments in human studies of the role of vitamin D in the etiology and
treatment of cancer. RECENT FINDINGS: Epidemiologic studies over the past
year lend additional support for important roles for vitamin D in the natural history
of several cancers. Studies showing risk reduction by vitamin D in prostate, colon
and breast cancers were joined by new analyses of endometrial, skin, and
pancreatic cancers. Interest in vitamin D has extended to examinations of its
influence on premalignant conditions such as adenomatous polyps and breast
Emerging Issues139
density. Studies of vitamin D and cancer survival have featured prominently in
the recent literature. Sun exposure and indicators of high vitamin D status were
found to be associated with improved survival for cutaneous melanoma,
Hodgkin's lymphoma, and cancers of the lung, breast, prostate and colon.
Therapeutic trials of vitamin D are especially prominent in the treatment of
prostate cancer. SUMMARY: Studies over the past year indicate potentially
important roles for vitamin D in cancer prevention, survival and treatment.
Shigemura, K., J. L. Arbiser, S. Y. Sun, M. Zayzafoon, P. A. Johnstone, M. Fujisawa, A.
Gotoh, B. Weksler, H. E. Zhau and L. W. Chung (2007). "Honokiol, a natural plant
product, inhibits the bone metastatic growth of human prostate cancer cells." Cancer
109(7): 1279-89.
BACKGROUND: Honokiol, a soluble nontoxic natural product derived from
Magnolia spp., has been shown to induce apoptosis in malignant cells. The effect
of honokiol and the combined therapy with docetaxel on prostate cancer (PCa)
growth and bone metastasis was investigated in experimental models.
METHODS: The in vitro proapoptotic effects of honokiol on human androgendependent and -independent PCa, bone marrow, bone marrow-derived
endothelial, and prostate stroma cells were investigated. Honokiol-induced
activation of caspases was evaluated by Western blot and FACS analysis. To
confirm the cytotoxicity of honokiol, mice bone was inoculated in vivo with
androgen-independent PCa, C4-2 cells and the effects of honokiol and/or
docetaxel on PCa growth in bone were evaluated. Daily honokiol (100 mg/kg)
and/or weekly docetaxel (5 mg/kg) were injected intraperitoneally for 6 weeks.
PCa growth in mouse bone was evaluated by radiography, serum prostatespecific antigen (PSA) and tissue immunohistochemistry. RESULTS: Honokiol
induced apoptosis in all cell lines tested. In PCa cells honokiol induced apoptosis
via the activation of caspases 3, 8, and 9 and the cleavage of poly-adenosine
diphosphate ribose polymerase in a dose- and time-dependent manner. Honokiol
was shown to inhibit the growth and depress serum PSA in mice harboring C4-2
xenografts in the skeleton and the combination with docetaxel showed additive
effects that inhibited further growth without evidence of systemic toxicity.
Immunohistochemical staining confirmed honokiol exhibited growth-inhibitory,
apoptotic, and antiangiogenic effects on PCa xenografts. CONCLUSIONS: The
combination of honokiol and low-dose docetaxel may be used to improve patient
outcome in androgen-independent prostate cancer with bone metastasis.
Vastag, Brian (2004). "FDA Reviews Expanded Claims on Health Benefits of Certain
Foods." Journal of the National Cancer Institute 96(16): 1198-1199.
After 5 years of legal wrangling and U.S. Food and Drug Administration red tape,
food makers may soon be shipping soy products that announce their propensity
for reducing the risk of certain cancers.
Breast Cancer, Diet, & Nutrition
Emerging Issues140
Chagpar, A. B., K. M. McMasters, et al. (2007). "Body Mass Index Influences Palpability
But Not Stage of Breast Cancer at Diagnosis." American Surgeon 73(6): 555-560.
Body mass index (BMI) is associated with breast cancer risk, but its relationship
with stage at diagnosis is unclear. BMI was calculated for patients in the North
American Fareston and Tamoxifen Adjuvant trial, and was correlated with
clinicopathologic factors, including stage at diagnosis. One thousand eight
hundred fourteen patients were enrolled in the North American Fareston and
Tamoxifen Adjuvant study; height and weight were recorded in 1451 (80%) of
them. The median BMI was 27.1 kg/m² (range, 14.7-60.7). The median patient
age was 68 years (range, 42-100); median tumor size was 1.3 cm (range, 0.1-14
cm). One thousand seven hundred ninety-three (99.0%) patients were estrogen
receptor positive, and 1519 (84.7%) were progesterone receptor positive. There
was no significant relationship between BMI (as a continuous variable) and nodal
status (P = 0.469), tumor size (P = 0.497), American Joint Committee on Cancer
stage (P = 0.167), grade (P = 0.675), histologic subtype (P = 0.179), or estrogen
receptor status (P = 0.962). Patients with palpable tumors, however, had a lower
BMI than those with nonpalpable tumors (median 26.4 kg/m² vs 27.5 kg/m², P <
0.001). Similar results were found when BMI was classified as a categorical
variable (<25 vs 25-29.9 vs ≥30). Increased BMI does not lead to a worse stage
at presentation. Obese patients, however, tend to have nonpalpable tumors.
Mammography in this population is especially important.
Pierce, J. P., L. Natarajan, et al. (2007). "Influence of a Diet Very High in Vegetables,
Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer:
The Women's Healthy Eating and Living (WHEL) Randomized Trial." Journal of the
American Medical Association (JAMA) 298(3): 289-298.
Context Evidence is lacking that a dietary pattern high in vegetables, fruit, and
fiber and low in total fat can influence breast cancer recurrence or survival.
Objective To assess whether a major increase in vegetable, fruit, and fiber intake and a
decrease in dietary fat intake reduces the risk of recurrent and new primary
breast cancer and all-cause mortality among women with previously treated early
stage breast cancer.
Design, Setting, and Participants Multi-institutional randomized controlled trial of dietary
change in 3088 women previously treated for early stage breast cancer who
were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and
2000 and followed up through June 1, 2006.
Intervention The intervention group (n = 1537) was randomly assigned to receive a
telephone counseling program supplemented with cooking classes and
newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of
vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake
from fat. The comparison group (n = 1551) was provided with print materials
describing the "5-A-Day" dietary guidelines.
Main Outcome Measures Invasive breast cancer event (recurrence or new primary) or
death from any cause.
Results From comparable dietary patterns at baseline, a conservative imputation
analysis showed that the intervention group achieved and maintained the
Emerging Issues141
following statistically significant differences vs the comparison group through 4
years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake
from fat, –13%. Plasma carotenoid concentrations validated changes in fruit and
vegetable intake. Throughout the study, women in both groups received similar
clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention
group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive
breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.801.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison
group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval,
0.72-1.15; P = .43). No significant interactions were observed between diet group
and baseline demographics, characteristics of the original tumor, baseline dietary
pattern, or breast cancer treatment.
Conclusion Among survivors of early stage breast cancer, adoption of a diet that was
very high in vegetables, fruit, and fiber and low in fat did not reduce additional
breast cancer events or mortality during a 7.3-year follow-up period.
Pierce, J. P., M. L. Stefanick, et al. (2007). "Greater Survival After Breast Cancer in
Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity."
Journal of Clinical Oncology 25(17): 2345-2351.
Purpose: Single-variable analyses have associated physical activity, diet, and
obesity with survival after breast cancer. This report investigates interactions
among these variables.
Patients and Methods: A prospective study was performed of 1,490 women diagnosed
and treated for early-stage breast cancer between 1991 and 2000. Enrollment
was an average of 2 years postdiagnosis. Only seven women were lost to followup through December 2005.
Results: In univariate analysis, reduced mortality was weakly associated with higher
vegetable-fruit consumption, increased physical activity, and a body mass index
that was neither low weight nor obese. In a multivariate Cox model, only the
combination of consuming five or more daily servings of vegetables-fruits, and
accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30
minutes 6 d/wk), was associated with a significant survival advantage (hazard
ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk
associated with these healthy lifestyle behaviors was observed in both obese and
nonobese women, although fewer obese women were physically active with a
healthy dietary pattern (16% v 30%). Among those who adhered to this healthy
lifestyle, there was no apparent effect of obesity on survival. The effect was
stronger in women who had hormone receptor–positive cancers.
Conclusion: A minority of breast cancer survivors follow a healthy lifestyle that includes
both recommended intakes of vegetables-fruits and moderate levels of physical
activity. The strong protective effect observed suggests a need for additional
investigation of the effect of the combined influence of diet and physical activity
on breast cancer survival.
Colon Cancer, Diet, & Nutrition
Emerging Issues142
Dupertuis YM, Meguid MM, Pichard C. (2007). "Colon cancer therapy: new perspectives
of nutritional manipulations using polyunsaturated fatty acids." Current opinions in
nutritional metabolic care 10(4): 427-32.
URPOSE OF REVIEW: Recent advances in the development of new therapeutic
strategies combining conventional adjuvant radio/chemotherapy with nutritional
manipulations with n-3 polyunsaturated fatty acids (PUFAs) are presented.
RECENT FINDINGS: Studies in cell culture and tumour-bearing animals have
reported the ability of long-chain n-3 PUFAs to enhance the cytotoxicity of
several anticancer drugs. In colon cancer, combination of n-3 PUFAs with 5fluorouracil resulted in an additive growth inhibitory effect on different cell lines.
Moreover, recent findings suggest that eicosapentaenoic or docosahexaenoic
acid may be used to enhance tumour radiosensitivity while reducing
mucosal/epidermal radiotoxicity similar to radioprotective agents. The underlying
mechanism is probably mediated through lipid peroxidation because the
antitumour effect of n-3 PUFAs is shared with the n-6 PUFA, arachidonic acid,
and abolished by vitamin E. In vivo, the use of n-3 PUFAs may provide an
additional advantage compared with n-6 PUFAs. Downregulation of eicosanoid
synthesis from cyclooxygenase II may reduce angiogenesis, inflammation and
metastasis induction. SUMMARY: New insights suggest that n-3 PUFAs may
play an important role not only in cancer prevention but also in cancer
management. They may act synergistically with radio/chemotherapy to kill
tumour cells by increasing oxidative stress while reducing angiogenesis,
inflammation and metastasis induction.
Giovannucci E, Michaud D. (2007). "The role of obesity and related metabolic
disturbances in cancers of the colon, prostate, and pancreas." Gastroenterology 132(6):
2208-25.
Recent evidence indicates that obesity and related metabolic abnormalities are
associated with increased incidence or mortality for a number of cancers,
including those of the colon, prostate, and pancreas. Obesity, physical inactivity,
visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent
risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes
mellitus have a higher risk of colon cancer. For prostate cancer, the relationship
to obesity appears more complex. Obesity seems to contribute to a greater risk
of aggressive or fatal prostate cancer but perhaps to a lower risk of
nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus
are at lower risk of developing prostate cancer. Long-standing type 2 diabetes
increases the risk of pancreatic cancer by approximately 50%. Furthermore, over
the past 6 years, a large number of cohort studies have reported positive
associations between obesity and pancreatic cancer. Together with data from
prediagnostic blood specimens showing positive associations between glucose
levels and pancreatic cancer up to 25 years later, sufficient evidence now
supports a strong role for diabetes and obesity in pancreatic cancer etiology. The
mechanisms for these associations, however, remain speculative and deserve
further study. Hyperinsulinemia may be important, but the role of oxidative stress
initiated by hyperglycemia also deserves further attention.
Emerging Issues143
Grant, William B. (2006). "Epidemiology of disease risks in relation to vitamin D
insufficiency." Progress in Biophysics & Molecular Biology 92(1): 65-79.
Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving
increased attention lately for its role in maintaining optimal health. Although the
calcemic effects of vitamin D have been known for about a century, the
noncalcemic effects have been studied intently only during the past two-three
decades. The strongest links to the beneficial roles of UVB and vitamin D to date
are for bone and Muscle conditions and diseases. There is also a preponderance
of evidence from a variety of studies that vitamin D reduces the risk of colon
cancer. with 1000 1 U/day of vitamin D or serum 25-hydroxyvitamin D levels > 33
ng/mL (82 nmol/L) associated with a 50% lower incidence of colorectal cancer.
There is also reasonable evidence that vitamin D reduces the risk of breast, lung,
ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker,
primarily ecologic, evidence for the role of vitamin D in reducing the risk of an
additional dozen types of cancer. There is reasonably strong ecologic and casecontrol evidence that vitamin D reduces the risk of autoimmune diseases
including such as multiple sclerosis and type I diabetes mellitus, and weaker
evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus,
hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts
its effect are generally well understood for the various conditions and diseases
discussed here. (c) 2006 Elsevier Ltd. All rights reserved.
Gutt CN, Brinkmann L, Mehrabi A, Fonouni H, Müller-Stich BP, Vetter G, Stein JM,
Schemmer P, Büchler MW. (2007). "Dietary omega-3-polyunsaturated fatty acids
prevent the development of metastases of colon carcinoma in rat liver." European
journal of cancer ahead of print.
BACKGROUND: Fish oil consisting of omega-3 polyunsaturated fatty acids
(PUFA) seems to reduce the incidence of colon cancer. The effect of PUFAs on
metastasis of colon carcinoma is still unclear. AIM: The study was designed to
examine the effects of a diet rich in omega-3-PUFAs on a model of colorectal
metastasis. METHODS: Thirthy animals (WAG/Rij) were randomly assigned to
receive an omega-3 diet or a control diet to evaluate their effect on tumor growth.
The target male rats (WAG/Rij) were fed a diet containing 15% omega-3-fatty
acids three days before and 28 days after intervention and the control rats
received 15% coconut oil at the same time points. CC 531 cells, a moderately
differentiated colon adenocarcinoma, were injected into the spleen of each rat.
After 28 days of diet, animals were sacrificed. The tumor growth was evaluated
macroscopically and microscopically in liver tissue. The tissue was examined
after immunostaining and the use of monoclonal antibodies. RESULTS: PUFAs
decreased the index of tumor load from 1.54 in the controls to 0.79 in the
treatment group (P = 0.036). While 69.2% of the control animals were tumor
positive, only 21.4% of the target animals showed tumor after omega-3-fatty acid
(P < 0.05). CONCLUSION: We could show that omega-3-fatty acids may
decrease malignant metastatic tumor growth in the liver.
Emerging Issues144
Hu J, Morrison H, Mery L, Desmeules M, Macleod M. (2007). "Diet and vitamin or
mineral supplementation and risk of colon cancer by subsite in Canada." European
journal of cancer prevention 16(4): 275-91.
The study assesses the association of diet and vitamin or mineral
supplementation with risk of proximal or distal colon cancer. Mailed
questionnaires were completed by 1723 newly diagnosed, histologically
confirmed colon cancer cases and 3097 population controls between 1994 and
1997 in seven Canadian provinces. Measurement included information on socioeconomic status, physical activity, smoking habits, alcohol use, diet and vitamin
or mineral supplementation. Odds ratios and 95% confidence intervals were
derived through unconditional logistic regression. Linear regression was used to
examine that dietary factors affect body mass index. The strongest positive
associations between colon cancer risk and increasing total fat intake were
observed for proximal colon cancer in men and for distal colon cancer in both
men and women. Increased consumption of vegetables, fruit and whole-grain
products did not reduce the risk of colon cancer. A modest reduction in distal
colon cancer risk was noted in women who consumed yellow-orange vegetables.
Significant positive associations were observed between proximal colon cancer
risk in men and consumption of red meat and dairy products, and between distal
colon cancer risk in women and total intake of meat and processed meat. We
also saw strong associations between bacon intake and both subsites of colon
cancer in women. When men were compared with women directly by subsite
however, the results did not show a corresponding association. A significantly
reduced risk of distal colon cancer was noted in women only with increasing
intake of dairy products and of milk. Among men and women taking vitamin and
mineral supplements for more than 5 years, significant inverse associations with
colon cancer were most pronounced among women with distal colon cancer.
These findings suggest that dietary risk factors for proximal colon cancer may
differ from those for distal colon cancer.
Kimura Y, Kono S, Toyomura K, Nagano J, Mizoue T, Moore MA, Mibu R, Tanaka M,
Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T,
Takenaka K, Ichimiya H, Imaizumi N. (2007). "Meat, fish and fat intake in relation to
subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study."
Cancer Science 98(4): 590-7.
High intake of red meat has been associated with increased risk of colorectal
cancer in Western countries. There has been much interest in the role of n-3
polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but
epidemiological findings are limited and inconsistent. The objective of our study
was to examine associations of meat, fish and fat intake with risk of colorectal
cancer, paying particular attention to the subsite within the colorectum. Data
were from the Fukuoka Colorectal Cancer Study, a population-based casecontrol study, covering 782 cases and 793 controls. Diet was assessed by
interview, using newly developed personal-computer software for registering
semiquantitative food frequencies. The intake of beef/pork, processed meat, total
fat, saturated fat or n-6 PUFA showed no clear association with the overall or
Emerging Issues145
subsite-specific risk of colorectal cancer. There was an almost significant inverse
association between n-3 PUFA and the risk of colorectal cancer; the covariateadjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median
1.99 g/day) quintile of energy-adjusted intake was 0.74 (95% confidence interval
0.52-1.06, trend P=0.050). The consumption of fish and fish products was
similarly inversely related to the risk although the association was not statistically
significant. These associations were more evident for distal colon cancer;
adjusted odds ratio for the highest versus lowest quintile of n-3 PUFA intake was
0.56 (95% confidence interval 0.34-0.92, trend P=0.02). Our findings do not
support the hypothesis that consumption of red meat increases colorectal cancer
risk but do suggest that high intake of fish may decrease the risk, particularly of
distal colon cancer.
Lee BB, Cha MR, Kim SY, Park E, Park HR, Lee SC. (2007). "Antioxidative and
Anticancer Activity of Extracts of Cherry (Prunus serrulata var. spontanea) Blossoms."
PLant foods and human nutrition ahead of print.
Organic solvent (methanol, ethanol, and acetone) extracts and water extracts of
cherry (Prunus serrulata var. spontanea) blossoms were prepared, and
antioxidant activities of the extracts were evaluated. Methanolic CBE (100
mug/ml) showed the highest total phenol content (104.30 muM), radical
scavenging activity (34.2%), and reducing power (0.391). The effect of CBE on
DNA damage induced by H(2)O(2) in human leukocytes was evaluated by Comet
assay. All CBE was a potent dose dependent inhibitor of DNA damage induced
by 200 muM of H(2)O(2), methanolic CBE showed the most strong inhibition
activity. The methanolic CBE of 500 mug/ml showed 38.8% inhibition against
growth of human colon cancer cell line HT-29. These results indicated that cherry
blossoms could provide valuable bioactive materials.
Mannisto, Satu, Shiaw-Shyuan Yaun, David J. Hunter, Donna Spiegelman, Hans-Olov
Adami, Demetrius Albanes, Piet A. van den Brandt, Julie E. Buring, James R. Cerhan,
Graham A. Colditz, Jo L. Freudenheim, Charles S. Fuchs, Edward Giovannucci, R.
Alexandra Goldbohm, Lisa Harnack, Michael Leitzmann, Marjorie L. McCullough,
Anthony B. Miller, Thomas E. Rohan, Arthur Schatzkin, Jarmo Virtamo, Walter C.
Willett, Alicja Wolk, Shumin M. Zhang and Stephanie A. Smith-Warner (2007). "Dietary
carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies."
American Journal of Epidemiology 165(3): 246-255.
Dietary carotenoids have been hypothesized to protect against epithelial cancers.
The authors analyzed the associations between intakes of specific carotenoids
(alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and
lycopene) and risk of colorectal cancer using the primary data from 11 cohort
studies carried out in North America and Europe. Carotenoid intakes were
estimated from food frequency questionnaires administered at baseline in each
study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident
cases of colorectal cancer were diagnosed among 702,647 participants. The
authors calculated study-specific multivariate relative risks and then combined
them using a random-effects model. In general, intakes of specific carotenoids
Emerging Issues146
were not associated with colorectal cancer risk. The pooled multivariate relative
risks of colorectal cancer comparing the highest quintile of intake with the lowest
ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein +
zeaxanthin intake was the result borderline statistically significant (95%
confidence interval: 0.84, 1.00). The associations observed were generally
similar across studies, for both sexes, and for colon cancer and rectal cancer.
These pooled data did not suggest that carotenoids play an important role in the
etiology of colorectal cancer.
Nilsson U, Johansson M, Nilsson A, Björck I, Nyman M. (2007). "Dietary
supplementation with beta-glucan enriched oat bran increases faecal concentration of
carboxylic acids in healthy subjects." european journal of clinical nutrition ahead of
print.
Background/Objective:Carboxylic acids (CAs), especially butyric acid, have been
suggested to counteract colonic diseases, such as ulcerative colitis and colon
cancer. Colonic formation of CAs can be influenced by the diet, but the
concentrations and pattern formed need to be evaluated for different food
products in humans. To elucidate how the colonic concentration of CAs in
healthy subjects is influenced by dietary supplementation with oat bran, and
whether the concentration varies over time and during consecutive
days.Subjects/Methods:Twenty-five healthy subjects (age 24+/-1.3) were
recruited to the study. The subjects were given 40 g beta-glucan enriched oat
bran per day, corresponding to 20 g dietary fibre, in 4 slices of bread. CAs were
analysed in faeces during three consecutive days after 0, 4, 8 and 12 weeks on
this diet.Results:The concentration of acetic, propionic, butyric, isobutyric and
isovaleric acid was higher (P<0.05-0.001) after 8 weeks on the oat bran diet as
compared with values at entry, whereas that of lactic acid was lower (P<0.05).
After 12 weeks, the concentrations of acetic, propionic and isobutyric acid were
still higher and that of lactic acid lower. The variation between individuals was
considerable, whereas in the same individuals there was little
variation.Conclusions:Oat bran increased the faecal concentration of CAs after 8
weeks, indicating an increased concentration also in the distal colon. The
concentration of all main acids increased, except for lactic acid, which
decreased. Oat bran may therefore have a preventive potential adjunct to colonic
diseases.European Journal of Clinical Nutrition advance online publication, 23
May 2007; doi:10.1038/sj.ejcn.1602816.
Nutra USA. (2007). "National Cancer Institute funds study using Beneo." from
http://www.nutraingredients-usa.com/news/ng.asp?n=77844-orafti-national-cancerinstitute-beneo.
A study using an inulin, Beneo is being conducted to determine if this supplement
can be used as a prevention method, as colon cancer has ties with being
affected by diet.
Emerging Issues147
Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, Ohnuma T,
Matsushita S.. (2007). "Soy product consumption and the risk of colon cancer: a
prospective study in takayama, Japan." Nutritional Cancer 57(2): 151-7.
The relationship of the intake of soy products and the incidence of colon cancer
was prospectively evaluated in a population-based cohort study in Japan. The
total intake of soy products and isoflavones in a daily diet was estimated from a
validated questionnaire administered at the baseline. The participation rate of the
questionnaire was 92.0%. The participants were followed from 1992 to 2000, and
colon cancer diagnoses were identified at the main hospitals in the study area. In
the analysis, 13,894 men and 16,327 women were included. The medians for
energy-adjusted soy product intake were 85.52 g/day for men and 79.60 g/day
for women. During follow-up, 111 men and 102 women were diagnosed with
colon cancer. A Cox-proportional hazard model was applied to assess the risk of
colon cancer incidence. Among women, the risk was reduced with an increased
soy product consumption; the hazard ratio in the highest tertile was 0.56 (95% CI
0.34-0.92) compared as the lowest tertile (trend: P = 0.04), after adjusting for
multiple potential confounders. Among men, no significant association was
observed. Our results exhibited the weak benefit of soy foods only among
women. Further research to confirm our results may be beneficial.
O'Keefe, Stephen J. D., Dan Chung, Nevine Mahmoud, Antonia R. Sepulveda,
Mashudu Manafe, Judith Arch, Haytham Adada and Tian van der Merwe (2007). "Why
do African Americans get more colon cancer than native Africans?" Journal of Nutrition
137(1, Suppl. S): 175S-182S.
The incidence of colorectal cancer (CRC) is dramatically higher in African
Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. < 1:100,000) and
slightly higher than in Caucasian Americans (CAs). To explore whether the
difference could be explained by interactions between diet and colonic bacterial
flora, we compared randomly selected samples,of healthy 50- to 65-y-old AAs (n
= 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and
colonic metabolism by breath hydrogen and methane responses to oral lactulose.
Fecal samples were cultured for 7-alpha dehydroxylating bacteria and
Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure
proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01)
protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d),
meat, saturated fat, and cholesterol. However, they also consumed more (P <
0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath
hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony
counts of 7-alpha Dehydroxylating bacteria were higher and of Lactobacilli were
lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8
+/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC
risk and mucosal proliferation rates in AAs than in NAs were associated with
higher dietary intakes of animal products and higher colonic populations of
potentially toxic hydrogen and secondary bile-salt-producing bacteria. This
supports our hypothesis that CRC risk is determined by interactions between the
external (dietary) and internal (bacterial) environments.
Emerging Issues148
Rafter, Joseph, Michael Bennett, Giovanna Caderni, Yvonne Clune, Roisin Hughes,
Pernilla C. Karlsson, Annett Klinder, Micheal O'Riordan, Gerald C. O'Sullivan, Beatrice
Pool-Zobel, Gerhard Rechkemmer, Monika Roller, Ian Rowland, Maddalena Salvadori,
Herbert Thijs, Jan Van Loo, Bernhard Watzl and John K. Collins (2007). "Dietary
synbiotics reduce cancer risk factors in polypectomized and colon cancer patients."
American Journal of Clinical Nutrition 85(2): 488-496.
Background: Animal studies suggest that prebiotics and probiotics exert
protective effects against tumor development in the colon, but human data
supporting this suggestion are weak.Objective: The objective was to verify
whether the prebiotic concept (selective interaction with colonic flora of
nondigested carbohydrates) as induced by a synbiotic preparation-oligofructoseenriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and
Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in
humans.Design: The 12-wk randomized, double-blind, placebo-controlled trial of
a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12
was conducted in 37 colon cancer patients and 43 polypectomized patients.
Fecal and blood samples were obtained before, during, and after the
intervention, and colorectal biopsy samples were obtained before and after the
intervention. The effect of synbiotic consumption on a battery of intermediate
biomarkers for colon cancer was examined.Results: Synbiotic intervention
resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus
increased and Clostridium perfringens decreased. The intervention significantly
reduced colorectal proliferation and the capacity of fecal water to induce necrosis
in colonic cells and improve epithelial barrier function in polypectomized patients.
Genotoxicity assays of colonic biopsy samples indicated a decreased exposure
to genotoxins in polypectomized patients at the end of the intervention period.
Synbiotic consumption prevented an increased secretion of interleukin 2 by
peripheral blood mononuclear cells in the polypectomized patients and increased
the production of interferon gamma in the cancer patients.Conclusions: Several
colorectal cancer biomarkers can be altered favorably by synbiotic intervention.
Schatzkin A, Mouw T, Park Y, Subar AF, Kipnis V, Hollenbeck A, Leitzmann MF,
Thompson FE. (2007). "Dietary fiber and whole-grain consumption in relation to
colorectal cancer in the NIH-AARP Diet and Health Study." american journal of clinical
nutrition 85(5): 1353-60.
BACKGROUND: Whether the intake of dietary fiber can protect against
colorectal cancer is a long-standing question of considerable public health
import, but the epidemiologic evidence has been inconsistent. OBJECTIVE: The
objective was to investigate the relation between dietary fiber and whole-grain
food intakes and invasive colorectal cancer in the prospective National Institutes
of Health-AARP Diet and Health Study. DESIGN: The analytic cohort consisted
of 291 988 men and 197 623 women aged 50-71 y. Diet was assessed with a
self-administered food-frequency questionnaire at baseline in 1995-1996; 2974
incident colorectal cancer cases were identified during 5 y of follow-up. The Cox
proportional hazards model was used to estimate the relative risks (RRs) and
Emerging Issues149
95% CIs. RESULTS: Total dietary fiber intake was not associated with colorectal
cancer. The multivariate RR for the highest compared with the lowest intake
quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In
analyses of fiber from different food sources, only fiber from grains was
associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86;
95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely
associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79
(95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association
with whole grain was stronger for rectal than for colon cancer. CONCLUSIONS:
In this large prospective cohort study, total dietary fiber intake was not associated
with colorectal cancer risk, whereas whole-grain consumption was associated
with a modest reduced risk.
Stoner GD, Wang LS, Zikri N, Chen T, Hecht SS, Huang C, Sardo C, Lechner JF.
(2007). "Cancer prevention with freeze-dried berries and berry components." Seminar
Cancer Biology ahead of print.
Our laboratory is developing a food-based approach to the prevention of
esophageal and colon cancer utilizing freeze-dried berries and berry extracts.
Dietary freeze-dried berries were shown to inhibit chemically induced cancer of
the rodent esophagus by 30-60% and of the colon by up to 80%. The berries are
effective at both the initiation and promotion/progression stages of tumor
development. Berries inhibit tumor initiation events by influencing carcinogen
metabolism, resulting in reduced levels of carcinogen-induced DNA damage.
They inhibit promotion/progression events by reducing the growth rate of premalignant cells, promoting apoptosis, reducing parameters of tissue inflammation
and inhibiting angiogenesis. On a molecular level, berries modulate the
expression of genes involved with proliferation, apoptosis, inflammation and
angiogenesis. We have recently initiated clinical trials; results from a toxicity
study indicated that freeze-dried black raspberries are well tolerated in humans
when administered orally for 7 days at a dose of 45g per day. Several Phase IIa
clinical trials are underway in patients at high risk for esophagus and colon
cancer; i.e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to
determine if berries will modulate various histological and molecular biomarkers
of development of these diseases.
Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy
(2007). "Tomato lycopene extract supplementation decreases insulin-like growth factor-I
levels in colon cancer patients." European journal of cancer prevention 16(4): 298-303.
Epidemiological studies have shown that high serum levels of insulin-like growth
factor-I are associated with an increased risk of colon and other types of cancer.
The aim of this study was to determine whether short intervention with dietary
tomato lycopene extract will affect serum levels of the insulin-like growth factor
system components in colon cancer patients. The study had a double-blind,
randomized, placebo-controlled design. Colon cancer patients (n=56), candidates
for colectomy, were recruited from the local community a few days to a few
weeks before surgery. Personal and medical data were recorded. Plasma
Emerging Issues150
concentrations of insulin-like growth factor-I and II and insulin-like growth factor-Ibinding protein-3 were assayed by routine laboratory methods. Lycopene was
assayed by high-performance liquid chromatography. Plasma lycopene levels
increased by twofold after supplementation with tomato lycopene extract. In the
placebo-treated group, there was a small nonsignificant increase in lycopene
plasma levels. The plasma concentration of insulin-like growth factor-I decreased
significantly by about 25% after tomato lycopene extract supplementation as
compared with the placebo-treated group (P<0.05). No significant change was
observed in insulin-like growth factor-I-binding protein-3 or insulin-like growth
factor-II, whereas the insulin-like growth factor-I/insulin-like growth factor-Ibinding protein-3 molar ratio decreased significantly (P<0.05). Given that high
plasma levels of insulin-like growth factor-I have been suggested as a risk factor
for various types of cancer including colon cancer, the results support our
suggestion that tomato lycopene extract has a role in the prevention of colon and
possibly other types of cancer.
Prostate Cancer, Diet, & Nutrition
Alvarez-León EE, Román-Viñas B, Serra-Majem L. (2006). "Dairy products and health:
a review of the epidemiological evidence." The British Journal of Nutrition
96(supplement 1): s94-99.
Evidence-based nutrition is essential to move forward in the science of
community nutrition. The present study is a review of the epidemiological
evidence of dairy products and health. There is an inverse association between
the intake of dairy products and hypertension, stroke and colorectal cancer.
There is no evidence of an association between the consumption of dairy
products and breast cancer. There is some evidence linking high-fat dairy
products and an incremental risk of prostate cancer and weak evidence of the
protective capacity of dairy products on bone health. More prospective studies
should be developed in order to establish better evidence of the relationship
between dairy products and health. Due to the importance of dairy products in
public health nutrition, quantitative recommendations should be established in
the light of the scientific evidence.
Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. (2007). "Fruit, vegetable,
vitamin A intakes, and prostate cancer risk." Prostate Cancer Prostatic ahead of print.
Prostate cancer risk was examined in relation to intakes of fruit, vegetables, betacarotene and retinol. Subjects were a cohort of 1985 men previously to asbestos
who participated in a cancer prevention programme of beta-carotene and retinol
supplements that commenced in July 1990. Diet was assessed at entry to the
programme. Ninety-seven cases of prostate cancer were identified during followup until the end of 2004. A decreased prostate cancer risk was observed with
increasing intakes of vitamin C-rich vegetables, including bell peppers and
broccoli. Fruit, other vegetables and vitamin A intakes did not appear to be strong
factors in the development of prostate cancer in this study.Prostate Cancer and
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Prostatic Diseases advance online publication, 22 May 2007;
doi:10.1038/sj.pcan.4500979.
Berquin IM, Min Y, Wu R, Wu J, Perry D, Cline JM, Thomas MJ, Thornburg T, Kulik G,
Smith A, Edwards IJ, D'Agostino R, Zhang H, Wu H, Kang JX, Chen YQ. (2007).
"Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids." jour.
clin. invest 117(7): 1866-1875.
lthough a causal role of genetic alterations in human cancer is well established, it
is still unclear whether dietary fat can modulate cancer risk in a predisposed
population. Epidemiological studies suggest that diets rich in omega-3
polyunsaturated fatty acids reduce cancer incidence. To determine the influence
of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we
used prostate-specific Pten-knockout mice, an immune-competent, orthotopic
prostate cancer model, and diets with defined polyunsaturated fatty acid levels.
We found that omega-3 fatty acids reduced prostate tumor growth, slowed
histopathological progression, and increased survival, whereas omega-6 fatty
acids had opposite effects. Introducing an omega-3 desaturase, which converts
omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor
growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had
lower proportions of phosphorylated Bad and higher apoptotic indexes compared
with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3induced cell death, and introduction of exogenous Bad restored the sensitivity to
omega-3 fatty acids. Our data suggest that modulation of prostate cancer
development by polyunsaturated fatty acids is mediated in part through Baddependent apoptosis. This study highlights the importance of gene-diet
interactions in prostate cancer.
Bostonnews.com. (2007, july-9). "Does Lycopene in tomatoes help prevent prostate
cancer?" from
http://www.boston.com/news/globe/health_science/articles/2007/07/09/does_the_lycope
ne_in_tomatoes_help_prevent_prostate_cancer/.
Centers for Disease Control. (2007). "2007 prostate data." from
http://www.cdc.gov/cancer/prostate/prospdf/0607_prostate_fs.pdf.
This PDF from the CDC has recent data on prostate cancer like risk factors- age,
race, and family history as well as prevention/risk- herbal supplements, good
diets(prevention), vitamin E, poor diets (risk), hormones, environment, obesity.
Also has screening info DRE, and PSA test.
Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J. (2007). "A Prospective
Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk." Cancer
Epidemiology And Biomarkers & prevention ahead of print.
BACKGROUND: Animal models suggest that n-3 fatty acids inhibit prostate
cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies
do not uniformly support these findings.METHODS: A nested case-control study
was conducted among 14,916 apparently healthy men who provided blood
Emerging Issues152
samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed
with prostate cancer during a 13-year follow-up and their matched controls.
Conditional logistic regression was used to estimate the relative risks (RR) and
95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and
Gleason < 7) and aggressive (stage C/D, Gleason >/= 7, subsequent distant
metastasis or death) prostate cancer associated with blood levels of specific fatty
acids expressed as percentages of total fatty acids.RESULTS: Whole blood
levels of all long-chain n-3 fatty acids examined and of linoleic acid were
inversely related to overall prostate cancer risk (RRQ5vs.Q1, 0.59; 95% CI, 0.380.93; Ptrend = 0.01 for total long-chain n-3 fatty acids and RRQ5vs.Q1, 0.62;
95% CI, 0.41-0.95; Ptrend = 0.03 for linoleic). Blood levels of gamma-linolenic
and dihomo-gamma-linolenic acids, fatty acids resulting from the metabolism of
linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI,
0.94-2.12; Ptrend = 0.05 for gamma-linolenic and RR, 1.54; 95% CI, 1.03-2.30;
Ptrend = 0.02 for dihomo-gamma-linolenic acid). Levels of arachidonic and
alpha-linolenic acids were unrelated to prostate cancer.CONCLUSIONS: Higher
blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of
linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated
with a reduced risk of prostate cancer. The direct associations of linoleic acid
metabolites with prostate cancer risk deserve further investigation. (Cancer
Epidemiol Biomarkers Prev 2007;16(7):OF1-7).
Demark-Wahnefried W, Clipp EC, Lipkus IM, Lobach D, Snyder DC, Sloane R,
Peterson B, Macri JM, Rock CL, McBride CM, Kraus WE. (2007). "Main outcomes of the
FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention
among breast and prostate cancer survivors." journal of clinical oncology 25(19): 27092718.
PURPOSE: Cancer survivors are at increased risk for cardiovascular disease,
diabetes, osteoporosis, and second primary tumors. Healthful lifestyle practices
may improve the health and well-being of survivors. The FRESH START trial
tested the efficacy of sequentially tailored versus standardized mailed materials
on improving cancer survivors' diet and exercise behaviors. METHODS: Five
hundred forty-three individuals with newly diagnosed locoregional breast or
prostate cancer were recruited from 39 states and two provinces within North
America. Participants were randomly assigned either to a 10-month program of
tailored mailed print materials promoting fruit and vegetable (F&V) consumption,
reducing total/saturated fat intake, and/or increasing exercise or to a 10-month
program of nontailored mailed materials on diet and exercise available in the
public domain. Telephone surveys conducted at baseline and 1 year assessed
body mass index (BMI), dietary consumption, physical activity, and other
psychosocial/behavioral indices. Clinical assessments were conducted on a 23%
subsample; information was used to validate self-reports. RESULTS: Five
hundred nineteen participants completed the 1-year follow-up (4.4% attrition;
sample characteristics: 57 +/- 10.8 years old, 83% white, 56% female, 64%
overweight/obese, and 0% underweight). Although both arms significantly
improved their lifestyle behaviors (P < .05), significantly greater gains occurred in
Emerging Issues153
the FRESH START intervention versus the control arm (practice of two or more
goal behaviors: +34% v +18%, P < .0001; exercise minutes per week: +59.3 v
+39.2 minutes, P = .02; F&V per day: +1.1 v +0.6 servings, P = .01; total fat: 4.4% v -2.1%, P < .0001; saturated fat: -1.3% v -0.3%, P < .0001; and BMI: -0.3 v
+0.1 kg/m2, respectively, P = .004). CONCLUSION: Mailed material
interventions, especially those that are tailored, are effective in promoting
healthful lifestyle changes among cancer survivors. Further study is needed to
determine sustainability, cost to benefit, and generalizability to other cancer
populations.
Eriksson M, Wedel H, Wallander MA, Krakau I, Hugosson J, Carlsson S, Svärdsudd K.
(2007). "The impact of birth weight on prostate cancer incidence and mortality in a
population-based study of men born in 1913 and followed up from 50 to 85 years of
age." prostate 67(11): 1247-54.
BACKGROUND: Insulin-like growth factor-I (IGF-I) hormone is directly
associated with birth weight (BW), and high IGF-I measured in adults is
associated with increased risk of prostate cancer (PCA). Whether BW and PCA
are related is inconclusive to date. METHODS: BW and PCA incidence and
mortality data for a population-based cohort of 1,436 singleton Swedish men
born in 1913 and followed until 85 years of age were obtained. RESULTS: BW
>/= 4,250 g was associated with significantly higher PCA incidence [62% (CI:
4%-151%)] and PCA mortality [82% (CI: 3%-221%)] than BW 3,001-4,249 g,
even when other potential effect modifiers were taken into account. The hazards
ratio for PCA incidence fell from approximately 3 at age 50 to unity at age 85.
Approximately one out of every six PCA incident cases between 50 and 70 years
of age could be attributed to BW >/= 4,250 g. CONCLUSIONS: In the current
study PCA incidence and mortality rate appears to increase with BW. Prostate
67: 1247-1254, 2007. (c) 2007 Wiley-Liss, Inc.
Gao X, LaValley MP, Tucker KL. (2005). "Prospective studies of dairy product and
calcium intakes and prostate cancer risk: a meta-analysis." Journal of the National
Cancer Institute 97(23): 1768-77.
BACKGROUND: The Dietary Guidelines for Americans 2005 recommends that
Americans increase their intake of dairy products. However, some studies have
reported that increasing dairy product intake is associated with an increased risk
of prostate cancer. We conducted a meta-analysis to examine associations
between intakes of calcium and dairy products and the risk of prostate cancer.
METHODS: We searched Medline for prospective studies published in Englishlanguage journals from 1966 through May 2005. We identified 12 publications
that used total, advanced, or fatal prostate cancer as end points and reported
associations as relative risks (RRs) with 95% confidence intervals (CIs) by
category of dairy product or calcium intake. Data were extracted using
standardized data forms. Random-effects models were used to pool study results
and to assess dose-response relationships between dairy product or calcium
intakes and the risk of prostate cancer. We conducted sensitivity analyses by
changing criteria for inclusion of studies or by using fixed-effects models. All
Emerging Issues154
statistical tests were two-sided. RESULTS: Men with the highest intake of dairy
products (RR =1.11 [95% CI = 1.00 to 1.22], P = .047) and calcium (RR = 1.39
[95% CI = 1.09 to 1.77], P = .018) were more likely to develop prostate cancer
than men with the lowest intake. Dose-response analyses suggested that dairy
product and calcium intakes were each positively associated with the risk of
prostate cancer (Ptrend = .029 and .014, respectively). Sensitivity analyses
generally supported these associations, although the statistical significance was
attenuated. The pooled relative risks of advanced prostate cancer were 1.33
(95% CI = 1.00 to 1.78; P = .055) for the highest versus lowest intake categories
of dairy products and 1.46 (95% CI = 0.65 to 3.25; P > .2) for the highest versus
lowest intake categories of calcium. CONCLUSIONS: High intake of dairy
products and calcium may be associated with an increased risk of prostate
cancer, although the increase appears to be small.
Giovannucci E, Liu Y, Stampfer MJ, Willett WC. (2006). "A prospective study of calcium
intake and incident and fatal prostate cancer." Cancer Epidemiology And Biomarkers &
prevention 15(2): 203-210.
Prostate cancer is the most common incident cancer and the second leading
cause of cancer mortality in U.S. males. Higher milk intake has been relatively
consistently associated with an increased risk of prostate cancer, especially
advanced prostate cancer. Some data suggest that high intake of calcium might
account for this association, but this relationship remains controversial. We
hypothesized that high calcium intake, possibly by lowering 1,25(OH)2 vitamin D
levels, is associated with poorer differentiation in prostate cancer and thereby
with fatal prostate cancer. We examined calcium intake in relation to prostate
cancer risk using data from the Health Professionals Follow-up Study, a
prospective cohort study of 47,750 male health professionals with no history of
cancer other than nonmelanoma skin cancer at baseline. We assessed total,
dietary, and supplementary calcium intake in 1986, 1990, 1994, and 1998, using
a validated food frequency questionnaire. We calculated the multivariable relative
risk (RR) and 95% confidence intervals (95% CI) using Cox proportional hazards
regression. Over 16 years of follow-up, we identified 3,544 total cases of prostate
cancer, 523 advanced (extraprostatic) cases, and 312 fatal cases. Higher
calcium intake was not appreciably associated with total or nonadvanced
prostate cancer but was associated with a higher risk of advanced and fatal
prostate cancer [for fatal prostate cancer, compared with men whose long-term
calcium intake was 500-749 mg/d (excluding supplement use of <5 years); those
with intakes of 1,500-1,999 mg/d had a RR, 1.87; 95% CI, 1.17-3.01; and those
with > or = 2,000 mg/d had a RR, 2.43; 95% CI, 1.32-4.48; P(trend) = 0.003].
Dietary calcium and supplementary calcium were independently associated with
an increased risk. For high-grade prostate cancer (Gleason > or = 7), an
association was observed for high versus low calcium intake (RR, 1.89; 95% CI,
1.32-2.71; P(trend) = 0.005), but a nonsignificant, inverse association was
observed for organ-confined, low-grade prostate cancer (RR, 0.79; 95% CI, 0.501.25; P(trend) = 0.09). In a sample of this cohort, higher calcium intake was
associated with lower circulating 1,25(OH)2 vitamin D levels. Our findings
Emerging Issues155
suggest that calcium intakes exceeding 1,500 mg/d may be associated with a
decrease in differentiation in prostate cancer and ultimately with a higher risk of
advanced and fatal prostate cancer but not with well-differentiated, organconfined cancers.
Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC.
(2006). "Prospective study of predictors of vitamin D status and cancer incidence and
mortality in men." Journal of the National Cancer Institute 98(7): 451-459.
BACKGROUND: Vitamin D has potent anticancer properties, especially against
digestive-system cancers. Many human studies have used geographic residence
as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we
considered multiple determinants of vitamin D exposure (dietary and
supplementary vitamin D, skin pigmentation, adiposity, geographic residence,
and leisure-time physical activity-to estimate sunlight exposure) in relation to
cancer risk in the Health Professionals Follow-Up Study. METHODS: Among
1095 men of this cohort, we quantified the relation of these six determinants to
plasma 25-hydroxy-vitamin D [25(OH)D] level by use of a multiple linear
regression model. We used results from the model to compute a predicted
25(OH)D level for each of 47,800 men in the cohort based on these
characteristics. We then prospectively examined this variable in relation to
cancer risk with multivariable Cox proportional hazards models. RESULTS: From
1986 through January 31, 2000, we documented 4286 incident cancers
(excluding organ-confined prostate cancer and nonmelanoma skin cancer) and
2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L
in predicted 25(OH)D level was associated with a 17% reduction in total cancer
incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI] =
0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI =
0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR =
0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758
per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000
men for the top decile; these respective rates were 326 per 100,000 and 277 per
100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for
digestive-system cancer mortality. Results were similar when we controlled
further for body mass index or physical activity level. CONCLUSIONS: Low levels
of vitamin D may be associated with increased cancer incidence and mortality in
men, particularly for digestive-system cancers. The vitamin D supplementation
necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500
IU/day.
Grant, WB. (2006). "Epidemiology of disease risks in relation to vitamin D insufficiency."
Progess in Biophysics and molecular biology 92(1): 65-79.
Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving
increased attention lately for its role in maintaining optimal health. Although the
calcemic effects of vitamin D have been known for about a century, the noncalcemic effects have been studied intently only during the past two-three
decades. The strongest links to the beneficial roles of UVB and vitamin D to date
Emerging Issues156
are for bone and muscle conditions and diseases. There is also a preponderance
of evidence from a variety of studies that vitamin D reduces the risk of colon
cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33
ng/mL (82 nmol/L) associated with a 50% lower incidence of colorectal cancer.
There is also reasonable evidence that vitamin D reduces the risk of breast, lung,
ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker,
primarily ecologic, evidence for the role of vitamin D in reducing the risk of an
additional dozen types of cancer. There is reasonably strong ecologic and casecontrol evidence that vitamin D reduces the risk of autoimmune diseases
including such as multiple sclerosis and type 1 diabetes mellitus, and weaker
evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus,
hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts
its effect are generally well understood for the various conditions and diseases
discussed here.
Hoption Cann SA, Qiu Z, van Netten C. (2007). "A Prospective Study of Iodine Status,
Thyroid Function, and Prostate Cancer Risk: Follow-up of the First National Health and
Nutrition Examination Survey." nutrition and cancer 58(1): 28-34.
Few studies have investigated the association between iodine status, thyroid
disease, and cancer risk despite evidence that thyroid function impacts many
organs, including the prostate. We investigated iodine status and prostate cancer
risk prospectively using data from the NHANES I Epidemiologic Follow-up Study.
Participants were stratified into tertiles according to the urinary iodine/creatinine
ratio, as a marker of iodine exposure. As iodine is an integral constituent of
thyroid hormones, we also examined the relationship between thyroid disease
and prostate cancer risk. Relative to the group with low urinary iodine, the ageadjusted hazard ratio was higher (although marginally insignificant) in the
moderate group, hazard ratio 1.33 (95% confidence interval 1.00-1.78), and
significantly lower in the high group, 0.71 (0.51-0.99). Thyroid disease was
associated with an increased prostate cancer risk, 2.34 (1.24-4.43). Similarly, >
10 yr since thyroid disease diagnosis was associated with an elevated risk, 3.38
(1.66-6.87). After adjusting for other confounding factors, only a history of thyroid
disease, 2.16 (1.13-4.14), and > 10 yr since diagnosis of thyroid disease, 3.17
(1.54-6.51) remained significant. Although the role of dietary iodine remains
speculative, a role for thyroid disease and/or factors contributing to thyroid
disease as a risk factor for prostate carcinogenesis warrants additional
investigation.
Kirsh VA, Hayes RB, Mayne ST, Chatterjee N, Subar AF, Dixon LB, Albanes D,
Andriole GL, Urban DA, Peters U (2006). "Supplemental and dietary vitamin E, betacarotene, and vitamin C intakes and prostate cancer risk." Journal of the National
Cancer Institute 98(4): 245-54.
BACKGROUND: Vitamin E, beta-carotene, and vitamin C are micronutrient
antioxidants that protect cells from oxidative damage involved in prostate
carcinogenesis. In separate trials, supplemental vitamin E was associated with a
decreased risk of prostate cancer among smokers and supplemental beta-
Emerging Issues157
carotene was associated with a decreased risk of prostate cancer among men
with low baseline plasma beta-carotene levels. METHODS: We evaluated the
association between intake of these micronutrient antioxidants from foods and
supplements and the risk of prostate cancer among men in the screening arm of
the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline,
trial participants completed a 137-item food frequency questionnaire that
included detailed questions on 12 individual supplements. Cox proportional
hazards models were used to estimate relative risks (RRs) and 95% confidence
intervals (CIs). All statistical tests were two-sided. RESULTS: We identified 1338
cases of prostate cancer among 29 361 men during up to 8 years of follow-up.
Overall, there was no association between prostate cancer risk and dietary or
supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among
current and recent (i.e., within the previous 10 years) smokers, decreasing risks
of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were
associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95%
CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use
versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin
E use. Supplemental beta-carotene intake at a dose level of at least 2000
microg/day was associated with decreased prostate cancer risk in men with low
(below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52,
95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced
prostate cancer was 492 per 100,000 person-years in those who did not take
supplemental vitamin E, 153 per 100,000 person-years in those who took more
than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in
those who took supplemental vitamin E for 10 or more years. Among men with
low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was
1122 per 100,000 person-years in those who did not take supplemental betacarotene, and 623 per 100,000 person-years in those who took at least 2000
microg/day of supplemental beta-carotene. CONCLUSIONS: Our results do not
provide strong support for population-wide implementation of high-dose
antioxidant supplementation for the prevention of prostate cancer. However,
vitamin E supplementation in male smokers and beta-carotene supplementation
in men with low dietary beta-carotene intakes were associated with reduced risk
of this disease.
Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA,
Crawford ED, Hayes RB. (2006). "A prospective study of lycopene and tomato product
intake and risk of prostate cancer." Cancer Epidemiology And Biomarkers & prevention
15(1): 92-98.
BACKGROUND: Dietary lycopene and tomato products may reduce risk of
prostate cancer; however, uncertainty remains about this possible
association.METHODS: We evaluated the association between intake of
lycopene and specific tomato products and prostate cancer risk in the Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study
designed to investigate cancer early detection methods and etiologic
determinants. Participants completed both a general risk factor and a 137-item
Emerging Issues158
food frequency questionnaire at baseline. A total of 1,338 cases of prostate
cancer were identified among 29,361 men during an average of 4.2 years of
follow-up.RESULTS: Lycopene intake was not associated with prostate cancer
risk. Reduced risks were also not found for total tomato servings or for most
tomato-based foods. Statistically nonsignificant inverse associations were noted
for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval
(95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06
and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and
spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95%
CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among
men with a family history of prostate cancer, risks were decreased in relation to
increased consumption of lycopene (P(trend)=0.04) and specific tomato-based
foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)=0.15;
lasagna, P(trend)=0.02).CONCLUSIONS: This large study does not support the
hypothesis that greater lycopene/tomato product consumption protects from
prostate cancer. Evidence for protective associations in subjects with a family
history of prostate cancer requires further corroboration. (Cancer Epidemiol
Biomarkers Prev 2006;15(1):92-8).
Negri E, Bertuccio P, Talamini R, Franceschi S, Montella M, Giacosa A, Pelucchi C, La
Vecchia C. (2006). "A history of cancer in the husband does not increase the risk of
breast cancer." International Journal of Cancer: 118(12): 3177-3179.
Spouses share the home environment, and dietary and other lifestyle habits.
Furthermore, a cancer diagnosis in the husband is a stressful event for the wife
also. Thus, a history of cancer in the husband may be an indicator of breast
cancer risk. We investigated the issue in a large Italian multicentric case-control
study on 2,588 women with incident breast cancer and 2,569 female hospital
controls, admitted for acute, non neoplastic diseases. The adjusted odds ratio
(OR) was 1.0 (95% confidence interval, CI, 0.7-1.4) for a history of any type of
cancer in the husband, 1.0 (95% 0.4-2.7) for stomach, 0.7 (95% 0.2-2.3) for
intestinal (chiefly colorectal), 0.9 (95% CI 0.5-1.7) for lung, and 1.3 (95% CI 0.44.3) for prostate cancer. The OR was close to unity also when data were
analyzed in separate strata of patient's or husband's age, patient's education, or
vital status of the husband. This study suggests that women whose husband had
a diagnosis of cancer are not at increased risk of breast cancer, although results
for individual cancer sites should be interpreted with caution, due to small
numbers.
Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King I, Thornquist M, Goodman
G. (2007). "(n-6) PUFA Increase and Dairy Foods Decrease Prostate Cancer Risk in
Heavy Smokers." Journal of Nutrition 137(7): 1821-1827.
Previous studies offer suggestive, but not definitive, evidence that total fat or
specific fats may increase prostate cancer risk. This study investigates
associations of dietary fat, meat, and dairy foods with prostate cancer risk among
12,025 men in the Carotene and Retinol Efficacy Trial (CARET). After 11 y of
follow-up, 890 incident prostate cancers were reported and confirmed. Diet was
Emerging Issues159
assessed by a biannual FFQ. Cox proportional hazards models were used to
estimate multivariate-adjusted hazard ratios (HR) of intake of fat and fat-related
foods (meat and dairy) with prostate cancer incidence. Multiplicative interaction
terms tested whether associations differed by family history, race, or smoking.
Overall, fat was not associated with total, nonaggressive or aggressive prostate
cancer. In subgroup analyses the HR for men with a family history of prostate
cancer were 2.47 (95%CI = 0.96-6.37) and 2.61 (95% CI = 1.01-6.72) for total
polyunsaturated fat (PUFA) and (n-6) PUFA for the 4th vs. 1st quartiles of intake,
respectively. Red meat was not associated with total or aggressive prostate
cancer. However, higher dairy intake had a statistically significant reduced risk of
aggressive prostate cancer than lower dairy intake (HR = 0.59, 95% CI = 0.400.85). Dairy foods also protected current, but not former, smokers against
aggressive cancer (HR = 0.42, 95% CI = 0.25-0.70). Our findings suggest that
associations of dietary fat with prostate cancer risk may vary by type of fat or fatcontaining food, and that risk may vary by host factors, including family history
and smoking.
Stroup SP, Cullen J, Auge BK, L'esperance JO, Kang SK (2007). "Effect of obesity on
prostate-specific antigen recurrence after radiation therapy for localized prostate cancer
as measured by the 2006 Radiation Therapy Oncology Group-American Society for
Therapeutic Radiation and Oncology (RTOG-ASTRO) Phoenix consensus definition."
Cancer PMID: 17614338 [PubMed - as supplied by publisher]: Hasnt been printed
yet.
BACKGROUND.: Given the limited data regarding the impact of obesity on
treatment outcomes after external beam radiation therapy (EBRT) for the
definitive treatment of prostate cancer, the authors sought to evaluate the effect
of obesity as measured by body mass index (BMI) on biochemical disease
recurrence (BCR) using the most current 2006 Radiation Therapy Oncology
Group-American Society for Therapeutic Radiation and Oncology (RTOGASTRO) Phoenix consensus definition (prostate-specific antigen [PSA] nadir + 2
ng/mL). METHODS.: A retrospective cohort study identified men who underwent
primary EBRT for localized prostate cancer between 1989 and 2003 using the
Center for Prostate Disease Research (CPDR) Multi-center National Database.
BMI was calculated (in kg/m(2)) and the data were analyzed. Univariate and
multivariate Cox proportional hazards regression analyses were used to
determine whether BMI significantly predicted BCR. RESULTS.: Of the 1868
eligible patients, 399 (21%) were obese. The median age of the patients and
pretreatment PSA level were 70.2 years and 8.2 ng/mL, respectively. Of 1320
patients for whom data were available with which to calculate PSA recurrence
(PSA nadir + 2 ng/mL), a total of 554 men (42.0%) experienced BCR. On
univariate analysis, BMI was found to be an independent predictor of PSA
recurrence (P = .02), as was race, pretreatment PSA level, EBRT dose, clinical T
classification, Gleason score, PSA nadir, and the use of androgen-deprivation
therapy (ADT). On multivariate analysis, BMI remained a significant predictor of
BCR (P = .008). CONCLUSIONS.: To the authors' knowledge, this is the first
study to report the association between obesity and BCR after EBRT for
Emerging Issues160
localized prostate cancer as measured by the updated 2006 RTOG-ASTRO
definition. A higher BMI is associated with greater odds of BCR after undergoing
definitive EBRT. Cancer 2007. Published 2007 by the American Cancer Society.
Sun M, Ma L. (2006). "Treatments of exceptionally large prostate cancer patients with
low-energy intensity-modulated photons." journal of applied clinical medical physics
7(4): 43-9.
An inverse planning technique was developed for large-sized prostate cancer
patients treatments using 6-MV intensity modulated photon beams. Comparisons
of the treatment plans between using 6-MV and 18-MV intensity modulated
beams were carried out for a cohort of ten patient cases. The dependence of the
plan quality on the beam energies was analyzed for these cases. We found that
6-MV produced equivalent plans as 18-MV for both targets and critical structures
such as the rectum and the bladder. The differences in the integral dose and the
mean dose to the normal tissue surrounding the target between 6- and 18-MV
plans were found to be small in contrast to 3D conformal plans. This shows that
the low entrance dose of the high energy photon beams is mostly compensated
by the high exit dose for even exceptionally large-size patients. In conclusion, 6MV intensity modulated beam is a feasible choice for treating large-sized
prostate cancer patients provided proper inverse planning techniques are
adopted.
Szkudelska K, Nogowski L. (2007). "Genistein-A dietary compound inducing hormonal
and metabolic changes." Journal of Steroid biochemical molecular biology ahead of
pring.
Genistein is a plant-derived compound possessing well-known preventive activity
in breast and prostate cancer, cardiovascular diseases and post-menopausal
problems. Lately, the interests in genistein have widened. The studies
concerning effects of genistein performed on animals and humans revealed other
aspects of its action - the metabolic alterations at the cellular level and in the
whole organism. It was shown that genistein decreased body and fat tissue
weight gains accompanied by reduced food intake. After ingestion of dietary
genistein, the alterations in concentrations of hormones such as: insulin, leptin,
thyroid hormones, adrenocorticotropic hormone, cortisol and corticosterone were
observed. The changes in lipid parameters - triglycerides and cholesterol were
also noticed as a consequence of genistein administration. Moreover, the altered
expression of genes engaged in lipid metabolism, disturbed glucose transport
into cells, affected lipolysis and lipogenesis and changed ATP synthesis were
found as a result of genistein action.
Weinstein SJ, Wright ME, Lawson KA, Snyder K, Männistö S, Taylor PR, Virtamo J,
Albanes D. (2007). "Serum and dietary vitamin E in relation to prostate cancer risk."
Cancer Epidemiology And Biomarkers & prevention 16(6): 1253-9.
Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate
cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer
Prevention Study. We investigated whether serum alpha-tocopherol or intake of
Emerging Issues161
vitamin E (eight tocopherols and tocotrienols) was associated with prostate
cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, betaCarotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers,
ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident
prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was
measured by high-performance liquid chromatography and the components of
vitamin E intake were estimated based on a 276-item food frequency
questionnaire and food chemistry analyses. Proportional hazard models were
used to determine multivariate-adjusted relative risks (RR) and 95% confidence
intervals (95% CI). Higher serum alpha-tocopherol was associated with reduced
risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest
quintile; Ptrend = 0.03) and was strongly and inversely related to the risk of
developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; Ptrend = 0.002).
The inverse serum alpha-tocopherol-prostate cancer association was greater
among those who were supplemented with either alpha-tocopherol or betacarotene during the trial. There were no associations between prostate cancer
and the individual dietary tocopherols and tocotrienols. In summary, higher
prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin
E, was associated with lower risk of developing prostate cancer, particularly
advanced prostate cancer.
Werny DM, Thompson T, Saraiya M, Freedman D, Kottiri BJ, German RR, Wener M.
(2007). "Obesity is negatively associated with prostate-specific antigen in U.S. men,
2001-2004." Cancer Epidemiology And Biomarkers & prevention 16(1): 70-76.
ACKGROUND: Recent studies have shown a negative association between body
mass index (BMI) and prostate-specific antigen (PSA), a commonly used serum
marker for the detection and diagnosis of prostate cancer. We have examined
the association between several anthropometric measures and PSA in a
nationally representative sample of men. METHODS: We analyzed data from the
2001-2004 National Health and Nutrition Examination Survey. Participants in this
study were men ages >or=40 years without previously diagnosed prostate cancer
who had PSA measured. Height, weight, waist circumference, BMI, triceps
skinfold, subscapular skinfold, and calculated total body water were examined
categorically by quintiles using multiple linear regression models. All tests of
significance were two sided. RESULTS: Among white men, we report a trend for
decreasing PSA with increasing weight, BMI, waist circumference, triceps
skinfold thickness, and calculated total body water. Among Mexican American
men, we found a trend for decreasing PSA with increasing BMI, and among black
men we found a trend for decreasing PSA with increasing triceps thickness.
None of the interaction terms between race/ethnicity and any of the
anthropometric measures were statistically significant. Controlling for age and
race/ethnicity in the multiple linear regression model, we found moderate
declines in PSA with a 1 SD increase in BMI [5.9% decrease (95% confidence
interval, -9.0% to -2.8%) in geometric mean PSA per 5.2-unit increase], weight
[5.9% decline (-8.8% to -2.8%) per 17.7-kg increase], waist circumference [6.6%
decline (-9.4% to -3.6%) per 13.4-cm increase], triceps skinfold [5.4% decline (-
Emerging Issues162
8.9% to -1.8%) per 6.4-mm increase], and calculated total body water [5.7%
decline (-8.9% to -2.4%) per 6.5-liter increase]. CONCLUSION: Our populationbased, nationally representative results expand the validity of previous studies on
obesity and PSA. Higher weight, BMI, waist circumference, triceps skinfold, and
total body water are associated with moderately lower PSA values. A prospective
study is needed to verify whether this association affects the accuracy of the PSA
test in obese men.
Wicht A, Hamza A, Loertzer H, Dietl M, Heynemann H, Fornara P. (2006). "[Diagnostics
and treatment of prostate cancer after kidney transplantation]." Urologe A. 45(1): 32-37.
The number of patients with prostate cancer and end-stage renal disease or
prostate cancer following kidney transplantation has continuously increased in
industrialized countries. According to the data generated by Penn et al. a higher
incidence of prostate cancer following kidney transplantation can be seen but is
probably due to a more intense screening of the recipients. It is rather a common
opinion that no elevated risk of prostate cancer following kidney transplantation
exists.In patients with strictly localized prostate cancer curative treatment should
be the aim also after kidney transplantation. Kidney transplantation does not
interfere with surgical access to the prostate gland (retropubic or perineal).
Nonlocal tumors of the prostate should also be treated following the general
recommendations regarding prostate cancer. Looking at the current literature, a
reduction or change of immunosuppression seems reasonable. It is necessary to
establish a nationwide (or even European) cancer register, especially for patients
before and after transplantation.
Emerging Issues163
Personal Care Products
Andrew, A. S., A. R. Schned, et al. (2004). "Bladder cancer risk and personal hair dye
use." Int J Cancer 109(4): 581-6.
Several cohort and case-control studies have found an increased risk of bladder
cancer among hairdressers and barbers who are occupationally exposed to hair
dyes. However, the carcinogenic risk associated with personal use of hair dyes
remains uncertain since several large case-control and cohort studies did not find
an association between personal hair dye use and bladder cancer. To address
this question, the authors used data collected on 459 bladder cancer cases and
665 controls who were interviewed as part of a case-control study conducted in
New Hampshire between 1994 and 1998. Participants underwent a structured
personal interview with regard to history of hair dye use and bladder cancer risk
factors. Unconditional logistic regression analysis was used to compute odds
ratios that were associated with hair dye use, while controlling for potential
confounding factors. A history of any hair dye use was inversely associated with
bladder cancer incidence in men [adjusted odds ratio (OR) = 0.5; 95%
confidence interval (CI)=0.3-0.8], although risk reductions were not statistically
significant for individual dye types. In women, use of permanent (adjusted OR =
1.5; 95%CI = 0.8-2.7) and rinse-type hair dye (adjusted OR = 1.7; 95%CI = 0.83.6) were associated with a modestly elevated risk of bladder cancer but with
limited statistical precision; no association was found with use of semi-permanent
dyes (adjusted OR = 0.7; 95%CI = 0.3-1.4). For permanent hair dye use, odds
ratios were most pronounced for younger age at first use, higher frequency and
prolonged time since first use; however there were no clear trends in risk by
these factors. In light of the prevalence of hair dye use, further studies are
needed that address the effects of specific colors and types of hair dyes along
with the possible role of individual susceptibility.
Donovan, M., C. M. Tiwary, D. Axelrod, A. J. Sasco, L. Jones, R. Hajek, E. Sauber, J.
Kuo and D. L. Davis (2007). "Personal care products that contain estrogens or
xenoestrogens may increase breast cancer risk." Med Hypotheses 68(4): 756-66.
Established models of breast cancer risk, such as the Gail model, do not account
for patterns of the disease in women under the age of 35, especially in African
Americans. With the possible exceptions of ionizing radiation or inheriting a
known genetic mutation, most of the known risk factors for breast cancer are
related to cumulative lifetime exposure to estrogens. Increased risk of breast
cancer has been associated with earlier onset of menses or later age at
menopause, nulliparity or late first parity, use of hormonal contraceptives or
hormone replacement therapy, shorter lactation history, exposure to light at night,
obesity, and regular ingestion of alcohol, all of which increase circulating levels of
unbound estradiol. Among African Americans at all ages, use of hormonecontaining personal care products (PCPs) is more common than among whites,
as is premature appearance of secondary sexual characteristics among infants
and toddlers. We hypothesize that the use of estrogen and other hormone-
Emerging Issues164
containing PCPs in young African American women accounts, in part, for their
increased risk of breast cancer prior to menopause, by subjecting breast buds to
elevated estrogen exposure during critical windows of vulnerability in utero and in
early life. These early life and continuing exposures to estrogenic and
xenoestrogenic agents may also contribute to the increased lethality of breast
cancer in young women in general and in African American women of all ages.
Public disclosure by manufacturers of proprietary hormonally active ingredients is
required for this research to move forward.
Exley, C., L. M. Charles, L. Barr, C. Martin, A. Polwart and P. D. Darbre (2007).
"Aluminium in human breast tissue." J Inorg Biochem.
Aluminium is omnipresent in everyday life and increased exposure is resulting in
a burgeoning body burden of this non-essential metal. Personal care products
are potential contributors to the body burden of aluminium and recent evidence
has linked breast cancer with aluminium-based antiperspirants. We have used
graphite furnace atomic absorption spectrometry (GFAAS) to measure the
aluminium content in breast biopsies obtained following mastectomies. The
aluminium content of breast tissue and breast tissue fat were in the range 4437nmol/g dry wt. and 3-192nmol/g oil, respectively. The aluminium content of
breast tissue in the outer regions (axilla and lateral) was significantly higher
(P=0.033) than the inner regions (middle and medial) of the breast. Whether
differences in the regional distribution of aluminium in the breast are related to
the known higher incidence of tumours in the outer upper quadrant of the breast
remains to be ascertained.
Karagas, Margaret R., Virginia A. Stannard, Leila A. Mott, Mary Jo Slattery, Steven K.
Spencer and Martin A. Weinstock (2002). "Use of Tanning Devices and Risk of Basal
Cell and Squamous Cell Skin Cancers." J. Natl. Cancer Inst. 94(3): 224-226.
Use of artificial tanning devices that emit UV radiation, such as tanning lamps
and tanning beds, has become increasingly popular in the United States.
Although an excess risk of nonmelanoma skin cancers might be predicted from
this exposure, little epidemiologic data exist. We conducted a population-based,
case-control study that included 603 basal cell carcinoma (BCC) case patients,
293 squamous cell carcinoma (SCC) case patients, and 540 control subjects.
Study participants were interviewed in person to obtain information on tanning
device use, sun exposure history, sun sensitivity, and other risk factors for skin
cancer. Overall, any use of tanning devices was associated with odds ratios of
2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to
2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure
did not affect our results. Our findings suggest that the use of tanning devices
may contribute to the incidence of nonmelanoma skin cancers. They highlight the
need to further evaluate the potential risks of BCC and SCC that are associated
with tanning lamp exposure and the appropriate public health response.
Emerging Issues165
Kleinsasser, N. H., E. R. Kastenbauer, et al. (2000). "Phthalates demonstrate
genotoxicity on human mucosa of the upper aerodigestive tract." Environmental and
Molecular Mutagenesis 35(1): 9-12.
Various phthalate compounds are used as softeners and plasticizers in a wide
range of plastic materials. There has been a growing concern regarding a
possible health hazard to humans. The mucosa of the upper aerodigestive tract
is the organ of first contact for the majority of xenobiotics, such as phthalates,
entering the body. Still, there is a lack of information concerning possible
carcinogenicity of phthalates in the upper aerodigestive tract. This motivated us
to investigate their genotoxic effects on human epithelia: human mucosal cells
derived from biopsies harvested during surgery of the oropharynx and the inferior
nasal turbinate, respectively. The alkaline version of the microgel electrophoresis
assay was used to detect single-strand breaks in the DNA following incubation
with dibutylphthalate (DBP) and diisobutylphthalate (DiBP). DNA damage was
induced by both DBP and DiBP in oropharyngeal and nasal mucosa, though the
effect of DiBP was more pronounced than that of DBP. Nasal mucosa proved to
be more sensitive than oropharyngeal epithelia. The results demonstrate
genotoxic effects of phthalates on human mucosal cells of the upper
aerodigestive tract, in contrast to earlier findings in animal models. Environ. Mol.
Mutagen. 35:9-12, 2000 © 2000 Wiley-Liss, Inc.
Emerging Issues166
Van Landingham, C. B., G. A. Lawrence and A. M. Shipp (2004). "Estimates of lifetimeabsorbed daily doses from the use of personal-care products containing
polyacrylamide: a Monte Carlo analysis." Risk Anal 24(3): 603-19.
Estimates of the lifetime-absorbed daily dose (LADD) of acrylamide resulting
from use of representative personal-care products containing polyacrylamides
have been developed. All of the parameters that determine the amount of
acrylamide absorbed by an individual vary from one individual to another.
Moreover, for some parameters there is uncertainty as to which is the correct or
representative value from a range of values. Consequently, the parameters used
in the estimation of the LADD of acrylamide from usage of a particular product
type (e.g., deodorant, makeup, etc.) were represented by distributions evaluated
using Monte Carlo analyses.((1-4)) From these data, distributions of values for
key parameters, such as the amount of acrylamide in polyacrylamide, absorption
fraction, etc., were defined and used to provide a distribution of LADDs for each
personal-care product. The estimated total acrylamide LADD (across all
products) for males and females at the median, mean, and 95th percentile of the
distribution of individual LADD values were 4.7 x 10(-8), 2.3 x 10(-7), and 7.3 x
10(-7) mg/kg/day for females and 3.6 x 10(-8), 1.7 x 10(-7), and 5.4 x 10(-7)
mg/kg/day for males. The ratio of the LADDs to risk-specific dose corresponding
to a target risk level of 1 x 10(-5), the acceptable risk level for this investigation,
derived using approaches typically used by the FDA, the USEPA, and proposed
for use by the European Union (EU) were also calculated. All ratios were well
below 1, indicating that all the extra lifetime cancer risk from the use of
polyacrylamide-containing personal-care products, in the manner assumed in this
assessment, are well below acceptable levels. Even if it were assumed that an
individual used all of the products together, the estimated LADD would still
provide a dose that was well below the acceptable risk levels.
Wierik, E. J., P. T. Hendricks and M. Boerstoel-Streefland (2004). "Clinical background
of women prescribed tibolone or combined estrogen + progestogen therapies: a UK
MediPlus study." Climacteric 7(2): 197-209.
OBJECTIVES: To describe and compare the history and clinical characteristics
of women who were prescribed tibolone or one of the following combined
estrogen + progestogen therapies (CEPT): sequential conjugated equine
estrogens (CEE)/norgestrel, sequential CEE/medroxyprogesterone acetate
(MPA), continuous CEE/MPA or continuous estradiol/norethisterone acetate
(NETA). METHODS: This was a descriptive study using MediPlus, a UK Primary
Care database; 3762 women participated who, between July 1st, 1999 and June
30th, 2001, were prescribed either tibolone or one of the CEPT regimens
mentioned above. Risk factors associated with endometrial cancer and breast
cancer were assessed. RESULTS: The results of this study suggest that the
clinical background of women who were prescribed tibolone differed from that of
the women who were prescribed the combination products. More frequently than
expected women who were most recently prescribed tibolone have a history of
chronic breast disease, a personal history of breast cancer or a history of being
prescribed (long-term) estrogen-only therapy. Furthermore, this group of women
Emerging Issues167
more frequently had hypertension and performed uterine procedures recorded in
their medical records. This preferential prescribing of tibolone occurs at first-ever
prescription of hormone therapy but is, in some instances, the underlying reason
for switch behavior. CONCLUSION: In the UK, general practitioners seem to
preferentially prescribe tibolone to women with an increased risk for breast and
endometrial cancer, as compared to women being prescribed other CEPT
products.
Emerging Issues168
SECTION B: PREVENTION AND EARLY DETECTION
Emerging Issues169
Healthcare Access
Abenhaim, H. A., L. Titus-Ernstoff and D. W. Cramer (2007). "Ovarian cancer risk in
relation to medical visits, pelvic examinations and type of health care provider." Cmaj
176(7): 941-7.
BACKGROUND: Whether the current recommendations for ovarian cancer
prevention and screening (annual history and physical examination) are effective
has not been evaluated. We examined the relation between health care use and
the risk of ovarian cancer. METHODS: Using a case-control study design, we
recorded the frequency of medical visits and pelvic examinations and the type of
health care provider visited during a 5-year period from interviews with women
with and without ovarian cancer between between July 1998 and July 2003. We
used multivariable logistic regression analysis to calculate the adjusted odds ratio
of ovarian cancer associated with the frequency of medical visits and pelvic
examinations and the type of health care provider. In addition, we stratified cases
and controls by menopausal status and cancer histologic subtype and grade.
RESULTS: A total of 668 cases and 721 age-matched controls agreed to
participate in the study. We observed an increased risk of ovarian cancer among
women who, during the 5-year study period, did not have a medical visit (odds
ratio [OR] 2.8, 95% confidence interval [CI] 1.5-5.0) or pelvic examination (OR
3.9, 95% CI 2.2-6.9) or who had no regular health care provider (OR 2.7, 95% CI
1.3-5.7). This increase in risk was most pronounced among women who were
postmenopausal (no medical visit, OR 7.7, 95% CI 2.6-23.0; no pelvic
examination, OR 3.3, 95% CI 1.7-6.0; no health care provider, OR 12.5, 95% CI
2.7-57.5). INTERPRETATION: Although the exact mechanism underlying the
association between medical visits, pelvic examinations and type of health care
provider and ovarian cancer is unknown, women should be encouraged to
maintain regular medical care.
Bradley CJ, Given CW, Dahman B, Luo Z, Virnig BA. (2007- May). "Diagnosis of
advanced cancer among elderly Medicare and Medicaid patients." Medical Care 45(5):
410-419.
BACKGROUND: Medicaid is implicated in late-stage cancer diagnoses, which is
the primary indicator of a poor prognosis. OBJECTIVE: We examined Medicaid
enrollment and cancer diagnosis in patients ages 66 years and older. Medicaid
enrollment was defined as enrolled 12+ months before diagnosis, enrolled <12
months before diagnosis, and enrolled after diagnosis. SUBJECTS: Medicaid
and Medicare administrative data were merged with the Michigan Tumor Registry
to extract a sample of 46,109 patients with a first primary diagnosis of prostate,
lung, breast, or colorectal cancer between 1997 and 2000. Measures were: (1)
diagnosed during the same month as death; (2) invasive, but unknown stage;
and (3) regional or distant stage disease. RESULTS:: Patients enrolled in
Medicaid <12 months before diagnosis were at greater risk of breast (odds ratio
[OR] = 2.70; 95% confidence interval [95% CI] = 1.22-5.99) and lung (OR = 2.18;
95% CI = 1.45-3.29) cancer diagnosis in the month of death than Medicare only
Emerging Issues170
patients. Similarly, patients with a history of Medicaid enrollment had a high risk
of diagnosis with invasive, but unknown breast, lung, and prostate cancer stage.
Patients enrolled in Medicaid following diagnosis had a higher risk of late stage
colorectal (OR = 1.30; 95% CI = 1.01-1.67), breast (OR = 2.12; 95% CI = 1.602.82), and lung (OR = 1.33; 95% CI = 1.02-1.75) cancer relative to Medicare only
patients. CONCLUSIONS: There is a preponderance of cancer diagnosis at
death and cancer diagnosis with invasive but unknown stage in the Medicaid
population, but the appropriateness of these diagnoses is unclear. Late-stage
cancer tends to precipitate Medicaid enrollment.
Carney, Patricia A., Joyce P. Yi, Linn A. Abraham, Diana L. Miglioretti, Erin J. Aiello,
Martha S. Gerrity, Lisa Reisch, Eric A. Berns, Edward A. Sickles and Joann G. Elmore
(2007). "Reactions to Uncertainty and the Accuracy of Diagnostic Mammography."
JGIM: Journal of General Internal Medicine 22(2): 234-241.
BACKGROUND: Reactions to uncertainty in clinical medicine can affect decision
making. OBJECTIVE: To assess the extent to which radiologists' reactions to
uncertainty influence diagnostic mammography interpretation. DESIGN: Crosssectional responses to a mailed survey assessed reactions to uncertainty using a
well-validated instrument. Responses were linked to radiologists' diagnostic
mammography interpretive performance obtained from three regional
mammography registries. PARTICIPANTS: One hundred thirty-two radiologists
from New Hampshire, Colorado, and Washington. MEASUREMENT: Mean
scores and either standard errors or confidence intervals were used to assess
physicians' reactions to uncertainty. Multivariable logistic regression models were
fit via generalized estimating equations to assess the impact of uncertainty on
diagnostic mammography interpretive performance while adjusting for potential
confounders. RESULTS: When examining radiologists' interpretation of additional
diagnostic mammograms (those after screening mammograms that detected
abnormalities), a 5-point increase in the reactions to uncertainty score was
associated with a 17% higher odds of having a positive mammogram given
cancer was diagnosed during follow-up (sensitivity), a 6% lower odds of a
negative mammogram given no cancer (specificity), a 4% lower odds (not
significant) of a cancer diagnosis given a positive mammogram (positive
predictive value [PPV]), and a 5% higher odds of having a positive mammogram
(abnormal interpretation). CONCLUSION: Mammograms interpreted by
radiologists who have more discomfort with uncertainty have higher likelihood of
being recalled.
Crew, K. D., A. I. Neugut, X. Wang, J. S. Jacobson, V. R. Grann, G. Raptis and D. L.
Hershman (2007). "Racial disparities in treatment and survival of male breast cancer." J
Clin Oncol 25(9): 1089-98.
PURPOSE: Black women with breast cancer have poorer survival than do white
women, but little is known about racial disparities in male breast cancer. We
analyzed race and other predictors of treatment and survival among men with
stage I-III breast cancer. PATIENTS AND METHODS: We used the Surveillance,
Epidemiology, and End Results (SEER) Medicare database to identify men 65
Emerging Issues171
years of age or older diagnosed with stage I-III breast cancer from 1991 to 2002.
Multivariate regression was used to compare those treated with those not treated
with either chemotherapy or radiation therapy, adjusting for known clinical and
demographic factors. Cox proportional hazards regression models were used to
analyze survival. RESULTS: Of 510 male breast cancer cases (456 white, 34
black), 94% underwent mastectomy, 28% received adjuvant chemotherapy, and
29% received radiation therapy. Among those with known hormone receptors,
95% had hormone-sensitive tumors. In a multivariate analysis, chemotherapy
was associated with younger age, advanced stage, and hormone receptornegative tumors. Radiation therapy was associated with younger age and
advanced stage. Black men were approximately 50% less likely to undergo
consultation with an oncologist and subsequently receive chemotherapy;
however, the results did not reach statistical significance. The breast cancerspecific mortality hazard ratio was more than tripled for black versus white men
(hazard ratio = 3.29; 95% CI, 1.10 to 9.86). CONCLUSION: After adjustment for
known clinical, demographic, and treatment factors, there was an association of
black race with increased male breast cancer-specific mortality. Although male
breast cancer is rare, the reasons for these disparities need to be better
understood.
Dietrich, A. J., J. N. Tobin, A. Cassells, C. M. Robinson, M. A. Greene, C. H. Sox, M. L.
Beach, K. N. DuHamel and R. G. Younge (2006). "Telephone care management to
improve cancer screening among low-income women: a randomized, controlled trial."
Ann Intern Med 144(8): 563-71.
BACKGROUND: Minority and low-income women receive fewer cancer
screenings than other women. OBJECTIVE: To evaluate the effect of a
telephone support intervention to increase rates of breast, cervical, and
colorectal cancer screening among minority and low-income women. DESIGN:
Randomized, controlled trial conducted between November 2001 and April 2004.
SETTING: 11 community and migrant health centers in New York City.
PATIENTS: 1413 women who were overdue for cancer screening.
INTERVENTION: Over 18 months, women assigned to the intervention group
received an average of 4 calls from prevention care managers and women
assigned to the control group received usual care. Follow-up data were available
for 99% of women, and 91% of the intervention group received at least 1 call.
MEASUREMENTS: Medical record documentation of mammography,
Papanicolaou testing, and colorectal cancer screening according to U.S.
Preventive Services Task Force recommendations. RESULTS: The proportion of
women who had mammography increased from 0.58 to 0.68 with the intervention
and decreased from 0.60 to 0.58 with usual care; the proportion who had
Papanicolaou testing increased from 0.71 to 0.78 with the intervention and was
unchanged with usual care; and the proportion who had colorectal screening
increased from 0.39 to 0.63 with the intervention and from 0.39 to 0.50 with usual
care. The difference in the change in screening rates between groups was 0.12
for mammography (95% CI, 0.06 to 0.19), 0.07 for Papanicolaou testing (CI, 0.01
to 0.12), and 0.13 for colorectal screening (CI, 0.07 to 0.19). The proportion of
Emerging Issues172
women who were up to date for 3 tests increased from 0.21 to 0.43 with the
intervention. LIMITATIONS: Participants were from 1 city and had access to a
regular source of care. Medical records may not have captured all cancer
screenings. CONCLUSIONS: Telephone support can improve cancer screening
rates among women who visit community and migrant health centers. The
intervention seems to be well suited to health plans, large medical groups, and
other organizations that seek to increase cancer screening rates and to address
disparities in care.
Elmore, J. G., S. H. Taplin, W. E. Barlow, G. R. Cutter, C. J. D'Orsi, R. E. Hendrick, L.
A. Abraham, J. S. Fosse and P. A. Carney (2005). "Does litigation influence medical
practice? The influence of community radiologists' medical malpractice perceptions and
experience on screening mammography." Radiology 236(1): 37-46.
PURPOSE: To assess the relationship between radiologists' perception of and
experience with medical malpractice and their patient-recall rates in actual
community-based clinical settings. MATERIALS AND METHODS: All study
activities were approved by the institutional review boards of the involved
institutions, and patient and radiologist informed consent was obtained where
necessary. This study was performed in three regions of the United States
(Washington, Colorado, and New Hampshire). Radiologists who routinely
interpret mammograms completed a mailed survey that included questions on
demographic data, practice environment, and medical malpractice. Survey
responses were linked to interpretive performance for all screening
mammography examinations performed between January 1, 1996, and
December 31, 2001. The odds of recall were modeled by using logistic
regression analysis based on generalized estimating equations that adjust for
study region. RESULTS: Of 181 eligible radiologists, 139 (76.8%) returned the
survey with full consent. The analysis included 124 radiologists who had
interpreted a total of 557 143 screening mammograms. Approximately half (64 of
122 [52.4%]) of the radiologists reported a prior malpractice claim, with 18
(14.8%) reporting mammography-related claims. The majority (n = 51 [81.0%]) of
the 63 radiologists who responded to a question regarding the degree of stress
caused by a medical malpractice claim described the experience as very or
extremely stressful. More than three of every four radiologists (ie, 94 [76.4%] of
123) expressed concern about the impact medical malpractice has on
mammography practice, with over half (72 [58.5%] of 123) indicating that their
concern moderately to greatly increased the number of their recommendations
for breast biopsies. Radiologists' estimates of their future malpractice risk were
substantially higher than the actual historical risk. Almost one of every three
radiologists (43 of 122 [35.3%]) had considered withdrawing from mammogram
interpretation because of malpractice concerns. No significant association was
found between recall rates and radiologists' experiences or perceptions of
medical malpractice. CONCLUSION: U.S. radiologists are extremely concerned
about medical malpractice and report that this concern affects their recall rates
and biopsy recommendations. However, medical malpractice experience and
concerns were not associated with recall or false-positive rates. Heightened
Emerging Issues173
concern of almost all radiologists may be a key reason that recall rates are higher
in the United States than in other countries, but this hypothesis requires further
study.
Fung-Kee-Fung, M., M. Brouwers, T. K. Oliver and B. Rosen (2007). "Health care use
and risk of ovarian cancer: is there a link?" Cmaj 176(7): 949-50.
Gee, G. C., A. Ryan, D. J. Laflamme and J. Holt (2006). "Self-reported discrimination
and mental health status among African descendants, Mexican Americans, and other
Latinos in the New Hampshire REACH 2010 Initiative: the added dimension of
immigration." Am J Public Health 96(10): 1821-8.
OBJECTIVES: We examined whether self-reported racial discrimination was
associated with mental health status and whether this association varied with
race/ethnicity or immigration status. METHODS: We performed secondary
analysis of a community intervention conducted in 2002 and 2003 for the New
Hampshire Racial and Ethnic Approaches to Community Health 2010 Initiative,
surveying African descendants, Mexican Americans, and other Latinos. We
assessed mental health status with the Mental Component Summary (MCS12) of
the Medical Outcomes Study Short Form 12, and measured discrimination with
questions related to respondents' ability to achieve goals, discomfort/anger at
treatment by others, and access to quality health care. RESULTS: Self-reported
discrimination was associated with a lower MCS12 score. Additionally, the
strength of the association between self-reported health care discrimination and
lower MCS12 score was strongest for African descendants, then Mexican
Americans, then other Latinos. These patterns may be explained by differences
in how long a respondent has lived in the United States. Furthermore, the
association of health care discrimination with lower MCS12 was weaker for
recent immigrants. CONCLUSIONS: Discrimination may be an important
predictor of poor mental health status among Black and Latino immigrants.
Previous findings of decreasing mental health status as immigrants acculturate
might partly be related to experiences with racial discrimination.
Harper, Diane M., Megan M. Moncur, William H. Harper, Gregory C. Burke, Cynthia A.
Rasmussen and Margaret C. Mumford (2000). "The Technical Performance and Clinical
Feasibility of Telecolposcopy." Journal of Family Practice 49(7): 623-627.
BACKGROUND: The purpose of our study was to demonstrate the technical
performance and clinical feasibility of a telecolposcopic system through
assessment of image transmission veracity, ease of office system
implementation, and the patient's acceptance of the electronic image
transmission. METHODS: We used a telecolposcopic system incorporating a
custom software package that integrated patient history, current gynecologic
status, epidemiologic risk factors, and colposcopic images for local medical
documentation and transmission. Satisfaction questionnaires were developed to
measure ease of implementation at the remote sites and the patients' acceptance
of telecolposcopy. RESULTS: Seventy-nine women participated in our trial. From
3 to 20 images were captured for each woman, documenting cervical squamous
Emerging Issues174
intraepithelial lesions and vaginal and vulvar diseases. All images were received
without distortions in color, size, or orientation. With complete visualization of the
squamocolumnar junction there was an 86% agreement between the remote and
review sites (k=.533, P=.019). The interobserver agreement for colposcopic
impressions was 86% (κ=.684, P <.001), and for colposcopic impressions with
histology within one level of disease severity, 86%(k=.78,P <.001).Colposcopists'
and patients' satisfaction with telecolposcopy was excellent. More than 95% of
the women stated that they would rather have their colposcopy locally with
electronic transmission if an experienced colposcopist were more than 25 miles
away. CONCLUSIONS: The telecolposcopic system described in our study is
technically feasible, can be implemented in an office system with limited technical
support, and is preferred by women who have to travel many miles to receive
referral health care.
Homa, K. (2004). "A conceptual idea to improve access in a complex health care
system." Quality Management in Health Care 13(4): 243-263.
OBJECTIVE: The purpose of this article was to briefly describe the Open Access
model, a method of improving access to a health care organization, and a
conceptual idea is proposed for complex organizations that want to engage in
this improvement work. The target audience is health care organizations that
want to improve access to their services but are challenged by the complexity of
their processes. METHODS: A case study presents an organization's experience
with the Open Access assessment process. This process starts with quantifying
an organization's supply and demand and then deciding how to reshape its
capacity and implement other strategies. A high-leverage area to improve access
is a standardized or predictable process that is streamlined or implemented for a
specific group of patients. RESULTS: Health care organizations are complex and
have processes of care that are not explicit, in which services are rendered
uniquely for each individual patient and it is difficult to see the harmony or
patterns in how the work is done. CONCLUSION: The underlying principles of
the Open Access model can be adopted in a complex organization, if it is
acceptable to do more exploratory work and create or increase opportunities for
the right things to happen.
Kerlikowske, K., P. A. Carney, B. Geller, M. T. Mandelson, S. H. Taplin, K. Malvin, V.
Ernster, N. Urban, G. Cutter, R. Rosenberg and R. Ballard-Barbash (2000).
"Performance of screening mammography among women with and without a firstdegree relative with breast cancer." Ann Intern Med 133(11): 855-63.
BACKGROUND: Although it is recommended that women with a family history of
breast cancer begin screening mammography at a younger age than averagerisk women, few studies have evaluated the performance of mammography in
this group. OBJECTIVE: To compare the performance of screening
mammography in women with a first-degree family history of breast cancer and
women of similar age without such history. DESIGN: Cross-sectional. SETTING:
Mammography registries in California (n = 1), New Hampshire (n = 1), New
Mexico (n = 1), Vermont (n = 1), Washington State n = 2), and Colorado (n = 1).
Emerging Issues175
PARTICIPANTS: 389 533 women 30 to 69 years of age who were referred for
screening mammography from April 1985 to November 1997.
MEASUREMENTS: Risk factors for breast cancer; results of first screening
examination captured for a woman by a registry; and any invasive cancer or
ductal carcinoma in situ identified by linkage to a pathology database, the
Surveillance, Epidemiology, and End Results program, or a state tumor registry.
RESULTS: The number of cancer cases per 1000 examinations increased with
age and was higher in women with a family history of breast cancer than in those
without (3.2 vs. 1.6 for ages 30 to 39 years, 4.7 vs. 2.7 for ages 40 to 49 years,
6.6 vs. 4.6 for ages 50 to 59 years, and 9.3 vs. 6.9 for ages 60 to 69 years). The
sensitivity of mammography increased significantly with age (P = 0.001 [chisquare test for trend]) in women with a family history and in those without (63.2%
[95% CI, 41. 5% to 84.8%] vs. 69.5% [CI, 57.7% to 81.2%] for ages 30 to 39
years, 70.2% [CI, 61.0% to 79.5%] vs. 77.5% [CI, 73.3% to 81.8%] for ages 40 to
49 years, 81.3% [CI, 73.3% to 89.3%] vs. 80.2% [CI, 76.5% to 83.9%] for ages
50 to 59 years, and 83.8% [CI, 76.8% to 90.9%] vs. 87.7% [CI, 84.8% to 90.7%]
for ages 60 to 69 years). Sensitivity was similar for each decade of age
regardless of family history. The positive predictive value of mammography was
higher in women with a family history than in those without (3.7% vs. 2.9%; P =
0.001). CONCLUSIONS: Cancer detection rates in women who had a firstdegree relative with a history of breast cancer were similar to those in women a
decade older without such a history. The sensitivity of screening mammography
was influenced primarily by age.
Kieran, S., L. J. Loescher and K. H. Lim (2007). "The role of financial factors in
acceptance of clinical BRCA genetic testing." Genet Test 11(1): 101-10.
Many women who are offered BRCA genetic testing by genetics professionals do
not have the test, possibly for financial reasons. We explored financial factors
implicated in non-uptake of BRCA testing in women who had received genetic
counseling in a clinical setting. Specifically, we described financial factors
(affordability, health insurance, other) involved with BRCA testing; compared
nonfinancial factors (disease, sociodemographic, risk assessment) in women
who did not have BRCA testing (nontesters) with women who had the test
(testers); showed associations of financial and nonfinancial factors with BRCA
testing; and identified predictors of non-uptake of BRCA testing. The sample of
100 women (64 nontesters and 36 testers) completed an anonymous mailed
survey on financial factors; 52 of the nontesters answered questions about
nonfinancial factors. Testers had significantly better affordability and insurance
coverage (p < 0.001), more diagnoses of breast or ovarian cancer (p < 0.05) and
higher rates of receiving post-counseling risk estimates (p < 0.05), than
nontesters. Non-uptake was 5.5-fold more likely in women that could not afford
full or partial payment for the test and was 15.5-fold more likely in women that did
not recall receiving risk estimates post-counseling. For many women having risk
factors for breast/ovarian cancer, affordability of BRCA testing and insurance
coverage for the test remain problematic. Post-counseling reminders of risk
estimates may contribute to uptake of testing.
Emerging Issues176
New Hampshire Advisory Committee to the United States Commission on Civil Rights
(2005). Language and Access to Health Care: Easing Barriers in New Hampshire: 35.
The report provides information pertaining to all aspects of Health Care Access in
the state of New Hampshire. Topics discussed include New Hampshire
Demographics, Federal and State Civil Rights Regulations and Policies, Health
Care Provider Practices and Perspectives, and Client Advocate Perspectives.
The report was prepared for the United States Commission on Civil Rights.
Ross JS, Bernheim SM, Bradley EH, Teng HM, Gallo WT. (2007). "Use of preventive
care by the working poor in the United States." Preventitive medicine 44(3): 254-259.
OBJECTIVE: Examine the association between poverty and preventive care use
among older working adults. METHOD: Cross-sectional analysis of the pooled
1996, 1998 and 2000 waves of the Health and Retirement Study, a nationally
representative sample of older community-dwelling adults, studying self-reported
use of cervical, breast, and prostate cancer screening, as well as serum
cholesterol screening and influenza vaccination. Adults with incomes within
200% of the federal poverty level were defined as poor. RESULTS: Among
10,088 older working adults, overall preventive care use ranged from 38%
(influenza vaccination) to 76% (breast cancer screening). In unadjusted
analyses, the working poor were significantly less likely to receive preventive
care. After adjustment for insurance coverage, education, and other sociodemographic characteristics, the working poor remained significantly less likely to
receive breast cancer (RR 0.92, 95% CI, 0.86-0.96), prostate cancer (RR 0.89,
95% CI, 0.81-0.97), and cholesterol screening (RR 0.91, 95% CI, 0.86-0.96) than
the working non-poor, but were not significantly less likely to receive cervical
cancer screening (RR 0.96, 95% CI, 0.90-1.01) or influenza vaccination (RR
0.92, 95% CI, 0.84-1.01). CONCLUSION: The older working poor are at
modestly increased risk for not receiving preventive care.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Health Care Access. Nancy Ryan. Lee, NH, New Hampshire Breast
Cancer Coalition.
Access to quality health care for all is the National Breast Cancer Coalition's top
legislative priority:
(http://www.stopbreastcancer.org/bin/index.asp?Strid=20&depid=3). Our work to
end breast cancer will not be realized until everyone has access to evidencebased screening and treatment.
Emerging Issues177
Breast and Cervical Cancer
General
Dietrich, A. J., J. N. Tobin, et al. (2006). "Telephone care management to improve
cancer screening among low-income women: a randomized, controlled trial." Ann Intern
Med 144(8): 563-71.
BACKGROUND: Minority and low-income women receive fewer cancer
screenings than other women. OBJECTIVE: To evaluate the effect of a
telephone support intervention to increase rates of breast, cervical, and
colorectal cancer screening among minority and low-income women. DESIGN:
Randomized, controlled trial conducted between November 2001 and April 2004.
SETTING: 11 community and migrant health centers in New York City.
PATIENTS: 1413 women who were overdue for cancer screening.
INTERVENTION: Over 18 months, women assigned to the intervention group
received an average of 4 calls from prevention care managers and women
assigned to the control group received usual care. Follow-up data were available
for 99% of women, and 91% of the intervention group received at least 1 call.
MEASUREMENTS: Medical record documentation of mammography,
Papanicolaou testing, and colorectal cancer screening according to U.S.
Preventive Services Task Force recommendations. RESULTS: The proportion of
women who had mammography increased from 0.58 to 0.68 with the intervention
and decreased from 0.60 to 0.58 with usual care; the proportion who had
Papanicolaou testing increased from 0.71 to 0.78 with the intervention and was
unchanged with usual care; and the proportion who had colorectal screening
increased from 0.39 to 0.63 with the intervention and from 0.39 to 0.50 with usual
care. The difference in the change in screening rates between groups was 0.12
for mammography (95% CI, 0.06 to 0.19), 0.07 for Papanicolaou testing (CI, 0.01
to 0.12), and 0.13 for colorectal screening (CI, 0.07 to 0.19). The proportion of
women who were up to date for 3 tests increased from 0.21 to 0.43 with the
intervention. LIMITATIONS: Participants were from 1 city and had access to a
regular source of care. Medical records may not have captured all cancer
screenings. CONCLUSIONS: Telephone support can improve cancer screening
rates among women who visit community and migrant health centers. The
intervention seems to be well suited to health plans, large medical groups, and
other organizations that seek to increase cancer screening rates and to address
disparities in care.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Knowing Risk Factors and Imaging. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
An example of why this is relevant is the American Cancer Society (ACS) new
Magnetic Resonance Imaging (MRI) recommendation. ACS recently
recommended magnetic resonance imaging, in addition to mammograms, for
Emerging Issues178
very high risk women. Unfortunately, most women do not know what risk
category they are in, nor is it a simple matter to define risk since there are
several risk models available for doctors and patients to use. Most women who
are diagnosed with breast cancer have none of the known risk factors. See the
ACS web site:
http://www.cancer.org/docroot/MED/content/MED_2_1x_American_Cancer_Soci
ety_Issues_Recommendation_on_MRI_for_Breast_Cancer_Screening.asp
In response to these new MRI guidelines, the National Breast Cancer Coalition Fund
(NBCCF) noted the lack of standards for equipment and MRI reader competency
as well as the high cost. NBCCF is concerned because none of the clinical
studies on which the ACS recommendation is based was a randomized
controlled trial, the generally accepted standard as the basis for a conclusive
result. There is also a lack of data on whether MRI screening decreases breast
cancer mortality, an important goal for a screening program. If MRI availability
and use becomes widespread, NBCCF points out it is unlikely that randomized
clinical trials will ever be conducted to assess its effect on mortality.
Titus-Ernstoff, L., A. N. Tosteson, C. Kasales, J. Weiss, M. Goodrich, E. E. Hatch and
P. A. Carney (2006). "Breast cancer risk factors in relation to breast density (United
States)." Cancer Causes Control 17(10): 1281-90.
OBJECTIVES: Evaluate known breast cancer risk factors in relation to breast
density. METHODS: We examined factors in relation to breast density in 144,018
New Hampshire (NH) women with at least one mammogram recorded in a
statewide mammography registry. Mammographic breast density was measured
by radiologists using the BI-RADS classification; risk factors of interest were
obtained from patient intake forms and questionnaires. RESULTS: Initial
analyses showed a strong inverse influence of age and body mass index (BMI)
on breast density. In addition, women with late age at menarche, late age at first
birth, premenopausal women, and those currently using hormone therapy (HT)
tended to have higher breast density, while those with greater parity tended to
have less dense breasts. Analyses stratified on age and BMI suggested
interactions, which were formally assessed in a multivariable model. The impact
of current HT use, relative to nonuse, differed across age groups, with an inverse
association in younger women, and a positive association in older women (p <
0.0001 for the interaction). The positive effects of age at menarche and age at
first birth, and the inverse influence of parity were less apparent in women with
low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01,
respectively, for the interactions). We also noted stronger positive effects for age
at first birth in postmenopausal women (p = 0.004 for the interaction). The
multivariable model indicated a slight positive influence of family history of breast
cancer. CONCLUSIONS: The influence of age at menarche and reproductive
factors on breast density is less evident in women with high BMI. Density is
reduced in young women using HT, but increased in HT users of age 50 or more.
Emerging Issues179
Meissner, Helen I., Robert A. Smith, Barbara K. Rimer, Katherine M. Wilson, William
Rakowski, Sally W. Vernon and Peter A. Briss (2004). "Promoting cancer screening:
Learning from experience." Cancer 101(S5): 1107-1117.
This article provides an overview of behavioral and social science cancer
screening intervention research and introduces the scope of topics addressed in
this supplement to Cancer. The authors identify and address issues to consider
before conducting interventions to promote the uptake of screening tests, such
as the benefits and harms associated with screening. Trends in the use of cancer
screening tests are discussed in the context of their efficacy and adoption over
time. Both the development and breadth of social and behavioral intervention
research intended to increase the use of effective tests are reviewed as
background for the articles that follow. The application of the lessons from this
extensive knowledge base not only should accelerate the uptake of the effective
cancer screening tests currently available, but also can guide future directions for
research. Cancer 2004. Published 2004 by the American Cancer Society.
New Hampshire Department of Health & Human Services. (2007). "Breast and Cervical
Cancer Program." from http://www.dhhs.state.nh.us/DHHS/CDPC/bccp.htm.
DHHS has provided funding for a Breast and Cervical Cancer Screening
Program since 1985. In 1990, the US Congress passed the Breast and Cervical
Cancer Mortality Prevention Act that mandated and provided funding for the
National Breast and Cervical Cancer Early Detection Program.
Cervical Cancer Prevention and Screening
Associated Press. (2006, November 30, 2006). "N.H. first state to offer girls free cancer
vaccine." Associated Press Retrieved June 2, 2007, 2007, from
http://www.msnbc.msn.com/id/15958573/.
Associated Press article about New Hampshire's efforts to offer the HPVvaccination to all girls.
Balluz, L., I. B. Ahluwalia, et al. (2004). "Surveillance for certain health behaviors among
selected local areas--United States, Behavioral Risk Factor Surveillance System, 2002."
MMWR Surveill Summ 53(5): 1-100.
PROBLEM: Monitoring risk behaviors for chronic diseases and participation in
preventive practices are important for developing effective health education and
intervention programs to prevent morbidity and mortality. Therefore, continual
monitoring of these behaviors and practices at the state, city, and county levels
can assist public health programs in evaluating and monitoring progress toward
improving their community's health. REPORTING PERIOD COVERED: Data
collected in 2002 are presented for states, selected metropolitan, and
micropolitan statistical areas (MMSA), and their counties. DESCRIPTION OF
THE SYSTEM: The Behavioral Risk Factor Surveillance System (BRFSS) is an
on-going, state-based, telephone survey of the civilian, noninstitutionalized
population aged >18 years. All 50 states, the District of Columbia (DC), Guam,
the Virgin Islands, and the Commonwealth of Puerto Rico participated in BRFSS
Emerging Issues180
during 2002. Metropolitan and MMSA and their counties with >500 respondents
or a minimum sample size of 19 per weighting class were included in the
analyses for a total of 98 MMSA and 146 counties. RESULTS: Prevalence of
high-risk behaviors for chronic diseases, awareness of certain medical
conditions, and use of preventive health-care services varied substantially by
state, county, and MMSA. Obesity ranged from 27.6% in West Virginia, 29.4% in
Charleston, West Virginia, and 32.0% in Florence County, South Carolina, to
16.5% in Colorado, 12.8% in Bethesda-Frederick-Gaithersburg, Maryland, and
11.8% in Washington County, Rhode Island. No leisuretime physical activity
ranged from 33.6% in Tennessee, 36.8% in Miami-Miami Beach-Kendall, Florida,
and 36.8% in Miami-Dade County, Florida to 15.0% in Washington, 13.8% in
Seattle-Bellevue-Everett Washington, and 11.4% in King County, Washington.
Cigarette smoking ranged from 32.6% in Kentucky, 32.8% in YoungstownWarren- Boardman, Ohio-Pennsylvania, and 31.1% in Jefferson County,
Kentucky to 16.4% in California, 13.8% in Ogden- Clearfield, Utah, and 10.9% in
Davis County, Utah. Binge drinking ranged from 24.9% in Wisconsin, 26.1% in
Fargo, North Dakota-Minnesota, and 25.1% Cass County, North Dakota, to 7.9%
in Kentucky, 8.2% in Greensboro- High Point, North Carolina, and 6.6% in
Henderson County, North Carolina. At risk for heavy drinking ranged from 8.7%
in Arizona, 9.5% in Lebanon, New Hampshire-Vermont, and 11.3% in Richland
County, South Carolina, to 2.8% in Utah, 1.9% in Ogden-Clearfield, Utah, and
1.7% in King County, New York. Adults who were told they had diabetes ranged
from 10.2% in West Virginia, 11.1% in Charleston, West Virginia, and 11.1% in
Richland, South Carolina, to 3.5% in Alaska, 2.7% in Anchorage, Alaska, and
2.4% in Weber County, Utah. Percentage of adults aged>50 years who were
ever screened for colorectal cancer ranged from 64.8% in Minnesota, 67.9% in
Minneapolis-St. Paul-Bloomington Minnesota-Wisconsin, and 73.6% in Ramsey
County, Minnesota, to 39.2% in Hawaii, 30.7% in Kahului-Wailuku, Hawaii, and
30.7% in Maui County, Hawaii. Persons aged >65 years who had received
pneumococcal vaccine ranged from 72.5% in North Dakota, 74.8% in
Minneapolis-St. Paul-Bloomington, Minnesota-Wisconsin, and 73.1% in
Milwaukee County, Wisconsin, to 47.9% in DC, 47.5% in New York-Wayne-White
Plains, New York, New Jersey, and 47.9% in DC County, DC. Older adults who
had received influenza vaccine ranged from 76.6% in Minnesota, 80.0% in
Minneapolis-St. Paul-Bloomington, Minnesota-Wisconsin, and 76.3% in
Middlesex County, Massachusetts, to 57.0% in Florida, 55.8% in HoustonBaytown-Sugar Land, Texas, and 56.2% in Cook County, Illinois.
INTERPRETATION: BRFSS data indicate substantial variation in high-risk
behaviors, participation in preventive healthcare services, and screening among
U.S. adults at states and selected local areas, indicating a need for continued
efforts to evaluate public health programs or policies designed to reduce
morbidity and mortality. PUBLIC HEALTH ACTIONS: Data from BRFSS are
useful in developing and guiding public health programs and policies. Therefore,
states, selected MMSA, and their counties can use BRFSS data as a tool to
prevent premature morbidity and mortality among adult population and to assess
progress toward national health objectives. The data indicate a continued need to
Emerging Issues181
develop and implement health promotion programs for targeting specific
behaviors and practices and serve as a baseline for future surveillance at the
local level in the United States.
Burak, L. J. and M. Meyer (1997). "Using the Health Belief Model to examine and
predict college women's cervical cancer screening beliefs and behavior." Health Care
Women Int 18(3): 251-62.
The high prevalence of human papillomavirus (HPV) among adolescent and
young adult women and the causal association between certain types of HPV
and cervical cancer make regular gynecological screening and Pap smear testing
essential health practices for young women. In this study, we used the constructs
of the Health Belief Model (HBM) to examine the gynecological screening beliefs
and behaviors of a sample of 400 college women. Although the constructs of the
model were able to explain only 15% of the variance in screening behavior and
11% of screening intentions, the use of the HBM framework resulted in important
information regarding the participants' beliefs.
Carney, P., A. J. Dietrich, et al. (1992). "Improving future preventive care through
educational efforts at a women's community screening program." J Community Health
17(3): 167-74.
Cervical cancer mortality continues to be a significant problem in the United
States. Pap Test screening programs have been effective in attracting high risk
women, but the impact of these programs on subsequent health care has seldom
been explored. This follow up study examined the impact of a cervical cancer
screening and education program on preventive health behaviors of New
Hampshire women in the 24 months following the screening program. A mailed
survey was sent to a random sample of 750 women from program participants to
evaluate both their recent preventive health care practices and to identify
perceived barriers to obtaining preventive health services. Of these, 71.1 percent
responded. Survey responses of the original program participants were linked to
each subject's previous answers to the same questions asked 24 months earlier.
A comparison group was derived by asking follow up study participants to identify
a female acquaintance within five years of her age. Seventy-four percent of the
comparison group responded. Survey responses of original program participants
were then compared to those of the comparison group. Results indicate that
women who participated in the original Project received significantly more
preventive health care services in the two years since the Project than in the two
years prior to it. Women in the comparison group received more Paps and
clinical breast examinations than women in the participant group, perhaps
because all participants had received a Pap test two years before. Having a
regular health care provider was the most significant characteristic associated
with obtaining indicated preventive services. An important contribution of
community screening programs may be to encourage women to establish a
regular source of care.
Emerging Issues182
Dietrich, A. J., P. Carney-Gersten, et al. (1989). "Community screening for cervical
cancer in New Hampshire." J Fam Pract 29(3): 319, 321, 323.
Dietrich, A. J., J. N. Tobin, et al. (2006). "Telephone care management to improve
cancer screening among low-income women: a randomized, controlled trial." Ann Intern
Med 144(8): 563-71.
BACKGROUND: Minority and low-income women receive fewer cancer
screenings than other women. OBJECTIVE: To evaluate the effect of a
telephone support intervention to increase rates of breast, cervical, and
colorectal cancer screening among minority and low-income women. DESIGN:
Randomized, controlled trial conducted between November 2001 and April 2004.
SETTING: 11 community and migrant health centers in New York City.
PATIENTS: 1413 women who were overdue for cancer screening.
INTERVENTION: Over 18 months, women assigned to the intervention group
received an average of 4 calls from prevention care managers and women
assigned to the control group received usual care. Follow-up data were available
for 99% of women, and 91% of the intervention group received at least 1 call.
MEASUREMENTS: Medical record documentation of mammography,
Papanicolaou testing, and colorectal cancer screening according to U.S.
Preventive Services Task Force recommendations. RESULTS: The proportion of
women who had mammography increased from 0.58 to 0.68 with the intervention
and decreased from 0.60 to 0.58 with usual care; the proportion who had
Papanicolaou testing increased from 0.71 to 0.78 with the intervention and was
unchanged with usual care; and the proportion who had colorectal screening
increased from 0.39 to 0.63 with the intervention and from 0.39 to 0.50 with usual
care. The difference in the change in screening rates between groups was 0.12
for mammography (95% CI, 0.06 to 0.19), 0.07 for Papanicolaou testing (CI, 0.01
to 0.12), and 0.13 for colorectal screening (CI, 0.07 to 0.19). The proportion of
women who were up to date for 3 tests increased from 0.21 to 0.43 with the
intervention. LIMITATIONS: Participants were from 1 city and had access to a
regular source of care. Medical records may not have captured all cancer
screenings. CONCLUSIONS: Telephone support can improve cancer screening
rates among women who visit community and migrant health centers. The
intervention seems to be well suited to health plans, large medical groups, and
other organizations that seek to increase cancer screening rates and to address
disparities in care.
Harper, D., E. Franco, et al. (2006). "Sustained efficacy up to 4.5 years of a bivalent L1
virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from
a randomised control trial." Lancet 267(9518): 1247-1255.
BACKGROUND: Effective vaccination against HPV 16 and HPV 18 to prevent
cervical cancer will require a high level of sustained protection against infection
and precancerous lesions. Our aim was to assess the long-term efficacy,
immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04
vaccine against incident and persistent infection with HPV 16 and HPV 18 and
their associated cytological and histological outcomes. METHODS: We did a
Emerging Issues183
follow-up study of our multicentre, double-blind, randomised, placebo-controlled
trial reported in 2004. We included women who originally received all three doses
of bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or
placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly
cervical cytology assessments. We also studied the long-term immunogenicity
and safety of the vaccine. FINDINGS: More than 98% seropositivity was
maintained for HPV-16/18 antibodies during the extended follow-up phase. We
noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints:
incident infection, 96.9% (95% CI 81.3-99.9); persistent infection: 6 month
definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). In a combined
analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of
100% (42.4-100) against cervical intraepithelial neoplasia (CIN) lesions
associated with vaccine types. We noted broad protection against
cytohistological outcomes beyond that anticipated for HPV 16/18 and protection
against incident infection with HPV 45 and HPV 31. The vaccine has a good
long-term safety profile. INTERPRETATION: Up to 4.5 years, the HPV-16/18 L1
virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a
high degree of protection against HPV-16/18 infection and associated cervical
lesions. There is also evidence of cross protection.
Harper, D. M., M. M. Moncur, et al. (2000). "The technical performance and clinical
feasibility of telecolposcopy." J Fam Pract 49(7): 623-7.
BACKGROUND: The purpose of our study was to demonstrate the technical
performance and clinical feasibility of a telecolposcopic system through
assessment of image transmission veracity, ease of office system
implementation, and the patient's acceptance of the electronic image
transmission. METHODS: We used a telecolposcopic system incorporating a
custom software package that integrated patient history, current gynecologic
status, epidemiologic risk factors, and colposcopic images for local medical
documentation and transmission. Satisfaction questionnaires were developed to
measure ease of implementation at the remote sites and the patients' acceptance
of telecolposcopy. RESULTS: Seventy-nine women participated in our trial. From
3 to 20 images were captured for each woman, documenting cervical squamous
intraepithelial lesions and vaginal and vulvar diseases. All images were received
without distortions in color, size, or orientation. With complete visualization of the
squamocolumnar junction there was an 86% agreement between the remote and
review sites (kappa=.533, P=.019). The interobserver agreement for colposcopic
impressions was 86% (kappa=.684, P <.001), and for colposcopic impressions
with histology within one level of disease severity, 86% (kappa=.78, P <.001).
Colposcopists' and patients' satisfaction with telecolposcopy was excellent. More
than 95% of the women stated that they would rather have their colposcopy
locally with electronic transmission if an experienced colposcopist were more
than 25 miles away. CONCLUSIONS: The telecolposcopic system described in
our study is technically feasible, can be implemented in an office system with
limited technical support, and is preferred by women who have to travel many
miles to receive referral health care.
Emerging Issues184
Harper, D. M., K. M. Parke, et al. (2000). "Self-reported desire to improve colposcopic
impressions." Arch Gynecol Obstet 264(3): 137-42.
BACKGROUND: Women who participate in cervical cancer screening programs
must have access to high quality colposcopy services when their cytology test
are abnormal. The purpose of this project is to evaluate colposcopic services
currently available in New Hampshire and whether colposcopy providers are
willing to network to maintain and improve their colposcopic pattern recognition
skills in order to improve their colposcopic correlations. METHODS: A survey
was mailed to 1314 providers throughout New Hampshire. The survey
ascertained the extent of current colposcopic services in New Hampshire through
practitioner and practice demographics, the cervical procedures performed, the
self-reported colposcopy skill level, and the self-reported quality of past
colposcopic education. It also measured interest in networking with others to
improve their colposcopic pattern recognition skills. RESULTS: The survey
response rate was 62%. 145 of the 810 respondents (18%) are currently
performing colposcopies, indicating a statewide potential colposcopy
accommodation rate of 3.5 to 7 women per month per colposcopist. 57% of the
physician assistants, 59% of the family physicians, 75% of the gynecologists and
100% of the nurse practitioners were interested in enhancing their colposcopic
pattern recognition skills by networking through quarterly meetings.
CONCLUSIONS: The crude accommodation rate for colposcopy appears
sufficient for the women of New Hampshire although the geographic distribution
of the colposcopists is unknown. A majority of the colposcopists were interested
in networking to improve their colposcopic pattern recognition skills, which could
improve patient care.
Mount, S. L. and J. L. Papillo (1999). "A study of 10,296 pediatric and adolescent
Papanicolaou smear diagnoses in northern New England." Pediatrics 103(3): 539-45.
OBJECTIVE: This study analyzes pediatric and adolescent Papanicolaou (Pap)
smear diagnoses to determine the prevalence rates of squamous intraepithelial
lesion (SIL) as well as infectious and reactive processes in this age group.
DESIGN: A total of 10 296 Pap smear diagnoses from patients 10 to 19 years of
age collected over a 1-year period and classified according to the Bethesda
system were reviewed. This population was almost exclusively white, the majority
residing in rural or suburban areas of Maine, New Hampshire, and Vermont. The
percentage of abnormal smear results was then compared with data generated
for older age subsets. RESULTS: The following diagnoses were made on 10 296
Pap smears from patients 10 to 19 years of age: 7208 (70.01%) normal; 1689
(16.4%) benign cellular change; 1004 (9.75%) atypical squamous cells of
undetermined significance; 388 (3.77%) squamous intraepithelial lesion (SIL);
and 7 (0.06%) atypical glandular cells of undetermined significance. A total of
1503 (14.6%) of smears showed infectious processes. Compared with the results
of adult Pap smears collected over the same time period, the age 20 to 29 subset
with 27 067 Pap smears and the age 30+ subset with 42 617 Pap smears
showed 11.79% and 8.43% infectious processes and 3.49% and 1.27% SIL,
Emerging Issues185
respectively. Therefore, the highest rate of infectious processes and SIL was
found in the subset of patients age 10 to 19 years. CONCLUSIONS: Because the
development of SIL and hence cervical cancer is causally related to sexually
transmitted human papilloma virus (HPV) infection, this high rate of abnormal
Pap smear results of both an infectious and precancerous nature in this
population may reflect a high level of sexual activity among adolescent girls.
These data reinforce the importance of implementing early cervical Pap smear
screening in the sexually active pediatric and adolescent population.
New Hampshire Department of Health & Human Services. (2007). "Breast and Cervical
Cancer Program." from http://www.dhhs.state.nh.us/DHHS/CDPC/bccp.htm.
DHHS has provided funding for a Breast and Cervical Cancer Screening
Program since 1985. In 1990, the US Congress passed the Breast and Cervical
Cancer Mortality Prevention Act that mandated and provided funding for the
National Breast and Cervical Cancer Early Detection Program.
Sirovich, B. E., D. J. Gottlieb, et al. (2003). "The burden of prevention: downstream
consequences of Pap smear testing in the elderly." J Med Screen 10(4): 189-95.
Context: Although cervical cancer is an unusual cause of death among women
65 and older, most elderly women in the US report continuing to undergo periodic
Pap smear screening. OBJECTIVE: To describe the incidence of Pap smears
and downstream testing among elderly women. SETTING: Claims-based
analysis of female Medicare enrollees age 65 and older. METHODS: Using three
years of Medicare Part B 5% Files (1995-1997), we differentiated between
women undergoing screening Pap smears and those undergoing Pap smears for
surveillance of previous abnormalities or Pap smear follow-up. We determined
the proportion of elderly women undergoing Pap smear testing and rates of
downstream testing and procedures after an initial Pap smear. RESULTS: Four
million female Medicare beneficiaries over 65 years underwent Pap smear
testing between 1995 and 1997, representing 25% of the eligible population.
After adjusting for underbilling for Pap smears under Medicare, 43% of women
over 65 are estimated to have undergone Pap smear testing during the 3-year
period. The large majority (90%) of Pap smears were for screening, while 10%
were done for surveillance or follow-up. For every 1000 women with a screening
Pap smear, 39 had at least one downstream intervention within eight months of
the initial Pap smear, including seven women who underwent colposcopy and
two women who had other surgical procedures. Rates of downstream
interventions were considerably higher for women undergoing Pap smear followup (302 per 1000 with at least one downstream intervention), and surveillance of
previous abnormalities (209 per 1000 with a downstream intervention).
CONCLUSION: Cervical cancer screening is widespread among elderly
American women, and follow-up testing is not uncommon, particularly among the
ten percent of women who appear to be in a cycle of repeated testing. This
substantial volume of testing occurs despite the rarity of cervical cancer deaths
and unknown benefits of screening in this age group.
Emerging Issues186
Genetic Testing
Fu, R., E. L. Harris, et al. (2007). "Estimating risk of breast cancer in carriers of BRCA1
and BRCA2 mutations: a meta-analytic approach." Stat Med 26(8): 1775-87.
Estimates of penetrance (or risk) of breast cancer among BRCA mutation
carriers in published studies are heterogeneous, prohibiting direct combined
estimates. Estimates of prevalence of BRCA mutations are more homogeneous
and could allow combined estimates of prevalence. We propose a combined
estimator of penetrance from combined estimates of the prevalence of BRCA
mutations in women with and without breast cancer and from the probability of
breast cancer by using Bayes' Theorem. The relative risk of having breast cancer
with positive family history and the prevalence of positive family history contribute
to the combined estimate of penetrance if family history is present. The combined
estimate incorporates variation in estimates from different resources. The method
is illustrated by using data from Ashkenazi Jewish women unselected for family
history and for those with family history. Risks of breast cancer conferred by
BRCA1 and BRCA2 mutations are estimated to be 8.39 per cent (6.56, 10.68 per
cent) and 2.66 per cent (1.85, 3.82 per cent) by 40 years old, and 47.45 per cent
(37.39, 57.72 per cent) and 31.85 per cent (23.72, 41.26 per cent) by 75 years
old, respectively. For those with family history, risks of breast cancer conferred
by BRCA mutations appear to be higher.
Kenen, R. H., P. J. Shapiro, et al. (2007). "Peer-support in coping with medical
uncertainty: discussion of oophorectomy and hormone replacement therapy on a webbased message board." Psychooncology.
The Facing Our Risk of Cancer Empowered (FORCE) website is devoted to
women at risk for hereditary breast and ovarian cancers (HBOC). To understand
the unique health concerns and emotional support needs of these women, we
examined threads on the FORCE archived message boards with relevance to the
broader HBOC community. We report on a thread discussing the controversial
decision to use hormone replacement therapy (HRT) following prophylactic
oophorectomy (PO). We used a qualitative research inductive process involving
close reading, coding and identification of recurrent patterns, relationships and
processes in the data. Twenty-nine women posted 177 messages over 7 months.
Two main groups of women posted: (1) Women who were BRCA+, had
completed PO, and were debating or adjusting their HRT options in terms of
optimizing both quality and quantity of life. (2) Women who were BRCA+, were
contemplating PO, but wanted to better understand the potential physical and
psychological consequences of surgical menopause before deciding. Frustrated
by physicians' lack of knowledge and contradictory media articles about the longterm consequences of HRT in BRCA+ women, they sought resources, emotional
support and specific experiential knowledge from each other and generated a
unique sense of community and a high level of trust.
Kieran, S., L. J. Loescher, et al. (2007). "The role of financial factors in acceptance of
clinical BRCA genetic testing." Genet Test 11(1): 101-10.
Emerging Issues187
Many women who are offered BRCA genetic testing by genetics professionals do
not have the test, possibly for financial reasons. We explored financial factors
implicated in non-uptake of BRCA testing in women who had received genetic
counseling in a clinical setting. Specifically, we described financial factors
(affordability, health insurance, other) involved with BRCA testing; compared
nonfinancial factors (disease, sociodemographic, risk assessment) in women
who did not have BRCA testing (nontesters) with women who had the test
(testers); showed associations of financial and nonfinancial factors with BRCA
testing; and identified predictors of non-uptake of BRCA testing. The sample of
100 women (64 nontesters and 36 testers) completed an anonymous mailed
survey on financial factors; 52 of the nontesters answered questions about
nonfinancial factors. Testers had significantly better affordability and insurance
coverage (p < 0.001), more diagnoses of breast or ovarian cancer (p < 0.05) and
higher rates of receiving post-counseling risk estimates (p < 0.05), than
nontesters. Non-uptake was 5.5-fold more likely in women that could not afford
full or partial payment for the test and was 15.5-fold more likely in women that did
not recall receiving risk estimates post-counseling. For many women having risk
factors for breast/ovarian cancer, affordability of BRCA testing and insurance
coverage for the test remain problematic. Post-counseling reminders of risk
estimates may contribute to uptake of testing.
McBride, D. (2007). "Test to Predict Breast Cancer Relapse Approved by FDA." ONS
Connect 22(5): 7-7.
The article reports on the approval given by the U.S. Food and Drug
Administration to MammaPrint, a prognostic test from Molecular Profiling Institute
Inc. that profiles genetic activity to predict whether a breast cancer patient will
have a relapse. The test examines the pattern of activity of specific genes in
breast tumors after being removed by surgery. The article cites that the test will
help guide the treatment of U.S. women who are diagnosed with breast cancer.
Moller, P., D. G. Evans, et al. (2007). "Surveillance for familial breast cancer:
Differences in outcome according to BRCA mutation status." Int J Cancer 121(5): 101720.
Women with a family history of breast cancer are commonly offered regular
clinical or mammographic surveillance from age 30. Data on the efficacy of such
programmes are limited. Clinical, pathological and outcome data were recorded
on all breast and ovarian cancers diagnosed within familial breast cancer
surveillance programmes at collaborating centers in Norway and the UK up to the
end of 2005. These have been analyzed according to the mutation status of the
affected women (BRCA1+ve, BRCA2+ve or mutation-negative). Breast cancer
was diagnosed in 442 patients subsequently followed for a total of 2095 years.
Eighty-nine (20%) had BRCA1 mutations, 35 (8%) BRCA2 mutations and in 318
(72%) no mutation could be detected ("mut neg"). Five-year survival in BRCA1
was 73% compared to 96% in BRCA2 and 92% in mut neg (p = 0.000). Among
BRCA1 mutation-carriers, 5-year survival was 67% for cases diagnosed as
carcinoma in situ, 84% for node-negative invasive cancers and 58% for those
Emerging Issues188
with nodal involvement (p > 0.05). For BRCA2 mutation-carriers the
corresponding figures were 100, 100 and 90% (p > 0.05), while for mut neg
women they were 100, 97 and 71% (p = 0.03). Regular surveillance in women at
increased familial risk of breast cancer is associated with a good outcome if they
carry BRCA2 mutations or no detectable mutation. Carriers of BRCA1 mutations
fare significantly worse, even when their tumors are diagnosed at an apparently
early stage. The differences in outcome associated with different genetic causes
of disease were associated with demonstrated differences in tumor biology. The
findings demonstrate the outcome for genetically different breast cancers
detected within a programme for early diagnosis and treatment, which is relevant
to genetic counseling when women at risk have to chose between the options for
preventing death from inherited breast cancer. (c) 2007 Wiley-Liss, Inc.
Nisker, J. A. (2007). "The Need for Public Education: "Surveillance and Risk Reduction
Strategies" for Women at Risk for Carrying BRCA Gene Mutations." J Obstet Gynaecol
Can 29(6): 510-1.
Pal, T., J. Permuth-Wey, et al. (2007). "Improved survival in BRCA2 carriers with
ovarian cancer." Fam Cancer 6(1): 113-9.
OBJECTIVES: The objective of this study was to investigate survival of ovarian
cancer patients with BRCA1 and BRCA2 mutations compared to those without
mutations in a population-based sample of incident epithelial ovarian cancer
cases. METHODS: Follow-up for vital status was performed on a populationbased sample of 232 women with incident epithelial ovarian cancer recruited
between December 13, 2000 and September 30, 2003 in the Tampa Bay area.
Survival analysis using Cox regression was performed on (1) all 232 cases and
(2) the 209 invasive epithelial ovarian cancer cases. Results of the two analyses
were similar, thus data involving the 209 invasive epithelial cancer cases are
presented, as this was judged to be more clinically relevant. RESULTS: In the
multivariate analysis, BRCA status and stage were statistically significant, and
were adjusted for in the survival analysis model. The Kaplan-Meier method
estimated expected survival at 4 years of 83% of BRCA2 carriers compared to
37% of BRCA1 carriers and 12% of non-carriers. There was a statistically
significant difference between BRCA2 carriers and non-carriers (p = 0.013). No
statistically significant survival differences were seen for BRCA1 carriers when
compared with either BRCA2 carriers or non-carriers. CONCLUSION: These
data suggest that BRCA2 mutation carriers with ovarian cancer may have better
survival than BRCA1 carriers and non-carriers. The etiology of this possible
survival advantage is currently unknown. Larger studies are needed to confirm
these results and to clarify their etiology and clinical significance.
Rennert, G., S. Bisland-Naggan, et al. (2007). "Clinical outcomes of breast cancer in
carriers of BRCA1 and BRCA2 mutations." N Engl J Med 357(2): 115-23.
BACKGROUND: Some features of breast cancer in women with a BRCA1
mutation suggest that hereditary breast cancer has a poor outcome. We
conducted a national population-based study of Israeli women to determine the
Emerging Issues189
influence, if any, of a BRCA1 or a BRCA2 mutation on the prognosis in breast
cancer. METHODS: We obtained data on all incident cases of invasive breast
cancer that were diagnosed from January 1, 1987, to December 31, 1988, and
recorded in the Israel National Cancer Registry. We requested a paraffinembedded tumor block or an unstained slide and the corresponding pathological
and clinical records for all such cases. DNA extracted from the tumor specimens
was analyzed for the three founder mutations in BRCA1 and BRCA2. For each
subject, available pathological and oncologic records were reviewed. RESULTS:
We were able to retrieve a pathological sample from 1794 of 2514 subjects
(71%). Among those women, we obtained medical records for 1545 (86%). A
BRCA1 or BRCA2 mutation was identified in 10% of the women who were of
Ashkenazi Jewish ancestry. The adjusted hazard ratios for death from breast
cancer were not significantly different among mutation carriers and noncarriers
(hazard ratio among BRCA1 carriers, 0.76; 95% confidence interval [CI], 0.45 to
1.30; P=0.31; hazard ratio among BRCA2 carriers, 1.31; 95% CI, 0.80 to 2.15;
P=0.28). Among women who were treated with chemotherapy, the hazard ratio
for death among BRCA1 carriers was 0.48 (95% CI, 0.19 to 1.21; P=0.12).
CONCLUSIONS: Breast cancer-specific rates of death among Israeli women are
similar for carriers of a BRCA founder mutation and noncarriers.
Robson, M. (2007). "Is breast conservation a reasonable option for women with BRCAassociated breast cancer?" Nat Clin Pract Oncol 4(1): 10-1.
Sivell, S., R. Iredale, et al. (2007). "Cancer genetic risk assessment for individuals at
risk of familial breast cancer." Cochrane Database Syst Rev(2): CD003721.
BACKGROUND: The recognition of an inherited component to breast cancer has
led to an increase in demand for information, reassurance, and genetic testing,
resulting in the creation of genetics clinics for familial cancer. The first step for
patients referred to a cancer genetic clinic is a risk assessment. OBJECTIVES:
To evaluate the impact of cancer genetic risk assessment services on patients at
risk of familial breast cancer. SEARCH STRATEGY: The specialised register
maintained by the Cochrane Breast Cancer Group was searched. We also
searched MEDLINE, EMBASE, CINAHL, PsycLIT, CENTRAL, DARE, ASSIA,
Web of Science, SIGLE and LILACS. The searches covered the period 1985 to
February 2005. We also hand-searched relevant journals. SELECTION
CRITERIA: Trials looking at interventions for cancer genetic risk assessment
delivery for familial breast cancer were considered for inclusion. Trials assessed
outcomes such as understanding of risk, satisfaction and psychological wellbeing. Studies were excluded if they concerned cancers other than breast cancer
or if participants were not at risk of breast cancer. Trials concerning the provision
of information or education were also excluded as it was intended to review these
separately. Participants could be individuals of any age or gender, with or without
a known BRCA mutation, but without a previous history of breast cancer or any
other serious illness. DATA COLLECTION AND ANALYSIS: Two authors
independently assessed trial quality and extracted data. Additional information
was sought from investigators as necessary. Due to the heterogeneity of both the
Emerging Issues190
interventions and outcomes, data were analysed descriptively. MAIN RESULTS:
Fifty-eight papers were identified as relevant to the review, 54 of these were
subsequently excluded. The three included trials (pertaining to five papers),
provide data on 1251 participants and assessed the impact of cancer genetic risk
assessment on outcomes including perceived risk, and psychological distress.
This review suggests that cancer genetic risk assessment services help to
reduce distress, improve the accuracy of the perceived risk of, and increase
knowledge about, breast cancer and genetics. The health professional delivering
the risk assessment does not appear to have a significant impact on these
outcomes. AUTHORS' CONCLUSIONS: This review found favourable outcomes
for patients' risk assessment for familial breast cancer. However, there were too
few papers to make any significant conclusions about how best to deliver cancer
genetic risk assessment services. Further research is needed assessing the best
means of delivering cancer risk assessment, by different health professionals, in
different ways and in alternative locations.
Vidarsdottir, L., S. K. Bodvarsdottir, et al. (2007). "Breast cancer risk associated with
AURKA 91T -->A polymorphism in relation to BRCA mutations." Cancer Lett 250(2):
206-12.
In this study 759 breast cancer patients, including 9 BRCA1 and 98 BRCA2
mutation carriers, and 653 mutation-negative unaffected controls were genotyped
for the AURKA 91T -->A polymorphism. Individuals homozygous for the 91A
allele were found to be at increased risk of breast cancer compared to 91T
homozygotes (OR=1.87; 95% CI=1.09-3.21). This association was strengthened
when cases carrying BRCA mutations were excluded (OR=2.00; 95% CI=1.153.47). BRCA carrier cases differed from sporadic cases and their allele
distribution was very similar to controls. These results show a statistically
significant increased risk of sporadic breast cancer for individuals that are
homozygous for the 91A allele but no effect in carriers of BRCA mutations. This
may throw light on previously conflicting results.
Weitzel, J. N., V. I. Lagos, et al. (2007). "Limited family structure and BRCA gene
mutation status in single cases of breast cancer." JAMA 297(23): 2587-95.
CONTEXT: An autosomal dominant pattern of hereditary breast cancer may be
masked by small family size or transmission through males given sex-limited
expression. OBJECTIVE: To determine if BRCA gene mutations are more
prevalent among single cases of early onset breast cancer in families with limited
vs adequate family structure than would be predicted by currently available
probability models. DESIGN, SETTING, AND PARTICIPANTS: A total of 1543
women seen at US high-risk clinics for genetic cancer risk assessment and
BRCA gene testing were enrolled in a prospective registry study between April
1997 and February 2007. Three hundred six of these women had breast cancer
before age 50 years and no first- or second-degree relatives with breast or
ovarian cancers. MAIN OUTCOME MEASURE: The main outcome measure was
whether family structure, assessed from multigenerational pedigrees, predicts
BRCA gene mutation status. Limited family structure was defined as fewer than 2
Emerging Issues191
first- or second-degree female relatives surviving beyond age 45 years in either
lineage. Family structure effect and mutation probability by the Couch, Myriad,
and BRCAPRO models were assessed with stepwise multiple logistic regression.
Model sensitivity and specificity were determined and receiver operating
characteristic curves were generated. RESULTS: Family structure was limited in
153 cases (50%). BRCA gene mutations were detected in 13.7% of participants
with limited vs 5.2% with adequate family structure. Family structure was a
significant predictor of mutation status (odds ratio, 2.8; 95% confidence interval,
1.19-6.73; P = .02). Although none of the models performed well, receiver
operating characteristic analysis indicated that modification of BRCAPRO output
by a corrective probability index accounting for family structure was the most
accurate BRCA gene mutation status predictor (area under the curve, 0.72; 95%
confidence interval, 0.63-0.81; P<.001) for single cases of breast cancer.
CONCLUSIONS: Family structure can affect the accuracy of mutation probability
models. Genetic testing guidelines may need to be more inclusive for single
cases of breast cancer when the family structure is limited and probability models
need to be recreated using limited family history as an actual variable.
Imaging
Akin, O., S. Mironov, et al. (2007). "Imaging of uterine cancer." Radiol Clin North Am
45(1): 167-82.
Although surgical staging is the primary method of assessing prognostic factors
in endometrial cancer, cross-sectional imaging may help in treatment planning by
providing information about factors such as the depth of myometrial invasion,
cervical involvement, and nodal status. The pretreatment evaluation of cervical
cancer traditionally has consisted of clinical evaluation, laboratory tests, and
conventional radiographic studies, but more advanced imaging methods allow
additional insights into the morphologic and metabolic features of cervical cancer.
This article reviews the applications of modern imaging modalities in the
assessment of endometrial cancer and cervical cancer and their impact on
treatment planning and posttreatment follow-up.
Bartella, L., C. S. Smith, et al. (2007). "Imaging breast cancer." Radiol Clin North Am
45(1): 45-67.
Imaging has a significant role in diagnosing, treating, and monitoring breast
cancer. Advances in this field are having a great impact in the clinical
management of this disease. Breast cancer has now become an "outpatient
cancer". This article describes the role and advances of imaging in breast cancer.
Brooksby, B, BW Pogue, S Jiang, H Dehghani, S Srinivasan, C Kogel, TD Tosteson, J
Weaver, SP Poplack and KD Paulsen (2006). "Imaging breast adipose and
fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared
spectral tomography." Proc Natl Acad Sci U S A. 103(23): 8828-33.
Emerging Issues192
Magnetic resonance (MR)-guided near-infrared spectral tomography was
developed and used to image adipose and fibroglandular breast tissue of 11
normal female subjects, recruited under an institutional review board-approved
protocol. Images of hemoglobin, oxygen saturation, water fraction, and
subcellular scattering were reconstructed and show that fibroglandular fractions
of both blood and water are higher than in adipose tissue. Variation in adipose
and fibroglandular tissue composition between individuals was not significantly
different across the scattered and dense breast categories. Combined MR and
near-infrared tomography provides fundamental molecular information about
these tissue types with resolution governed by MR T1 images.
Carney, P. A., M. E. Goodrich, D. M. O'Mahony, A. N. Tosteson, M. S. Eliassen, S. P.
Poplack, S. Birnbaum, B. G. Harwood, K. A. Burgess, B. T. Berube, W. S. Wells, J. P.
Ball and M. M. Stevens (2000). "Mammography in New Hampshire: characteristics of
the women and the exams they receive." J Community Health 25(3): 183-98.
New Hampshire (NH) is one of two states that has developed a population-based
mammography registry. The purpose of this paper is to describe what we have
learned about mammography use in New Hampshire. After collecting data for 20
months, the database contains almost 110,000 mammographic encounters
representing 101,679 NH women, who range in age from 18 to 97 with a mean of
56.7 years (SD=10.91). Education levels are high with 92% having a high school
education and 59% with some college. Forty-six percent report their primary
insurance is private, 29% report HMO/PPO coverage, and 25% receive federal
health care assistance. Risk factors represented in the database include
(categories not mutually exclusive) advancing age (60% over age 50), hormone
replacement therapy use by menopausal women (40.6%), and a family history of
breast cancer (29%). Penetration of mammography relative to the NH population
is higher for younger age groups (40-48% for those aged 44-64) than older age
groups (34-39% for those aged 65-84). The majority of mammographic
encounters are routine screening exams (86%), often interpreted as negative or
normal with benign findings (88%). Use of comparison films to interpret either
diagnostic or screening mammography occurred in 86% of encounters. We have
matched 3,877 breast pathology records to these mammographic encounters.
The distribution of pathology outcomes for diagnostic exams was very similar to
that for screening exams (approximately 65% benign, 17% invasive breast
cancer, and 6% noninvasive breast cancer). Overall, we have designed a system
that is well accepted by the NH community. Challenges include careful
monitoring of data for coding errors, and a limitation of linking variables in
mammography and pathology data. Data represented in this registry are a critical
resource for research in mammographic screening and breast cancer early
detection.
Carney, P. A., M. E. Goodrich, et al. (2005). "Utilization of screening mammography in
New Hampshire: a population-based assessment." Cancer 104(8): 1726-32.
BACKGROUND: The objective of screening mammography is to identify breast
carcinoma early, which requires routine screening. Although self-report data
Emerging Issues193
indicate that screening utilization is high, the results of this population-based
assessment indicated that utilization is lower than reported previously.
METHODS: The authors compared New Hampshire population data from the
2000 Census with clinical encounter data for the corresponding time obtained
from the New Hampshire Mammography Network, a mammography registry that
captures approximately 90% of the mammograms performed in participating New
Hampshire facilities. RESULTS: The results showed that approximately 36% of
New Hampshire women either never had a mammogram or had not had a
mammogram in > 27 months (irregular screenees), and older women (80 yrs and
older) were less likely to be screened (79% unscreened/underscreened)
compared with younger women (ages 40-69 yrs; 28-32%
unscreened/underscreened). Of the screened women, 44% were adhering to an
interval of 14 months, and 21% were adhering within 15 months and 26 months.
The remaining 35% of the women had 1 or 2 mammograms and did not return
within 27 months. CONCLUSIONS: Routine mammography screening may be
occurring less often than believed when survey data alone are used. An
important, compelling concern is the reason women had one or two
mammograms only and then did not return for additional screening. This area
deserves additional research.
Carney, P. A., C. J. Kasales, A. N. Tosteson, J. E. Weiss, M. E. Goodrich, S. P.
Poplack, W. S. Wells and L. Titus-Ernstoff (2004). "Likelihood of additional work-up
among women undergoing routine screening mammography: the impact of age, breast
density, and hormone therapy use." Prev Med 39(1): 48-55.
BACKGROUND: Mammography screening can involve subsequent work-up to
determine a final screening outcome. Understanding the likelihood of different
events that follow initial screening is important if women and their health care
providers are to be accurately informed about the screening process.
METHODS: We conducted an analysis of additional work-up following screening
mammography to characterize use of supplemental imaging and
recommendations for biopsy and/or surgical consultation and the factors
associated with their use. We included all events following screening
mammography performed between 1/1/1998 and 12/31/1999 on a populationbased sample of 37,632 New Hampshire women. We calculated adjusted odds
ratios (OR) and 95% confidence intervals (CI) for supplemental imaging and
recommended biopsy and/or surgical consultation as function of age,
menopausal status and HRT use, breast density, and family history of breast
cancer. RESULTS: Ninety-one percent of women (n = 34,445) did not require
supplemental imaging. Among those who did (n = 3187), 84% had additional
views, 9% ultrasound, and 7% received both. Supplemental imaging was
affected by age (OR 0.84; 95% CI = 0.76-0.94 for 50-59; OR = 0.66; 95% CI =
0.58-0.75 for > or = 60 versus < 50), menopausal status, and HRT use (OR =
1.33; 95% CI = 1.21-1.47 for peri- or post-menopausal HRT users; OR = 1.14;
95% CI = 1.01-1.29 for premenopausal versus peri- or post-menopausal nonHRT users), breast density (OR = 1.43; 95% CI = 1.33-1.55 for dense versus
fatty breasts) and family history (OR = 1.15; 95% CI = 1.06-1.25 for any versus
Emerging Issues194
none). In women with supplemental imaging, age (OR = 1.80; 95% CI = 1.112.90 for > or = 60, relative to <50) and imaging type (OR = 3.23; 95% CI = 2.384.38 for ultrasound with or without additional views versus additional views only)
were significantly associated with biopsy and/or surgical consultation
recommendation. In those with no supplemental imaging, breast density was
associated with recommended biopsy and/or surgical consultation (OR = 1.53;
95% CI = 1.13-2.07 for dense versus fatty breasts). CONCLUSIONS: Breast
density and HRT use are both independent predictors of use of supplemental
imaging in women. With advancing age (age 60 and older), women were less
likely to require follow-up imaging but more likely to receive a recommendation
for biopsy and/or surgical consultation. This information should be used to inform
women about the likelihood of services received as part of the screening workup.
Carney, P. A., C. J. Kasales, et al. (2004). "Likelihood of additional work-up among
women undergoing routine screening mammography: the impact of age, breast density,
and hormone therapy use." Prev Med 39(1): 48-55.
BACKGROUND: Mammography screening can involve subsequent work-up to
determine a final screening outcome. Understanding the likelihood of different
events that follow initial screening is important if women and their health care
providers are to be accurately informed about the screening process.
METHODS: We conducted an analysis of additional work-up following screening
mammography to characterize use of supplemental imaging and
recommendations for biopsy and/or surgical consultation and the factors
associated with their use. We included all events following screening
mammography performed between 1/1/1998 and 12/31/1999 on a populationbased sample of 37,632 New Hampshire women. We calculated adjusted odds
ratios (OR) and 95% confidence intervals (CI) for supplemental imaging and
recommended biopsy and/or surgical consultation as function of age,
menopausal status and HRT use, breast density, and family history of breast
cancer. RESULTS: Ninety-one percent of women (n = 34,445) did not require
supplemental imaging. Among those who did (n = 3187), 84% had additional
views, 9% ultrasound, and 7% received both. Supplemental imaging was
affected by age (OR 0.84; 95% CI = 0.76-0.94 for 50-59; OR = 0.66; 95% CI =
0.58-0.75 for > or = 60 versus < 50), menopausal status, and HRT use (OR =
1.33; 95% CI = 1.21-1.47 for peri- or post-menopausal HRT users; OR = 1.14;
95% CI = 1.01-1.29 for premenopausal versus peri- or post-menopausal nonHRT users), breast density (OR = 1.43; 95% CI = 1.33-1.55 for dense versus
fatty breasts) and family history (OR = 1.15; 95% CI = 1.06-1.25 for any versus
none). In women with supplemental imaging, age (OR = 1.80; 95% CI = 1.112.90 for > or = 60, relative to <50) and imaging type (OR = 3.23; 95% CI = 2.384.38 for ultrasound with or without additional views versus additional views only)
were significantly associated with biopsy and/or surgical consultation
recommendation. In those with no supplemental imaging, breast density was
associated with recommended biopsy and/or surgical consultation (OR = 1.53;
95% CI = 1.13-2.07 for dense versus fatty breasts). CONCLUSIONS: Breast
Emerging Issues195
density and HRT use are both independent predictors of use of supplemental
imaging in women. With advancing age (age 60 and older), women were less
likely to require follow-up imaging but more likely to receive a recommendation
for biopsy and/or surgical consultation. This information should be used to inform
women about the likelihood of services received as part of the screening workup.
Carney, P. A., D. L. Miglioretti, et al. (2003). "Individual and combined effects of age,
breast density, and hormone replacement therapy use on the accuracy of screening
mammography." Ann Intern Med 138(3): 168-75.
BACKGROUND: The relationships among breast density, age, and use of
hormone replacement therapy (HRT) in breast cancer detection have not been
fully evaluated. OBJECTIVE: To determine how breast density, age, and use of
HRT individually and in combination affect the accuracy of screening
mammography. DESIGN: Prospective cohort study. SETTING: 7 populationbased mammography registries in North Carolina; New Mexico; New Hampshire;
Vermont; Colorado; Seattle, Washington; and San Francisco, California.
PARTICIPANTS: 329 495 women 40 to 89 years of age who had 463 372
screening mammograms from 1996 to 1998; 2223 women received a diagnosis
of breast cancer. MEASUREMENTS: Breast density, age, HRT use, rate of
breast cancer occurrence, and sensitivity and specificity of screening
mammography. RESULTS: Adjusted sensitivity ranged from 62.9% in women
with extremely dense breasts to 87.0% in women with almost entirely fatty
breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44
years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity
increased from 89.1% in women with extremely dense breasts to 96.9% in
women with almost entirely fatty breasts. In women who did not use HRT,
adjusted specificity increased from 91.4% in women 40 to 44 years of age to
94.4% in women 80 to 89 years of age. In women who used HRT, adjusted
specificity was about 91.7% for all ages. CONCLUSIONS: Mammographic breast
density and age are important predictors of the accuracy of screening
mammography. Although HRT use is not an independent predictor of accuracy, it
probably affects accuracy by increasing breast density.
Carpenter, C. M., B. W. Pogue, et al. (2007). "Image-guided optical spectroscopy
provides molecular-specific information in vivo: MRI-guided spectroscopy of breast
cancer hemoglobin, water, and scatterer size." Opt Lett 32(8): 933-5.
A multimodality instrument that integrated optical or near-infrared spectroscopy
into a magnetic resonance imaging (MRI) breast coil was used to perform a pilot
study of image-guided spectroscopy on cancerous breast tissue. These results
are believed to be the first multiwavelength spectroscopic images of breast
cancer using MRI-guided constraints, and they show the cancer tumor to have
high hemoglobin and water values, decreased oxygen saturation, and increased
subcellular granularity. The use of frequency-domain diffuse tomography
methods at many wavelengths provides the spectroscopy required for recovering
maps of absorbers and scattering spectra, but the integration with MRI allows
Emerging Issues196
these data to be recovered on an image field that preserves high resolution and
fuses the two data sets together. Integration of molecular spectroscopy into
standard clinical MRI can be achieved with this approach to spectral tomography.
D'Orsi, C., S. P. Tu, et al. (2005). "Current realities of delivering mammography services
in the community: do challenges with staffing and scheduling exist?" Radiology 235(2):
391-5.
PURPOSE: To evaluate the current (2001-2002) capacity of community-based
mammography facilities to deliver screening and diagnostic services in the
United States. MATERIALS AND METHODS: Institutional review board
approvals and patient consent were obtained. A mailed survey was sent to 53
eligible mammography facilities in three states (Washington, New Hampshire,
and Colorado). Survey questions assessed equipment and staffing availability, as
well as appointment waiting times for screening and diagnostic mammography
services. Criterion-related content and construct validity were obtained first by
means of a national advisory committee of academic, scientific, and clinical
colleagues in mammography that reviewed literature on existing surveys and
second by pilot testing a series of draft surveys among community
mammography facilities not inclusive of the study facilities. The final survey
results were independently double entered into a relational database with
programmed data checks. The data were sent encrypted by means of file
transfer protocol to a central analytical center at Group Health Cooperative. A
two-sided P value with alpha = .05 was considered to show statistical
significance in all analyses. RESULTS: Forty-five of 53 eligible mammography
facilities (85%) returned the survey. Shortages of radiologists relative to the
mammographic volume were found in 44% of mammography facilities overall,
with shortages of radiologists higher in not-for-profit versus for-profit facilities
(60% vs 28% reported). Shortages of Mammography Quality Standards Actqualified technologists were reported by 20% of facilities, with 46% reporting
some level of difficulty in maintaining qualified technologists. Waiting times for
diagnostic mammography ranged from less than 1 week to 4 weeks, with 85%
performed within 1 week. Waiting times for screening mammography ranged
from less than 1 week to 8 weeks, with 59% performed between 1 week and 4
weeks. Waiting times for both diagnostic and screening services were two to
three times higher in high-volume compared with low-volume facilities.
CONCLUSION: Survey results show shortages of radiologists and certified
mammography technologists.
Egger, J. R., G. R. Cutter, et al. (2005). "Mammographers' perception of women's
breast cancer risk." Med Decis Making 25(3): 283-9.
OBJECTIVE: To understand mammographers' perception of individual women's
breast cancer risk. MATERIALS AND METHODS: Radiologists interpreting
screening mammography examinations completed a mailed survey consisting of
questions pertaining to demographic and clinical practice characteristics, as well
as 2 vignettes describing different risk profiles of women. Respondents were
asked to estimate the probability of a breast cancer diagnosis in the next 5 years
Emerging Issues197
for each vignette. Vignette responses were plotted against mean recall rates in
actual clinical practice. RESULTS: The survey was returned by 77% of eligible
radiologists. Ninety-three percent of radiologists overestimated risk in the
vignette involving a 70-year-old woman; 96% overestimated risk in the vignette
involving a 41-year-old woman. Radiologists who more accurately estimated
breast cancer risk were younger, worked full-time, were affiliated with an
academic medical center, had fellowship training, had fewer than 10 years
experience interpreting mammograms, and worked more than 40% of the time in
breast imaging. However, only age was statistically significant. No association
was found between radiologists' risk estimate and their recall rate.
CONCLUSION: U.S. radiologists have a heightened perception of breast cancer
risk.
Elmore, J. G., S. H. Taplin, et al. (2005). "Does litigation influence medical practice?
The influence of community radiologists' medical malpractice perceptions and
experience on screening mammography." Radiology 236(1): 37-46.
PURPOSE: To assess the relationship between radiologists' perception of and
experience with medical malpractice and their patient-recall rates in actual
community-based clinical settings. MATERIALS AND METHODS: All study
activities were approved by the institutional review boards of the involved
institutions, and patient and radiologist informed consent was obtained where
necessary. This study was performed in three regions of the United States
(Washington, Colorado, and New Hampshire). Radiologists who routinely
interpret mammograms completed a mailed survey that included questions on
demographic data, practice environment, and medical malpractice. Survey
responses were linked to interpretive performance for all screening
mammography examinations performed between January 1, 1996, and
December 31, 2001. The odds of recall were modeled by using logistic
regression analysis based on generalized estimating equations that adjust for
study region. RESULTS: Of 181 eligible radiologists, 139 (76.8%) returned the
survey with full consent. The analysis included 124 radiologists who had
interpreted a total of 557 143 screening mammograms. Approximately half (64 of
122 [52.4%]) of the radiologists reported a prior malpractice claim, with 18
(14.8%) reporting mammography-related claims. The majority (n = 51 [81.0%]) of
the 63 radiologists who responded to a question regarding the degree of stress
caused by a medical malpractice claim described the experience as very or
extremely stressful. More than three of every four radiologists (ie, 94 [76.4%] of
123) expressed concern about the impact medical malpractice has on
mammography practice, with over half (72 [58.5%] of 123) indicating that their
concern moderately to greatly increased the number of their recommendations
for breast biopsies. Radiologists' estimates of their future malpractice risk were
substantially higher than the actual historical risk. Almost one of every three
radiologists (43 of 122 [35.3%]) had considered withdrawing from mammogram
interpretation because of malpractice concerns. No significant association was
found between recall rates and radiologists' experiences or perceptions of
medical malpractice. CONCLUSION: U.S. radiologists are extremely concerned
Emerging Issues198
about medical malpractice and report that this concern affects their recall rates
and biopsy recommendations. However, medical malpractice experience and
concerns were not associated with recall or false-positive rates. Heightened
concern of almost all radiologists may be a key reason that recall rates are higher
in the United States than in other countries, but this hypothesis requires further
study.
Emro, Robert (2004) UNH chemists invent molecules for cancer imaging: “Clamshell”
could allow earlier tumor detection with PET scans UNH College of Engineering and
Physical Sciences Volume, DOI:
Two University of New Hampshire professors, in collaboration with a Washington
University colleague, have synthesized and studied novel molecules which have
the potential to save lives by enabling doctors to spot cancer earlier.
Fenton, J. J., J. Egger, et al. (2006). "Reality check: perceived versus actual
performance of community mammographers." AJR Am J Roentgenol 187(1): 42-6.
OBJECTIVE: Federal regulations mandate that radiologists receive regular albeit
limited feedback regarding their interpretive accuracy in mammography. We
sought to determine whether radiologists who regularly receive more extensive
feedback can report their actual performance in screening mammography
accurately. SUBJECTS AND METHODS: Radiologists (n = 105) who routinely
interpret screening mammograms in three states (Washington, Colorado, and
New Hampshire) completed a mailed survey in 2001. Radiologists were asked to
estimate how frequently they recommended additional diagnostic testing after
screening mammography and the positive predictive value of their
recommendations for biopsy (PPV2). We then used outcomes from 336,128
screening mammography examinations interpreted by the radiologists from 1998
to 2001 to ascertain their true rates of recommendations for diagnostic testing
and PPV2. RESULTS: Radiologists' self-reported rate of recommending
immediate additional imaging (11.1%) exceeded their actual rate (9.1%) (mean
difference, 1.9%; 95% confidence interval [CI], 0.9-3.0%). The mean selfreported rate of recommending short-interval follow-up was 6.2%; the true rate
was 1.8% (mean difference, 4.3%; 95% CI, 3.6-5.1%). Similarly, the mean selfreported and true rates of recommending immediate biopsy or surgical evaluation
were 3.2% and 0.6%, respectively (mean difference, 2.6%; 95% CI, 1.8-3.4%).
Conversely, radiologists' mean self-reported PPV2 (18.3%) was significantly less
than their mean true PPV2 (27.6%) (mean difference, -9.3%; 95% CI, -12.4% to 6.2%). CONCLUSION: Despite regular performance feedback, community
radiologists may overestimate their true rates of recommending further evaluation
after screening mammography and underestimate their true positive predictive
value.
Hendrick, R. E., G. R. Cutter, et al. (2005). "Community-based mammography practice:
services, charges, and interpretation methods." AJR Am J Roentgenol 184(2): 433-8.
OBJECTIVE: The purpose of our study was to accurately describe facility
characteristics among community-based screening and diagnostic
Emerging Issues199
mammography practices in the United States. MATERIALS AND METHODS: A
survey was developed and applied to community-based facilities providing
screening mammography in three geographically distinct locations in the states
of Washington, Colorado, and New Hampshire. The facility survey was
conducted between December 2001 and September 2002. Characteristics
surveyed included facility type, services offered, charges for screening and
diagnostic mammography, information systems, and interpretation methods,
including the frequency of double interpretation. RESULTS: Among 45
responding facilities, services offered included screening mammography at all
facilities, diagnostic mammography at 34 facilities (76%), breast sonography at
30 (67%), breast MRI at seven (16%), and nuclear medicine breast scanning at
seven (16%). Most facilities surveyed were radiology practices in nonhospital
settings. Eight facilities (18%) reported performing clinical breast examinations
routinely along with screening mammography. Only five screening sites (11%)
used computer-aided detection (CAD) and only two (5%) used digital
mammography. Nearly two thirds of facilities interpreted screening
mammography examinations on-site, whereas 91% of facilities interpreted
diagnostic examinations on-site. Only three facilities (7%) interpreted screening
examinations on line as they were performed. Approximately half of facilities
reported using some type of double interpretation, although the methods of
double interpretation and the fraction of cases double-interpreted varied widely
across facilities. On average, approximately 15% of screening examinations and
10% of diagnostic examinations were reported as being double-interpreted.
CONCLUSION: Comparison of this survey's results with those collected a
decade earlier indicates dramatic changes in the practice of mammography,
including a clear distinction between screening and diagnostic mammography,
batch interpretation of screening mammograms, and improved quality assurance
and medical audit tools. Diffusion of new technologies such as CAD and digital
mammography was not widespread. The methods of double-interpretation and
the fraction of cases double-interpreted varied widely across study sites.
Jefford, M. (2006). "Factors associated with interval adherence to mammography
screening in a population-based sample of New Hampshire women." Cancer 106(9):
2084-5; author reply 2085.
Li, D., P. M. Meaney, et al. (2003). "Comparisons of three alternative breast modalities
in a common phantom imaging experiment." Med Phys 30(8): 2194-205.
Four model-based imaging systems are currently being developed for breast
cancer detection at Dartmouth College. A potential advantage of multimodality
imaging is the prospect of combining information collected from each system to
provide a more complete diagnostic tool that covers the full range of the patient
and pathology spectra. In this paper it is shown through common phantom
experiments on three of these imaging systems that it was possible to correlate
different types of image information to potentially improve the reliability of tumor
detection. Imaging experiments were conducted with common phantoms which
mimic both dielectric and optical properties of the human breast. Cross modality
Emerging Issues200
comparison was investigated through a statistical study based on the repeated
data sets of reconstructed parameters for each modality. The system standard
error between all methods was generally less than 10% and the correlation
coefficient across modalities ranged from 0.68 to 0.91. Future work includes the
minimization of bias (artifacts) on the periphery of electrical impedance
spectroscopy images to improve cross modality correlation and implementation
of the multimodality diagnosis for breast cancer detection.
Meaney, P., M. Fanning, et al. (2007). "Initial clinical experience with microwave breast
imaging in women with normal mammography." Acad Radiol 14(2): 207-218.
RATIONALE AND OBJECTIVES: We have developed a microwave tomography
system for experimental breast imaging. MATERIALS AND METHODS: In this
article, we illustrate a strategy for optimizing the coupling liquid for the antenna
array based on in vivo measurement data. We present representative phantom
experiments to illustrate the imaging system's ability to recover accurate property
distributions over the range of dielectric properties expected to be encountered
clinically. To demonstrate clinical feasibility and assess the microwave properties
of the normal breast in vivo, we summarize our initial experience with microwave
breast exams of 43 women with negative mammography according to the Breast
Imaging Reporting and Data System (BI-RADS 1). RESULTS: The clinical results
show a high degree of bilateral symmetry in the whole breast average microwave
properties. Focal assessments of microwave properties are associated with
breast tissue composition evaluated through radiographic density categorization
verified through magnetic resonance image correlation in selected cases.
Specifically, both whole-breast average and local microwave properties increase
with increasing radiographic density, in which the latter exhibits a more
substantial rise. CONCLUSION: These findings support our hypothesis that
water content variations in the breast play an influential role in dictating the
overall dielectric property distributions and indicate that the microwave properties
in the breast are more heterogeneous than previously believed based on ex vivo
property measurements reported in the literature.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Knowing Risk Factors and Imaging. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
An example of why this is relevant is the American Cancer Society (ACS) new
Magnetic Resonance Imaging (MRI) recommendation. ACS recently
recommended magnetic resonance imaging, in addition to mammograms, for
very high risk women. Unfortunately, most women do not know what risk
category they are in, nor is it a simple matter to define risk since there are
several risk models available for doctors and patients to use. Most women who
are diagnosed with breast cancer have none of the known risk factors. See the
ACS web site:
http://www.cancer.org/docroot/MED/content/MED_2_1x_American_Cancer_Soci
ety_Issues_Recommendation_on_MRI_for_Breast_Cancer_Screening.asp
Emerging Issues201
In response to these new MRI guidelines, the National Breast Cancer Coalition Fund
(NBCCF) noted the lack of standards for equipment and MRI reader competency
as well as the high cost. NBCCF is concerned because none of the clinical
studies on which the ACS recommendation is based was a randomized
controlled trial, the generally accepted standard as the basis for a conclusive
result. There is also a lack of data on whether MRI screening decreases breast
cancer mortality, an important goal for a screening program. If MRI availability
and use becomes widespread, NBCCF points out it is unlikely that randomized
clinical trials will ever be conducted to assess its effect on mortality.
Sprague, Jennifer E., Yijie Peng, Xiankai Sun, Gary R. Weisman, Edward H. Wong,
Samuel Achilefu and Carolyn J. Anderson (2004). "Preparation and Biological
Evaluation of Copper-64–Labeled Tyr3-Octreotate Using a Cross-Bridged Macrocyclic
Chelator " Clinical Cancer Research 10: 8674-8682.
Purpose: Somatostatin receptors (SSTr) are expressed on many neuroendocrine
tumors, and several radiotracers have been developed for imaging these types of
tumors. For this reason, peptide analogues of somatostatin have been well
characterized. Copper-64 (t1/2 = 12.7 hours), a positron emitter suitable for
positron emission tomography (PET) imaging, was shown recently to have
improved in vivo clearance properties when chelated by the cross-bridged
tetraazamacrocycle 4,11-bis(carboxymethyl)-1,4,8,11tetraazabicyclo(6.6.2)hexadecane (CB-TE2A) compared with 1,4,8,11tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA).
Experimental Design: CB-TE2A and TETA were conjugated to the somatostatin
analogue tyrosine-3-octreotate (Y3-TATE) for evaluation of CB-TE2A as a
bifunctional chelator of 64Cu. The in vitro affinity of each compound for SSTr was
determined using a homologous competitive binding assay. In vivo
characteristics of both radiolabeled compounds were examined in biodistribution
and microPET studies of AR42J tumor-bearing rats.
Results: Cu-CB-TE2A-Y3-TATE (Kd = 1.7 nmol/L) and Cu-TETA-Y3-TATE (Kd = 0.7
nmol/L) showed similar affinities for AR42J derived SSTr. In biodistribution
studies, nonspecific uptake in blood and liver was lower for 64Cu-CB-TE2A-Y3TATE. Differences increased with time such that, at 4 hours, blood uptake was
4.3-fold higher and liver uptake was 2.4-fold higher for 64Cu-TETA-Y3-TATE
than for 64Cu-CB-TE2A-Y3-TATE. In addition, 4.4-times greater tumor uptake
was detected with 64Cu-CB-TE2A-Y3-TATE than with 64Cu-TETA-Y3-TATE at 4
hours postinjection. MicroPET imaging yielded similar results.
Conclusions: CB-TE2A appears to be a superior in vivo bifunctional chelator of 64Cu for
use in molecular imaging by PET or targeted radiotherapy due to both improved
nontarget organ clearance and higher target organ uptake of 64Cu-CB-TE2A-Y3TATE compared with 64Cu-TETA-Y3-TATE.
Prostate Cancer Screening
Emerging Issues202
American Urologic Association. "Prostate Cancer Checklist." Retrieved July 1, 2007,
from http://www.healthcentral.com/prostate/prostate-check-3075-143.html.
This is a short survey that a man can take to determine if he needs to be
screened for prostate cancer.
Bangma, CH, S Roemeling and FH Schröder (2007, March). "Overdiagnosis and
overtreatment of early detected prostate cancer." World Journal of Urology 25(1): 3-9.
Early detection of prostate cancer is associated with the diagnosis of a
considerable proportion of cancers that are indolent, and that will hardly ever
become symptomatic during lifetime. Such overdiagnosis should be avoided in all
forms of screening because of potential adverse psychological and somatic side
effects. The main threat of overdiagnosis is overtreatment of indolent disease.
Men with prostate cancer that is likely to be indolent may be offered active
surveillance. Evaluation of active surveillance studies and validation of new
biological parameters for risk assessment are expected.
Centers for Disease Control. (2007). "2007 prostate data." from
http://www.cdc.gov/cancer/prostate/prospdf/0607_prostate_fs.pdf.
This PDF from the CDC has recent data on prostate cancer like risk factors- age,
race, and family history as well as prevention/risk- herbal supplements, good
diets(prevention), vitamin E, poor diets (risk), hormones, environment, obesity.
Also has screening info DRE, and PSA test.
Chuang AY, Chang SJ, Horng CF, Tsou MH. (2007- May). "Study of prostate cancer
pathologic features in Chinese populations." Urology 69(5): 915-920.
OBJECTIVES: To report the pathologic features of prostate cancer and its
clinical outcome in the Chinese population in Taiwan. METHODS: A total of 139
radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen
Cancer Center from 1993 to 2001 were reviewed. RESULTS: The median patient
age was 69 years. The histologic type was acinar adenocarcinoma in 137,
mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median
tumor number in each prostate gland was 2. The main tumor location was
distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%).
The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in
48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle
invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of
the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19
(13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P
= 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL
versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012),
seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001)
were all significant factors for disease progression on univariate analysis. On
multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10
ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin
status (P = 0.02) remained significant. CONCLUSIONS: The patients with
prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center
Emerging Issues203
were older and had greater PSA levels, a more advanced stage, higher grade
tumors, and high positive surgical margin rates. Increased public awareness and
implementing a PSA screening program in Taiwan are of crucial importance.
Frydenberg M, Wijesinha S. (May 2007). "Diagnosing prostate cancer - what GPs need
to know." Austrailian Family Physician 36(5): 345-347.
BACKGROUND: The symptoms and signs of prostate cancer usually manifest
after it is too late to 'cure' the condition. General practitioners are ideally suited to
diagnose this disease early and need to know the latest information about how
best to identify and advise patients. OBJECTIVE: This article describes the latest
information about the natural history and detection of one of the commonest
cancers in Australian men. DISCUSSION: Prostate cancer rarely causes
symptoms in the early stage and lower urinary tract symptoms (LUTS) are more
likely to be due to benign prostate disease rather than cancer. Identifying
asymptomatic prostate cancer requires both prostate specific antigen (PSA) and
digital rectal examination as about one-fifth of men with prostate cancer have a
'normal' PSA. Although on currently available evidence population screening
cannot be recommended, 'case detection' in men deemed to be at risk of
prostate cancer is widely practised. Informed patient participation in this process
is vital.
Gennari R, Veronesi U, Andreoli C, Betka J, Castelli A, Gatti G, Hugosson J, Llovet JM,
Melia J, Nakhosteen JA, Pastorino U, Sideri M, Stephan C, Veronesi P, Zurrida S.
(2007). "Early detection of cancer: ideas for a debate." critical reviews in
oncology/hematology 61(2): 97-103.
Even if the overall number of cancer is increasing, the mortality has started to
decrease in the Western World. The role of early detection in this decrease is a
matter of debate. To assess its impact on mortality it is important to distinguish
between diagnosis of cancer in symptomatic patients, and early detection in
asymptomatic individuals who may self-refer or who may be offered ad hoc or
systematic screening. The policies for early detection and screening vary greatly
between European countries, despite many similarities in their cancer burden,
and this partly reflects the uncertainties surrounding asymptomatic testing for
cancer. A Task Force of European expert, held in Azzate (VA), Italy, established
to address these issues, acknowledged the need for more research in the field of
individual risk assessment since general statistics are more and more perceived
as inadequate to design personal early detection plans. The group also
recognised that combinations of early detection and screening will enforce the
effectiveness of new treatments in curbing mortality curves, although policies will
vary with different cancers.
Graif T, Loeb S, Roehl KA, Gashti SN, Griffin C, Yu X, Catalona WJ. (2007). "Under
diagnosis and over diagnosis of prostate cancer." journal of Urology 178(1): 88-92.
PURPOSE: We quantified the rates of over and under diagnosis of prostate
cancer in 2 large patient cohorts during the last 15 years. MATERIALS AND
METHODS: A total of 2,126 men with clinical stage T1c prostate cancer were
Emerging Issues204
treated with radical prostatectomy during 1 of the 3 periods 1989 to 1995, 1995
to 2001 and 2001 to 2005. The respective proportions of men with a tumor that
met our criteria for over diagnosis (0.5 cm3 or less, confined to the prostate with
clear surgical margins and no Gleason pattern 4 or 5) and under diagnosis
(nonorgan confined, pathological stage T3 or greater, or positive surgical
margins) were examined. RESULTS: The proportion of men with an over
diagnosed tumor was 1.3% to 7.1%. The proportion with prostate cancer that
was under diagnosed was 25% to 30%. An ancillary finding was that decreasing
the prostate specific antigen threshold for biopsy from 4.0 to 2.5 ng/ml in the
screened population resulted in a lower rate of under diagnosis from 30% to
26%, a higher rate of over diagnosis from 1.3% to 7.1% and an increase in the 5year progression-free survival rate from 85% to 92%. Men who were 55 years or
younger were significantly more likely to meet our criteria for over diagnosed
cancer. CONCLUSIONS: Under diagnosis of prostate cancer continues to occur
more frequently than over diagnosis. Lowering the prostate specific antigen
threshold for recommending biopsy to 2.5 ng/ml resulted in a lower rate of under
diagnosis and a higher progression-free survival rate.
Greco, K. (2006). "Cancer screening in older adults in an era of genomics and
longevity." Seminars in Oncology Nursing 22(1): 10-19.
OBJECTIVES: To provide an overview of cancer genomics and cancer screening
in older adults with a focus on breast, prostate, and colon cancers. DATA
SOURCES: Journal articles, research articles, and web sites. CONCLUSION:
Cancer screening in older populations is often in the context of one or more comorbid conditions, cancer survivorship, genomic information, and competing
health priorities. The field of cancer screening has outgrown the tools available to
enable health care providers and older adults to make informed cancer screening
decisions. Research is needed to develop clinical screening tools that integrate
age, cancer risk, life expectancy, and comorbidity. IMPLICATIONS FOR
NURSING PRACTICE: Health care providers are faced with opportunities and
challenges in the prevention and early detection of cancer in older Americans.
Guerra CE, Jacobs SE, Holmes JH, Shea JA. (2007). "Are physicians discussing
prostate cancer screening with their patients and why or why not? A pilot study." journal
of general medicine 22(7): 901-7.
BACKGROUND: Prostate cancer screening (PCS) is controversial. Ideally,
patients should understand the risks and benefits of screening before undergoing
PSA testing. This study assessed whether primary care physicians routinely
discuss PCS and explored the barriers to and facilitators of these discussions.
METHODS: Qualitative pilot study involving in-depth, semistructured interviews
with 18 purposively sampled, academic and community-based primary care
physicians. Barriers and facilitators of PCS discussions were ascertained using
both interviews and chart-stimulated recall--a technique utilizing patient charts to
probe recall and provide context to physician decision-making during clinic
encounters. Analysis was performed using consensus conferences based on
grounded theory techniques. RESULTS: All 18 participating physicians reported
Emerging Issues205
that they generally discussed PCS with patients, though 6 reported sometimes
ordering PSA tests without discussion. A PCS discussion occurred in only 16
(36%) of the 44 patient-physician encounters when patients were due for PCS
that also met criteria for chart-stimulated recall. Barriers to PCS discussion were
patient comorbidity, limited education/health literacy, prior refusal of care,
physician forgetfulness, acute-care visits, and lack of time. Facilitators of PCS
discussion included patient-requested screening, highly educated patients, family
history of prostate cancer, African-American race, visits for routine physicals,
review of previous PSA results, extra time during encounters, and reminder
systems. CONCLUSIONS: PCS discussions sometimes do not occur. Important
barriers to discussion are inadequate time for health maintenance, physician
forgetfulness, and patient characteristics. Future research should explore using
educational and decision support interventions to involve more patients in PCS
decisions.
Hoffman RM, Denberg T, Hunt WC, Hamilton AS. (2007). "Prostate Cancer Testing
following a Negative Prostate Biopsy: Over Testing the Elderly." Journal of Gene
Medicine ahead of print.
BACKGROUND: Screening elderly men for prostate cancer is not recommended
because definitive treatments are unlikely to extend life expectancy.
OBJECTIVE: Describe clinical outcomes after a negative prostate biopsy in a
population-based cohort of men ages 65 and older. DESIGN: Retrospective
cohort study. PARTICIPANTS: 9,410 Medicare-eligible men who underwent a
prostate biopsy in Los Angeles or New Mexico in 1992. MEASUREMENTS: We
used Medicare and SEER databases to identify a cohort with an initial negative
biopsy (n = 7,119) and to ascertain survival, subsequent PSA testing, prostate
biopsies, and prostate cancer detection and treatment through 1997. RESULTS:
The overall 5-year survival was 79.4% (95% CI 78.4-80.3), but only 74.6% (72.476.7) for men ages 75-79 at the time of the initial negative biopsy and 55.0%
(51.9-57.9) for men ages 80+. During a median 4.5 years follow-up, a cumulative
75.0% (73.9-76.1) of the cohort underwent PSA testing. Among men ages 75-79
and 80+, the cumulative proportions that underwent PSA testing were 75.4%
(73.0-77.8) and 74.3% (71.1-77.5), respectively. Additionally, 29.1% (26.7-31.6)
of men ages 75-79 and 20.1% (17.6-23.1) of men ages 80+ underwent repeat
prostate biopsy, and 10.9% (9.4-12.7) and 8.3% (6.6-10.4), respectively, were
diagnosed with cancer. Among men ages 75+ with localized cancers,
approximately 34% received definitive treatment. CONCLUSIONS: High
proportions of men ages 75+ underwent PSA testing and repeat prostate
biopsies after an initial negative prostate biopsy. Given the known harms and
uncertain benefits for finding and treating localized cancer in elderly men, most
continued PSA testing after a negative biopsy is potentially inappropriate.
Hughes Halbert C, Barg FK, Weathers B, Delmoor E, Coyne J, Wileyto EP, Arocho J,
Mahler B, Malkowicz SB. (2007). "Differences in cultural beliefs and values among
African American and European American men with prostate cancer." Cancer Control
14(3): 277-284.
Emerging Issues206
BACKGROUND: Although cultural values are increasingly being recognized as
important determinants of psychological and behavioral outcomes following
cancer diagnosis and treatment, empirical data are not available on cultural
values among men. This study evaluated differences in cultural values related to
religiosity, temporal orientation, and collectivism among African American and
European American men. METHODS: Participants were 119 African American
and European American men who were newly diagnosed with early-stage and
locally advanced prostate cancer. Cultural values were evaluated by self-report
using standardized instruments during a structured telephone interview.
RESULTS: After controlling for sociodemographic characteristics, African
American men reported significantly greater levels of religiosity (Beta = 24.44, P
less than .001) compared with European American men. African American men
(Beta = 6.30, P less than .01) also reported significantly greater levels of future
temporal orientation. In addition, men with more aggressive disease (eg, higher
Gleason scores) (Beta = 5.11, P less than .01) and those who were pending
treatment (Beta = -6.42, P less than .01) reported significantly greater levels of
future temporal orientation. CONCLUSIONS: These findings demonstrate that
while ethnicity is associated with some cultural values, clinical experiences with
prostate cancer may also be important. This underscores the importance of
evaluating the effects of both ethnicity and clinical factors in research on the
influence of cultural values on cancer prevention and control.
Katz DA, Jarrard DF, McHorney CA, Hillis SL, Wiebe DA, Fryback DG. (2007). "Health
perceptions in patients who undergo screening and workup for prostate cancer."
Urology 69(2): 215-220.
OBJECTIVES: False-positive screening tests may induce persistent
psychological distress. This study was designed to determine whether a positive
screening test with negative biopsy findings for prostate cancer is associated with
worsened mental health during short-term follow-up. METHODS: We conducted
a cross-sectional telephone survey of two groups of men approximately 2 months
after testing: group 1, 109 men with an abnormal prostate-specific antigen level
or digital rectal examination findings but with negative biopsy findings for prostate
cancer; and group 2, 101 age-matched primary care patients with PSA screening
levels in the reference range (less than 4 ng/mL). Primary outcomes included
state anxiety and prostate cancer-related worry. Secondary outcomes included
Medical Outcomes Study Short Form 36-item Health Survey subscales and
sexual function items. Multivariate regression techniques were used to adjust for
differences in baseline covariates. RESULTS: Group 1 patients were more
worried than group 2 patients about getting prostate cancer (mean worry 3.9
versus 4.5, P = 0.0001, using a 5-point scale, with 1 indicating extreme worry and
5 no worry). Group 1 patients also perceived their risk of prostate cancer to be
significantly greater than that of controls (P = 0.001). No significant differences
were found across state anxiety or Medical Outcomes Study Short Form 36-item
Health Survey subscales. Sexual bother was greater for group 1 patients, with
19% reporting that sexual function was a moderate to big problem compared with
10% of group 2 patients (P = 0.0001). CONCLUSIONS: Men with abnormal
Emerging Issues207
prostate cancer screening tests report increased cancer-related worry and more
problems with sexual function, despite having a negative biopsy result. Effective
counseling interventions are needed before prostate cancer screening and during
follow-up.
Keefe, Diane. (2007). "Study Identifies characteristics of clinicians likely to order
inappropriate prostate screenings." from http://www.eurekalert.org/pub_releases/200707/jaaj-sic070507.php.
Provides information on the type of doctors that are ordering unnessary
screenings- for example in young men, or older men who have a short life
expectancy: Practitioners who were urology specialists, male, infrequent PSA
tests orderers and affiliated with specific hospitals had significantly higher levels
of inappropriate PSA screening. Compared with attending physicians, nurses and
physician assistants had significantly lower levels of inappropriate screening,” the
authors write.
Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, Dixon LB, Urban DA,
Crawford ED, Hayes RB. (2006). "A prospective study of lycopene and tomato product
intake and risk of prostate cancer." Cancer Epidemiology and Biomarkers & Prevention
15(1): 92-98.
BACKGROUND: Dietary lycopene and tomato products may reduce risk of
prostate cancer; however, uncertainty remains about this possible
association.METHODS: We evaluated the association between intake of
lycopene and specific tomato products and prostate cancer risk in the Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study
designed to investigate cancer early detection methods and etiologic
determinants. Participants completed both a general risk factor and a 137-item
food frequency questionnaire at baseline. A total of 1,338 cases of prostate
cancer were identified among 29,361 men during an average of 4.2 years of
follow-up.RESULTS: Lycopene intake was not associated with prostate cancer
risk. Reduced risks were also not found for total tomato servings or for most
tomato-based foods. Statistically nonsignificant inverse associations were noted
for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval
(95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06
and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and
spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95%
CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among
men with a family history of prostate cancer, risks were decreased in relation to
increased consumption of lycopene (P(trend)=0.04) and specific tomato-based
foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)=0.15;
lasagna, P(trend)=0.02).CONCLUSIONS: This large study does not support the
hypothesis that greater lycopene/tomato product consumption protects from
prostate cancer. Evidence for protective associations in subjects with a family
history of prostate cancer requires further corroboration. (Cancer Epidemiol
Biomarkers Prev 2006;15(1):92-8).
Emerging Issues208
Lessick, M and A. Katz (2006-DEC). "A genetics perspective on prostate cancer."
Urologic nursing: official journal of the American Urology association allied. 26(6): 454460.
Prostate cancer is the most common malignancy and the second leading cause
of cancer-related deaths among American men. In a small percentage of men,
prostate cancer occurs as a result of inheriting a mutation in a major gene
predisposing to this disease. The genome-wide search for prostate cancer
susceptibility genes holds the promise of making genetic testing for prostate
cancer risk available in the future and for ultimately developing better tools for
disease prevention, diagnosis, and treatment. Nursing practice roles are
increasingly affected by the translation of rapidly expanding genetic knowledge
into the patient care arena. The current advances in the genetic basis of prostate
cancer, including screening and management aspects and risk assessment
considerations for urologic nursing practice, are addressed.
Marcella S, Delnevo CD, Coughlin SS. (2007). "A national survey of medical students'
beliefs and knowledge in screening for prostate cancer." Journal of General internal
medicein 22(1): 80-85.
BACKGROUND: Today's medical students are being educated at a time when
there are no evidence-based guidelines for prostate cancer screening.
OBJECTIVE: To examine medical students' knowledge and beliefs concerning
prostate cancer screening and specific determinants for their beliefs. DESIGN,
SETTING, AND PARTICIPANTS: One thousand six hundred and forty four
students were sampled at 20 medical schools using a web-based, crosssectional survey. MAIN OUTCOME MEASURES: Basic knowledge and beliefs
about prostate cancer testing, epidemiology, and therapy were ascertained.
RESULTS: Four of 8 knowledge items were answered incorrectly by 50% or
more of students. Seven of 8 students believe that early diagnosis from
screening can improve survival from prostate cancer. Second- and third-year
students were more likely than fourth-year students to believe that the digital
rectal exam (DRE) and the prostate-specific antigen test were accurate, adjusted
odds ratio (AOR) 1.8; 95% confidence interval (CI), 1.2 to 2.7 and 1.7; 1.3 to 2.2
for second and third years, respectively, for the DRE. Black and Hispanic
students were no more likely than white students to agree that early screening
diagnosis improves survival, but blacks were more likely to agree with screening
black or Hispanic men (AOR 7.8; 95% CI, 5.3 to 11.4 and 3.2; 2.2 to 4.7,
respectively). More knowledgeable students were less likely to believe in the
benefit of early detection and the accuracy of the prostate-specific antigen (AOR
0.3; 95%CI, 0.2 to 0.5). CONCLUSIONS: Medical students generally are very
optimistic about the benefits of screening for prostate cancer. Increased
knowledge about prostate cancer is associated with a more conservative view of
screening. Other predictors are independent of this knowledge.
Markushin Y, Gaikwad N, Zhang H, Kapke P, Rogan EG, Cavalieri EL, Trock BJ,
Pavlovich C, Jankowiak R. (2006). "Potential biomarker for early risk assessment of
prostate cancer." Prostate 66(14): 1565-1571.
Emerging Issues209
BACKGROUND: Catechol estrogen quinones (CEQ) derived from 4hydroxyestrone (4-OHE1) and 4-hydroxyestradiol (4-OHE2) react with DNA to
form depurinating--N7Gua and--N3Ade adducts. This damage leads to mutations
that can initiate breast and prostate cancer. To determine whether this damage
occurs in humans, urine samples from men with prostate cancer and benign
urological conditions, and healthy controls were analyzed. The objective was
determining whether any of the cancer patients had formed the depurinating 4OHE1(E2)-1-N3Ade adducts. METHODS: The adducts were extracted from
samples by using affinity columns equipped with a monoclonal antibody
developed for detecting 4-OHE1(E2)-1-N3Ade adducts. Eluted extracts were
separated by capillary electrophoresis with field-amplified sample stacking and/or
ultraperformance liquid chromatography. Absorption/luminescence
spectroscopies and mass spectrometry were used to identify the adducts.
RESULTS: 4-OHE1-1-N3Ade was detected at higher levels in samples from
subjects with prostate cancer (n = 7) and benign urological conditions (n = 4)
compared to healthy males (n = 5). CONCLUSION: This is the first
demonstration that CEQ-derived DNA adducts are present in urine samples from
subjects with prostate cancer. (c) 2006 Wiley-Liss, Inc.
McFall, SL. (2006). "US men discussing prostate-specific antigen tests with a
physician." Annals of family medicine 4(5): 433-436.
PURPOSE: Informed decision making is recommended for prostate cancer
screening. I wanted to examine demographic and screening-related factors
associated with men's discussion of the advantages and disadvantages of
prostate-specific antigen (PSA) tests with their physicians. METHODS: I used
data from 2,184 men aged 50 years and older who reported a screening
prostate-specific antigen (PSA) test in the 2000 National Health Interview Survey
cancer control supplement. The dependent variable was discussion of the
advantages and disadvantages of the test before it was conducted. RESULTS:
Sixty-three percent of tested men reported a discussion in relation to their most
recent PSA test. Discussion was more common for African American men and
those with a usual source of care, and when the physician initiated the testing.
CONCLUSIONS: Characteristics of the patient-physician relationship were more
central to the discussion of risks and benefits than were patient attributes. Future
research should examine what role practice setting and the physician-patient
relationship play in a discussion of PSA testing and how to facilitate active
involvement of patients in decision making.
Morgan VA, Kyriazi S, Ashley SE, Desouza NM. (2007). "Evaluation of the potential of
diffusion-weighted imaging in prostate cancer detection." Acta Radiology 48(6): 695703.
Background: Conventional T2-weighted (T2W) imaging alone has a poor
sensitivity for prostate cancer detection. Purpose: To evaluate combined T2W
and diffusion-weighted magnetic resonance imaging (DW-MRI) versus T2W MRI
alone for identifying tumor in patients with prostate cancer. Material and
Methods: Fifty-four consecutive patients with prostate cancer (46 stage 1 and 2,
Emerging Issues210
8 stage 3) and sextant biopsies within the previous 3 months were studied.
Endorectal MR images were analyzed by two radiologists (1 experienced, 1
trainee) blinded to patient information and histopathology. T2W images were
scored first, followed by combined T2W and isotropic apparent diffusion
coefficient (ADC) maps calculated from DW-MRI (b = 0, 300, 500, and 800
s/mm(2)). Gland apex, middle, and base for each side were scored negative,
indeterminate, or positive for tumor. Imaging data for each sextant were
compared with histology. Sensitivity, specificity, and interobserver agreement
were calculated. Results: Sensitivity and specificity for tumor identification
significantly improved from 50% and 79.6% (T2W alone, experienced observer)
to 73.2% and 80.8% (P<0.001), respectively. For the trainee observer, there was
no improvement (44.3% and 72% T2W alone vs. 45.1% and 69.2% T2W plus
ADC maps). Interobserver agreement was moderate for T2W imaging alone
(kappa 0.51) and fair for T2W plus ADC maps (kappa 0.33). Conclusion: In an
experienced observer, DW-MRI together with T2W imaging can significantly
improve tumor identification in prostate cancer.
Moul JW, Sun L, Hotaling JM, Fitzsimons NJ, Polascik TJ, Robertson CN, Dahm P,
Anscher MS, Mouraviev V, Pappas PA, Albala DM. (2007). "Age adjusted prostate
specific antigen and prostate specific antigen velocity cut points in prostate cancer
screening." Journal of Urology 177(2): 499-503.
PURPOSE: We identified age adjusted prostate specific antigen and prostate
specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND
METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate
Center database. Of this group 11,861 men with 2 or more prostate specific
antigen values within 2 years were analyzed for age adjusted prostate specific
antigen and prostate specific antigen velocity performance in cancer risk
assessment using a receiver operating characteristic curve. RESULTS: In the
11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722
(17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or
older. In prostate cancer groups median prostate specific antigen and prostate
specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1
ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the
sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5
ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per
year, higher than those in men 70 years old or older at prostate specific antigen
4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing
the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific
antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old
improved the cancer detection rate but decreased the positive predictive value.
CONCLUSIONS: Current biopsy guidelines (prostate specific antigen 4.0 ng/ml
or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year)
underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen
and prostate specific antigen velocity cut points should be age adjusted. In men
50 to 59 years old prostate specific antigen and prostate specific antigen velocity
cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively.
Emerging Issues211
Factors of age, sensitivity, specificity, positive predictive value and cancer
prevalence are critical for obtaining the desired balance between cancer
detection and negative biopsy.
Oliffe, J and S Thorne (2007- Feb). "Men, masculinities, and prostate cancer: Australian
and Canadian patient perspectives of communication with male physicians." Qualitative
Health Research 17(2): 149-161.
Patient-physician communication is vital in cancer care, and aspects of the
patients' experiences provide insight into what constitutes effective cancer
communication. Complexities inherent in prostate cancer regarding screening,
treatment(s) efficacy, and side effects commonly form the basis of patientphysician discussions. However, the specificities of patient-physician
communications, particularly in the male dyad, and the connections to
masculinity are poorly understood. The authors used secondary analysis of data
from two interview studies of 19 Canadian and 33 Australian prostate cancer
survivors who were treated by male general practitioners and prostate cancer
specialists. Participants acknowledged that physician expertise and compassion
underpinned the development of trust, and both reassurance and humor were
effective communication strategies. Participants were often self-directed in
researching prostate cancer, consistently using biomedical language and
numerical markers when discussing their disease. Analysis of findings enabled
interpretations regarding what might be considered prostate cancer
communication competencies in the male patient-physician dyad.
Pickles T, Ruether JD, Weir L, Carlson L, Jakulj F (2007). "Psychosocial barriers to
active surveillance for the management of early prostate cancer and a strategy for
increased acceptance." BJU international ahead of print.
OBJECTIVES To review the psychosocial needs of men undergoing active
surveillance (AS, the monitoring of early prostate cancer, with curative
intervention only if the disease significantly progresses) for prostate cancer, and
barriers to its uptake. METHODS The introduction of screening for prostatespecific antigen (PSA) has led to more men diagnosed with early and nonlifethreatening forms of prostate cancer; about half of men diagnosed as a result of
PSA testing have cancers that would never cause symptoms if left untreated and
yet up to 90% of such men receive curative therapy, then living with the toxicity of
treatment but with no benefit. Thus AS is increasingly being promoted, but if such
a strategy is to succeed, the psychosocial barriers that discourage men from
adopting AS must be addressed. We reviewed and assessed reports on this
topic, published in English since 1994. RESULTS There is relatively little
research on AS, as most published reports refer to watchful waiting (which is a
palliative management approach). Men with prostate cancer generally have lower
levels of psychological disturbance than for other cancers, but the psychosocial
issues identified include anxiety in response to no intervention, uncertainty
related to loss of control, and lack of patient education and support, particularly
around the time of initial treatment planning. Approaches that were identified to
improve uptake of AS include increased education and improved communication,
Emerging Issues212
interventions to reduce anxiety and uncertainty, and the empowerment of
patients by the development of a sense of control and meaning. Physicians
attitudes are influential and the education of physicians about AS as an
appropriate option is to be encouraged. Peer-support groups were also identified
as being of particular value. CONCLUSIONS There are several strategies that
should be developed if AS is to become more widely adopted. Increased
education and good communication can alleviate anxiety and uncertainty, as can
interventions for cognitive re-framing. Inviting patients to become active
participants in their management might enhance the patients' sense of control,
and the involvement of peer-support groups might be beneficial.
Platz, EA, MF Leitzmann, K Visvanathan, EB Rimm, MJ Stampfer, WC Willett and E
Giovannucci (2006-DEC). "Statin drugs and risk of advanced prostate cancer." J Natl
Cancer Inst.
BACKGROUND: Statins are commonly used cholesterol-lowering drugs that
have proapoptotic and antimetastatic activities that could affect cancer risk or
progression. Results from previous epidemiologic studies of the association
between statin use and cancer have been inconsistent. We investigated the
association of statin use with total and advanced prostate cancer, the latter being
the most important endpoint to prevent. METHODS: We analyzed data from an
ongoing prospective cohort study of 34,989 US male health professionals who
were cancer free in 1990 and were followed to 2002. Participants reported their
use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer
diagnosis was confirmed by medical record review. Multivariable-adjusted
relative risks (RRs) were estimated from Cox proportional hazards regression
models. Statistical tests were two-sided. RESULTS: During 376,939 personyears of follow-up, we ascertained 2579 prostate cancer cases, 316 of which
were advanced (regionally invasive, metastatic, or fatal). The age-standardized
incidence rates of advanced prostate cancer were 38 and 89 per 100,000
person-years in current statin users and in past or never users, respectively. The
multivariable-adjusted relative risk of advanced disease was 0.51 (95%
confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was
0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use.
The associations remained after adjusting for prostate-specific antigen screening
history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal
disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower
with longer statin use (P(trend) = .003); compared with never use, the relative
risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or
more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association
between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to
1.09). CONCLUSIONS: In this cohort of male health professionals, use of statin
drugs was not associated with risk of prostate cancer overall but was associated
with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.
Reinberg, Steven. (2007). "Many Men Getting Unnecessary Prostate Cancer Blood
Tests." from
Emerging Issues213
http://news.yahoo.com/s/hsn/20070709/hl_hsn/manymengettingunnecessaryprostateca
ncerbloodtests.
Ross LE, Richardson LC, Berkowitz Z. (2006). "The effect of physician-patient
discussions on the likelihood of prostate-specific antigen testing." journal of the national
medical association 98(11): 1823-1829.
Many medical and professional organizations agree that men should discuss the
advantages and disadvantages of testing for prostate-specific antigen (PSA) with
their physicians before undergoing testing. In the 2000 National Health Interview
Survey, men who had undergone a PSA test in the past were asked about their
use of this test and discussions they had with physicians regarding its
advantages and disadvantages. Among a group of 2,188 black and white men
aged 40-79 years with no history of prostate cancer and a history of testing for
PSA, we examined whether physician-patient discussions mediated the
relationship between race and PSA testing. We specified that the test had to be
their most recent one and part of a routine physical examination or screening
test. We compared those tested within the past two years with those tested >2
years. Almost two-thirds of the men previously had discussions with their
physicians about the advantages and disadvantages of the PSA test. Older men,
college graduates, those living in the midwest and those with health insurance
were more likely to have been tested recently. Discussion with a physician was
found to mediate the relationship between race and PSA testing during the past
two years. Black men were initially found to be more likely than white men to
have been screened recently [odds ratio (OR)=1.45; 95% confidence interval (CI)
1.01-2.07], but in the full model race was no longer significant (OR=1.41; 95% Cl
0.98-2.03). Discussions about PSA testing were associated with more recent
PSA screening (OR=1.38, 95% CI 1.05-1.82). These findings suggest that: 1) the
relationships among race, physician discussions and PSA testing may need to be
examined in more complex ways, and 2) the physician has an important role in
men's decision to consider PSA testing.
Schnur JB, DiLorenzo TA, Montgomery GH, Erblich J, Winkel G, Hall SJ, Bovbjerg DH.
(2006). "Perceived risk and worry about prostate cancer: a proposed conceptual
model." behavioral medicine 32(3): 89-96.
Prostate cancer is one of the most common forms of cancer among American
men, and worry about the disease has psychological, behavioral, and biological
consequences. To better understand prostate cancer-specific worry, the authors
tested a model of the interrelationships among family history of prostate cancer;
perceived risk of and worry about prostate cancer; and perceived risk of and
worry about other diseases. Men who attended prostate cancer-screening
appointments at a general urology practice (n=209) were given a brief
anonymous self-report measure. Structural equation modeling (LISREL) results
indicated: (1) perceived risk of prostate cancer mediated the relationship
between family history of prostate cancer and prostate cancer worry; (2)
perceived risk of other diseases increased perceived risk of prostate cancer; and
(3) prostate cancer worry and increased other disease worry.
Emerging Issues214
Stephenson AJ, Kuritzky L, Campbell SC. (2007). "Screening for urologic malignancies
in primary care: pros, cons, and recommendations." cleveland clinic journal of medicine
74 (supplement 3:s6-7).
Interest in screening for urologic cancers has grown in recent years. This article
considers the pros and cons of screening for four epidemiologically compelling
urologic cancers: prostate, bladder, kidney, and testicular. Unfortunately, many of
the urologic cancers do not meet the criteria for a successful cancer screening
program-namely, high prevalence, availability of a sensitive and specific
screening test, ability to detect clinically important cancers at an early stage, and
cost-effectiveness. While age-based screening for prostate cancer should be
offered to the general population after discussion of its benefits and risks, for the
other three urologic malignancies the current consensus points more toward
selective screening based on specific patient risk factors.
Thompson IM, Ankerst DP, Chi C, Goodman PJ, Tangen CM, Lucia MS, Feng Z,
Parnes HL, Coltman CA. (2006). "Assessing prostate cancer risk: results from the
Prostate Cancer Prevention Trial." Journal of the National Cancer Institute 19(98): 529534.
BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method
used to diagnose prostate cancer in the United States. Methods to integrate
other risk factors associated with prostate cancer into individualized risk
prediction are needed. We used prostate biopsy data from men who participated
in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of
prostate cancer. METHODS: We included 5519 men from the placebo group of
the PCPT who underwent prostate biopsy, had at least one PSA measurement
and a digital rectal examination (DRE) performed during the year before the
biopsy, and had at least two PSA measurements performed during the 3 years
before the prostate biopsy. Logistic regression was used to model the risk of
prostate cancer and high-grade disease associated with age at biopsy, race,
family history of prostate cancer, PSA level, PSA velocity, DRE result, and
previous prostate biopsy. Risk equations were created from the estimated logistic
regression models. All statistical tests were two-sided. RESULTS: A total of 1211
(21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables
that predicted prostate cancer included higher PSA level, positive family history
of prostate cancer, and abnormal DRE result, whereas a previous negative
prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA
velocity contributed independent prognostic information. Higher PSA level,
abnormal DRE result, older age at biopsy, and African American race were
predictive for high-grade disease (Gleason score > or =7) whereas a previous
negative prostate biopsy reduced this risk. CONCLUSIONS: This predictive
model allows an individualized assessment of prostate cancer risk and risk of
high-grade disease for men who undergo a prostate biopsy.
Wicht A, Hamza A, Loertzer H, Dietl M, Heynemann H, Fornara P. (2006). "[Diagnostics
and treatment of prostate cancer after kidney transplantation]." Urologe A. 45(1): 32-37.
Emerging Issues215
The number of patients with prostate cancer and end-stage renal disease or
prostate cancer following kidney transplantation has continuously increased in
industrialized countries. According to the data generated by Penn et al. a higher
incidence of prostate cancer following kidney transplantation can be seen but is
probably due to a more intense screening of the recipients. It is rather a common
opinion that no elevated risk of prostate cancer following kidney transplantation
exists.In patients with strictly localized prostate cancer curative treatment should
be the aim also after kidney transplantation. Kidney transplantation does not
interfere with surgical access to the prostate gland (retropubic or perineal).
Nonlocal tumors of the prostate should also be treated following the general
recommendations regarding prostate cancer. Looking at the current literature, a
reduction or change of immunosuppression seems reasonable. It is necessary to
establish a nationwide (or even European) cancer register, especially for patients
before and after transplantation.
Emerging Issues216
Colorectal Screening
CDC. (2005). "Colorectal screening and prevention information." from
http://www.cdc.gov/cancer/colorectal/statistics/screening_rates.htm.
CDC. (2007). "COLORECTAL CANCER INITIATIVES." from
http://www.cdc.gov/cancer/colorectal/pdf/0607_colorectal_fs.pdf.
Colorectal Cancer Coalition. (2007). "State Updates for New Hampshire ", from
http://www.fightcolorectalcancer.org/advocacy/2007/04/state_updates_from_california.p
hp.
Driver, Jane A., J. Michael Gaziano, Rebecca P. Gelber, I. Min Lee, Julie E. Buring and
Tobias Kurth (2007). "Development of a risk score for colorectal cancer in men."
American Journal of Medicine 120(3): 257-263.
BACKGROUND: Colorectal cancer is a common and preventable disease for
which screening rates remain unacceptably low.METHODS: We developed a risk
scoring system for the development of colorectal cancer among participants in
the Physician's Health Study, a prospective cohort of 21,581 US male physicians
who were all free of cancer. Predictors of colorectal cancer were self-reported
and identified from the baseline questionnaire. Logistic regression was used to
determine the independent predictors of incident colorectal cancer over the
follow-up period. Risk scores were created from the sum of the odds ratios of the
final predictors and used to divide the cohort into categories of increasing relative
risk.RESULTS: During 20 years of follow-up, 381 cases of colon cancer and 104
cases of rectal cancer developed in the cohort. Age, alcohol use, smoking status,
and body mass index were independent significant predictors of colorectal
cancer. The point scores were used to define 10 risk groups. Those in the
highest risk group (9-10 points) had an odds ratio of 15.29 (6.19-37.81) for
colorectal cancer compared with those with the lowest risk. We further stratified
scores into 3 risk classes. Compared with those at the lowest relative risk, the
odds ratio for colorectal cancer was 3.07 (2.46-3.83) in the intermediate risk
group and 5.75 (4.44-7.44) in the highest risk group.CONCLUSIONS: We
developed a simple scoring system for colorectal cancer that identifies men at
increased relative risk on the basis of age and modifiable factors. This tool
should be validated in other populations. (c) 2007 Elsevier Inc. All rights
reserved.
Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, Lamerz R,
Peltomaki P, Sturgeon C, Topolcan O. (2007). "Tumour markers in colorectal cancer:
European Group on Tumour Markers (EGTM) guidelines for clinical us." European
journal of cancer 43(9): 1348-1360.
The aim of this article is to present updated guidelines for the use of serum,
tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and
Emerging Issues217
sensitivity preclude the use of all existing serum markers for the early detection
of CRC. For patients with stage II or stage III CRC who may be candidates for
either liver resection or systemic treatment should recurrence develop, CEA
should be measured every 2-3 months for at least 3 years after diagnosis.
Insufficient evidence exists to recommend routine use of tissue factors such as
thymidylate synthase, microsatellite instability (MSI), p53, K-ras and deleted in
colon cancer (DCC) for either determining prognosis or predicting response to
therapy in patients with CRC. Microsatellite instability, however, may be used as
a pre-screen for patients with suspected hereditary non-polyposis colorectal
cancer. Faecal occult blood testing but not faecal DNA markers may be used to
screen asymptomatic subjects 50 years or older for early CRC.
Friedman, M and ML. Borum (2007). "Colon cancer screening consultations may
identify racial disparity in hypertension diagnosis and management." J Natl Med Assoc.
99(5): 525-526.
There are significant health disparities between African Americans and whites in
the United States. While colon cancer screening aids in decreasing the morbidity
and mortality from colon cancer in African Americans, other health risks may also
be identified during gastroenterology consultations. This study evaluated whether
there is a disparity in the prevalence of hypertension and hypertension
management in African Americans compared to whites who are referred for colon
cancer screening consultations. The medical records of 258 patients (90 African
Americans and 168 whites) were reviewed. Seventy-two of 90 (80%) AfricanAmerican patients and 42 of 168 (25%) white patients had hypertension. There
was a statistically significant difference (p < 0.005) in the rate of hypertension in
African Americans compared to whites. Medications were prescribed by their
referring physicians for 42 (58%) of the hypertensive African Americans, with 36
noted to have inadequately controlled blood pressure. Thirty (42%) of the
hypertensive African-American patients were never prescribed blood pressure
medications. Medications were prescribed by their referring physician for 36
(86%) of the hypertensive white patients, with six noted to have inadequately
controlled blood pressure. Six (14%) of the hypertensive white patients were
never prescribed blood pressure medications. There was a statistically significant
difference in the rate of blood pressure control (p = 0.007) between AfricanAmerican and white patients who were referred for colon cancer screening.
Increased efforts are necessary to identify critical health concerns of all patients
and to decrease health disparities between African Americans and whites in the
United States.
Greco, K. (2007). "Caring for patients at risk for hereditary colorectal cancer." Oncology
21((2 Suppl Nurse Ed):): 29-38; discussion 39.
About 6% of colorectal cancers are caused by genetic mutations associated with
hereditary colorectal cancer syndromes. The most common hereditary cancer
syndromes nurses are likely to encounter include hereditary nonpolyposis colon
cancer or Lynch syndrome, familial adenomatous polyposis, attenuated familial
adenomatous polyposis, and MYH polyposis. Current colorectal cancer
Emerging Issues218
recommendations for risk management, screening, and surveillance are complex
and based on level of colorectal cancer risk and whether an individual carries a
genetic mutation associated with a hereditary colorectal cancer syndrome.
Caring for patients with hereditary colorectal cancer syndromes requires nurses
to understand how to identify individuals and families at risk for hereditary
colorectal cancer, refer to appropriate resources, and provide accurate
information regarding screening, surveillance, and management. Nurses play a
critical role in assessing colorectal cancer risk, obtaining an accurate family
history of cancer, and providing information concerning appropriate cancer
screening and surveillance.
Greiner, K. Allen, Wendi Born, Nicole Nollen and Jasjit S. Ahluwalia (2005). "Knowledge
and Perceptions of Colorectal Cancer Screening Among Urban African Americans."
Journal of General Internal Medicine 20(11): 977-983.
Objective: To explore colorectal cancer (CRC) screening knowledge, attitudes,
barriers, and preferences among urban African Americans as a prelude to the
development of culturally appropriate interventions to improve screening for this
group. Design: Qualitative focus group study with assessment of CRC screening
preferences. Setting: Community health center serving low-income African
Americans. Participants: Fifty-five self-identified African Americans over 40 years
of age. Measurements and Main Results: Transcripts were analyzed using an
iterative coding process with consensus and triangulation on final thematic
findings. Six major themes were identified: (1) Hope-a positive attitude toward
screening, (2) Mistrust-distrust that the system or providers put patients first, (3)
Fear-fear of cancer, the system, and of CRC screening procedures, (4) Fatalismthe belief that screening and treatment may be futile and surgery causes spread
of cancer, (5) Accuracy-a preference for the most thorough and accurate test for
CRC, and (6) Knowledge-lack of CRC knowledge and a desire for more
information. The Fear and Knowledge themes were most frequently noted in
transcript theme counts. The Hope and Accuracy themes were crucial
moderators of the influence of all barriers. The largest number of participants
preferred either colonoscopy (33%) or home fecal occult blood testing (26%).
Conclusions: Low-income African Americans are optimistic and hopeful about
early CRC detection and believe that thorough and accurate CRC screening is
valuable. Lack of CRC knowledge and fear are major barriers to screening for
this population along with mistrust, and fatalism.
Gross, Cary P., Martin S. Andersen, Harlan M. Krumholz, Gail J. McAvay, Deborah
Proctor and Mary E. Tinetti (2006). "Relation between Medicare screening
reimbursement and stage at diagnosis for older patients with colon cancer." JAMA
(Journal of the American Medical Association) 296(23): 2815-2822.
Context Medicare's reimbursement policy was changed in 1998 to provide
coverage for screening colonoscopies for patients with increased colon cancer
risk, and expanded further in 2001 to cover screening colonoscopies for all
individuals.Objective To determine whether the Medicare reimbursement policy
changes were associated with an increase in either colonoscopy use or early
Emerging Issues219
stage colon cancer diagnosis.Design, Setting, and Participants Patients in the
Surveillance, Epidemiology, and End Results Medicare linked database who
were 67 years of age and older and had a primary diagnosis of colon cancer
during 1992-2002, as well as a group of Medicare beneficiaries who resided in
Surveillance, Epidemiology, and End Results areas but who were not diagnosed
with cancer.Main Outcome Measures Trends in colonoscopy and sigmoidoscopy
use among Medicare beneficiaries without cancer were assessed using
multivariate Poisson regression. Among the patients with cancer, stage was
classified as early ( stage I) vs all other ( stages II-IV). Time was categorized as
period 1 ( no screening coverage, 19921997), period 2 ( limited coverage,
January 1998-June 2001), and period 3 ( universal coverage, July 2001December 2002). A multivariate logistic regression (outcome = early stage) was
used to assess temporal trends in stage at diagnosis; an interaction term
between tumor site and time was included.Results Colonoscopy use increased
from an average rate of 285/ 100 000 per quarter in period 1 to 889 and
1919/100 000 per quarter in periods 2 ( P <. 001) and 3 ( P vs 2 <. 001),
respectively. During the study period, 44 924 eligible patients were diagnosed
with colorectal cancer. The proportion of patients diagnosed at an early stage
increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in period 3 ( P
<. 001 for each pair-wise comparison). The changes in Medicare coverage were
strongly associated with early stage at diagnosis for patients with proximal colon
lesions ( adjusted relative risk period 2 vs 1, 1.19; 95% confidence interval, 1.131.26; adjusted relative risk period 3 vs 2, 1.10; 95% confidence interval, 1.021.17) but weakly associated, if at all, for patients with distal colon lesions (
adjusted relative risk period 2 vs 1, 1.07; 95% confidence interval, 1.01-1.13;
adjusted relative risk period 3 vs 2, 0.97; 95% confidence interval, 0.901.05).Conclusions Expansion of Medicare reimbursement to cover colon cancer
screening was associated with an increased use of colonoscopy for Medicare
beneficiaries, and for those who were diagnosed with colon cancer, an increased
probability of being diagnosed at an early stage. The selective effect of the
coverage change on proximal colon lesions suggests that increased use of
whole-colon screening modalities such as colonoscopy may have played a
pivotal role.
Kohut K, Manno M, Gallinger S, Esplen MJ. (2007). "Should healthcare providers have
a duty to warn family members of individuals with an HNPCC-causing mutation? A
survey of patients from the Ontario Familial Colon Cancer Registry." Journal of Medical
genetics 44(6): 404-7.
BACKGROUND: As genetic testing becomes more common and increasingly
intertwined with medical care, the issues of genetic privacy and doctor-patient
confidentiality are being examined. Hereditary non-polyposis colorectal cancer
(HNPCC) is a genetic predisposition to colorectal and certain other cancers.
Effective screening that can prevent colorectal cancer is an important incentive
for genetic testing. METHODS: A survey regarding the duty to warn family
members of the risks associated with an HNPCC-causing mutation was mailed to
227 participants in the Ontario Familial Colon Cancer Registry (OFCCR). To our
Emerging Issues220
knowledge, the opinions of patients on this subject have not been reported
previously in the literature. Responses were analysed quantitatively using the
SAS system and qualitatively by the review of written comments. RESULTS:
Completed surveys were returned by 105 participants, with a response rate of
46.3%. The majority felt a personal responsibility to warn relatives, but there was
no significant agreement that doctors or genetic counsellors should have a duty
to warn relatives without a patient's permission. CONCLUSIONS: Patients
undergoing genetic testing for HNPCC generally understand that relatives could
benefit from being informed of genetic risk, but may not be willing or able to
inform each family member. Healthcare professionals should engage patients in
a discussion of familial implications before genetic testing. An agreement should
be formulated regarding which of the relatives should be informed. Patients
should be encouraged to personally disseminate the information, given the
unrealistic burden on practitioners to perform this task and patients' preference
for control over the information.
Latimes.org. (2007). "New Colon Test Promising." from
http://www.latimes.com/news/science/la-na-colon6jul06,1,2357058.story?track=rss.
Menon U, Belue R, Sugg Skinner C, Rothwell BE, Champion V. (2007). "Perceptions of
colon cancer screening by stage of screening test adoption." Cancer Nursing 30(3):
178-85.
Colorectal cancer remains the second leading cause of cancer death in the
United States. To fully realize the benefits of early detection of colorectal cancer,
screening rates must improve. This study assessed differences in beliefs (from
the Health Belief Model) by stage of screening behavior adoption (based on the
Transtheoretical Model of Change) as a foundation for intervention development.
More people were in the precontemplation stage (not thinking about having the
screening test) for fecal occult blood test and sigmoidoscopy versus
contemplation (thinking about having the test) or action (adherent with
screening). Those in precontemplation stage for fecal occult blood test had lower
perceived risk than those in contemplation, lower perceived benefits than those
in action, and higher barriers than both those in contemplation and those in
action. For sigmoidoscopy stage of readiness, again, precontemplators had lower
perceived risk and self-efficacy than contemplators and higher barriers than both
contemplators and actors. Given the popularity of the transtheoretical model and
the success of stage-based interventions to increase other cancer screening,
especially mammography, we should begin to translate such effective
interventions to colorectal cancer screening. As such, this study is one of very
few to quantify beliefs across stages of colorectal cancer and identify significant
differences across stages, laying the foundation for the development and testing
of stage-based interventions.
Pasetto, LM and S. Monfardini (2007). "Colorectal cancer screening in elderly patients:
When should be more useful?" Cancer treatment and prevention ahead of print.
Emerging Issues221
Current guidelines endorse colon cancer screening every 5-10 years in persons
over 50 years of age. However, there is no consensus regarding what age is
appropriate to stop screening. Prior history of neoplasia seems to be a strong risk
factor for colorectal neoplasia development in elderly people and should be
considered when deciding the need for continuing screening/surveillance,
however, clinical judgment of comorbidities is still required to individualize
screening practice. Screening colonoscopy in very elderly persons (aged 80
years), i.e. should be performed only after careful consideration of potential
benefits, risks and patient preferences. The aims of this paper are to: (1)
determine the best type of colorectal cancer screening (faecal occult blood
testing, flexible sigmoidoscopy, double-contrast barium enema and colonoscopy)
and its association with age and health status among elderly veterans and (2)
describe the outcomes of colorectal cancer screening among older veterans who
have widely differing life expectancies (based on age and health status).
Shenson, Douglass, Julie Bolen, Mary Adams, Laura Seef and Donald Blackman
(2005). "Are Older Adults Up-To-Date with cancer screening and vaccinations."
Preventing Chronic Disease 2 No:3.
Walsh, Judith (2005). "Colorectal Cancer Screening. The Time Is Now!" Journal of
General Internal Medicine 20(11): 1068-1070.
Young WF, McGloin J, Zittleman L, West DR, Westfall JM. (2007). "Predictors of
colorectal screening in rural colorado: testing to prevent colon cancer in the high plains
research network." Journal of Rural health 23(3): 238-45.
Context:Colorectal cancer is the second leading cause of cancer death in the
United States, yet screening rates are well below target levels. Rural
communities may face common and unique barriers to health care, particularly
preventive health care.Purpose:To establish baseline attitudinal, knowledge,
belief, and behavior measures on colorectal cancer screening and to identify
barriers to or predictors of colorectal cancer screening.Methods:As part of a
controlled trial using a quasi-experimental, pretest, post-test design, we
conducted a baseline telephone survey of 1,050 rural eastern Colorado residents
aged 50 years and older. Smaller counties were over-sampled to ensure a
minimum of 30 completed interviews per county.Findings:Seventy-seven percent
reported they ever had a colorectal cancer screening test and 59% were up-todate on at least 1 test. The most important independent predictors of being up-todate were having visited a doctor or other health care practitioner for a checkup
in the past year, having personal or family history of colon polyps or cancer, and
having asked for a colorectal cancer screening test. Financial concerns were
reported reasons for not obtaining fecal occult blood testing by 18% and
colonoscopy by 21%.Conclusions:This study suggests that health care providers
should be vigilant in counseling their patients 50 and older to have a colorectal
cancer test. Community programs designed to promote colon cancer screening
should encourage residents to have regular contact with their primary care
Emerging Issues222
physician and ask their doctor for a screening test. Additionally, programs should
provide financial assistance for testing for low-income and uninsured patients.
Emerging Issues223
SECTION C: TREATMENT AND SURVIVORSHIP
Emerging Issues224
Radiation and Chemotherapy
Ahles, T. A., A. J. Saykin, C. T. Furstenberg, B. Cole, L. A. Mott, K. Skalla, M. B.
Whedon, S. Bivens, T. Mitchell, E. R. Greenberg and P. M. Silberfarb (2002).
"Neuropsychologic impact of standard-dose systemic chemotherapy in long-term
survivors of breast cancer and lymphoma." J Clin Oncol 20(2): 485-93.
PURPOSE: The primary purpose of this study was to compare the
neuropsychologic functioning of long-term survivors of breast cancer and
lymphoma who had been treated with standard-dose systemic chemotherapy or
local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years
postdiagnosis, not presently receiving cancer treatment, and disease-free) of
breast cancer or lymphoma who had been treated with systemic chemotherapy
(breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years;
lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of
neuropsychologic and psychologic tests (Center for Epidemiological StudyDepression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom
Inventory). RESULTS: Multivariate analysis of variance, controlling for age and
education, revealed that survivors who had been treated with systemic
chemotherapy scored significantly lower on the battery of neuropsychologic tests
compared with those treated with local therapy only (P <.04), particularly in the
domains of verbal memory (P <.01) and psychomotor functioning (P <.03).
Survivors treated with systemic chemotherapy were also more likely to score in
the lower quartile on the Neuropsychological Performance Index (39% v 14%, P
<.01) and to self-report greater problems with working memory on the Squire
Memory Self-Rating Questionnaire (P <.02). CONCLUSION: Data from this study
support the hypothesis that systemic chemotherapy can have a negative impact
on cognitive functioning as measured by standardized neuropsychologic tests
and self-report of memory changes. However, analysis of the Neuropsychological
Performance Index suggests that only a subgroup of survivors may experience
long-term cognitive deficits associated with systemic chemotherapy.
Bangalore, M., S. Matthews and M. Suntharalingam (2007). "Recent advances in
radiation therapy for head and neck cancer." ORL J Otorhinolaryngol Relat Spec 69(1):
1-12.
The treatment of locally advanced or recurrent head and neck cancers has
improved from single modality interventions of surgery and radiation therapy
alone to include combined modality therapy with surgery, chemotherapy and
radiation. Combined therapy has led to improved local control and disease-free
survival. New developments in radiation oncology such as altered fractionation,
three-dimensional conformal radiotherapy, intensity-modulated radiotherapy,
stereotactic radiosurgery, fractionated stereotactic radiotherapy, charged-particle
radiotherapy, neutron-beam radiotherapy, and brachytherapy have helped to
improve this outlook even further. These recent advances allow for a higher dose
Emerging Issues225
to be delivered to the tumor while minimizing the dose delivered to the
surrounding normal tissue. This article provides an update of the new
developments in radiotherapy in the management of head and neck cancers.
Calabro, F. and C. N. Sternberg (2007). "Current indications for chemotherapy in
prostate cancer patients." Eur Urol 51(1): 17-26.
Recently, data from two randomized studies, TAX327 and SWOG 9916, which
compared docetaxel-based chemotherapy to mitoxantrone-based therapy, have
demonstrated that treatment with docetaxel can prolong life in a statistically
significant way in patients with hormone refractory prostate cancer (HRPC). In
the TAX237 trial the median overall survival rates for patients treated with
docetaxel every 3 wk was 18.9 mo, compared with 16.4 mo for the patients in the
control arm (p=0.009). Patients treated with the combination of docetaxel and
estramustine in the SWOG trial had a significant improvement in median survival
(18 mo vs 16 mo, p=0.01), longer progression-free survival (6 mo compared with
3 mo, p<0.0001), and a 20% reduction in the risk of death. The optimal timing of
docetaxel-based chemotherapy is still unknown because there are no
prospective clinical trials indicating whether earlier treatment is more effective
than delayed treatment. There are now increasing options also for second-line
therapies in the palliative treatment of HRPC, and ongoing studies on new drugs
such as satraplatin and ixabepilone will define the role of these agents in this
setting. Preliminary neoadjuvant and adjuvant chemotherapy studies in high-risk
prostate cancer patients have demonstrated that these approaches are feasible
and do not add morbidity to surgery or radiotherapy, but their impact on survival
still needs to be proven in randomized studies.
Conti, F., D. Sergi, P. Foggi, M. I. Abbate and M. Lopez (2007). "[New combination
chemotherapy regimens in the primary treatment of operable breast cancer]." Clin Ter
158(1): 55-75.
Primary (neoadjuvant) systemic chemotherapy is the standard treatment for
locally advanced breast cancer and a standard option for primary operable
disease. Although survival results are similar, primary chemotherapy has the
following advantages in comparison to adjuvant chemotherapy: it represents a
chemosensitivity test in vivo and can be of value in determining the prognosis of
the patient since pathologic complete responses are related to improved survival.
Among a variety of primary chemotherapy regimens currently available, the most
effective seem to be those containing both anthracyclines and taxanes,
expecially when these agents are administered sequentially. There are also
several ongoing studies evaluating primary hormonal therapy and the
combination of cytotoxic chemotherapy and targeted agents. It is conceivable
that in the future primary chemotherapy of breast cancer will be increasingly
used. In fact, besides its clinical effectiveness, primary chemotherapy is
extremely important to evaluate new agents and to find useful prognostic and
predictive factors.
Emerging Issues226
Crivellari, G., S. Monfardini, S. Stragliotto, D. Marino and S. M. Aversa (2007).
"Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to
megadoses." Oncologist 12(1): 79-89.
The hypothesis that increasing cytotoxic dose intensity will improve cancer cure
rates is compelling. Although supporting evidence for this hypothesis has
accrued for several tumor types, including lymphomas, breast cancer, and
testicular cancers, it remains unproven. Small-cell lung cancer is extremely
chemo- and radiosensitive, with a response rate of 80% achieved routinely, but
few patients are cured by chemoradiotherapy. In this setting, increased cytotoxic
dose intensity might improve cure rates. The finding that response rates in smallcell lung cancer correlate with received cytotoxic dose intensity merely confirms
that "less is worse" and "more is better." Within conventional ranges, dose
intensity can be increased with the support of hematopoietic growth factors
and/or by shortening treatments intervals; however, dose intensity could be
increased by only 20%-30%, and a survival advantage has not been clearly
demonstrated. Given its high chemosensitivity, small-cell lung cancer was one of
the first malignancies deemed suitable for increasing dose intensity and even for
the use of a megadose with the support of autologous bone marrow
transplantation. Some interest is emerging again due to improvements in
supportive care, such as the availability of hematopoietic growth factors and
peripheral blood progenitor cells.
Dignam, James J., Blase N. Polite, Greg Yothers, Peter Raich, Linda Colangelo,
Michael J. O'Connell and Norman Wolmark (2006). "Body mass index and outcomes in
patients who receive adjuvant chemotherapy for colon cancer." Journal of the National
Cancer Institute (Cary) 98(22): 1647-1654.
Background: Although several studies have established a link between obesity
and colon cancer risk, little is known about the effect of obesity on outcomes after
diagnosis. We investigated the association of body mass index (BMI) with
outcomes after colon cancer in patients from cooperative group clinical trials.
Methods: The study cohort consisted of 4288 patients with Dukes B and C colon
cancer who were accrued from July 1989 to February 1994 to National Surgical
Adjuvant Breast and Bowel Project randomized trials. Risk of recurrence, second
primary cancer, and mortality (overall and by likely cause) were evaluated in
relation to BMI at diagnosis using statistical modeling. Median follow-up time was
11.2 years. All statistical tests were two-sided. Results: Very obese patients (BMI
>= 35 kg/m(2)) had greater risk of a colon cancer event (recurrence or secondary
primary tumor; hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.10 to
1.73) than normal weight patients (BMI = 18.5-24.9 kg/m(2)). Mortality was
greater for very obese (HR = 1.28, 95% CI = 1.04 to 1.57) and underweight (BMI
< 18.5 kg/m(2)) (HR = 1.49, 95% CI = 1.17 to 1.91) than for normal weight
patients. The increased risk of mortality for underweight patients was dominated
by non-colon cancer deaths (HR of such deaths compared with normal weight
patients = 2.23,95% CI = 1.50 to 3.31), whereas for the very obese, deaths likely
due to colon cancer were increased (HR = 1.36, 95% CI = 1.06 to 1.73).
Conclusions: Among colon cancer patients, a BMI greater than 35.0 kg/m(2) at
Emerging Issues227
diagnosis was associated with an increased risk for recurrence of and death from
colon cancer. Further studies are needed to determine pathways between
obesity and recurrence risk and whether weight reduction or related interventions
would improve prognosis.
Farquhar, C. M., J. Marjoribanks, A. Lethaby and R. Basser (2007). "High dose
chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis."
Cancer Treat Rev 33(4): 325-37.
BACKGROUND: High dose chemotherapy with autologous transplantation of
bone marrow or peripheral stem cells (autograft) has been considered promising
for treating poor prognosis breast cancer. We reviewed the relevant evidence.
METHODS: We included randomised controlled trials comparing high dose
chemotherapy and autograft with conventional chemotherapy for women with
early poor prognosis breast cancer. We searched medical databases (Cochrane
Library, MEDLINE, EMBASE), websites (co-operative cancer research groups,
American Society of Clinical Oncologists) and citations of articles found, to
September 2006. Where appropriate, data were pooled to obtain a relative risk,
using a fixed effects model. Clinical, methodological and statistical heterogeneity
were examined with sensitivity analyses. FINDINGS: Thirteen trials with 5064
women were included. There was a significant benefit in event-free survival for
the high dose group at three years (RR 1.19 (95% CI 1.06, 1.19)) and four years
(RR 1.24 (95% CI 1.03, 1.50)) and at five years this benefit approached statistical
significance (RR 1.06 (95% CI 1.00, 1.13)). Overall survival rates were not
significantly different at any stage of follow up. There were significantly more
treatment-related deaths on the high dose arm (RR 8.58 (95% CI 4.13, 17.80)).
Morbidity was higher in the high dose group but there was no significant
difference in the incidence of second cancers. The high dose group reported
significantly worse quality of life immediately after treatment, but there were few
differences by one year. INTERPRETATION: There is insufficient evidence
supporting routine use of high dose chemotherapy with autograft for treating
early poor prognosis breast cancer.
Dupertuis YM, Meguid MM, Pichard C. (2007). "Colon cancer therapy: new perspectives
of nutritional manipulations using polyunsaturated fatty acids." Current opinions in
nutritional metabolic care 10(4): 427-32.
PURPOSE OF REVIEW: Recent advances in the development of new
therapeutic strategies combining conventional adjuvant radio/chemotherapy with
nutritional manipulations with n-3 polyunsaturated fatty acids (PUFAs) are
presented. RECENT FINDINGS: Studies in cell culture and tumour-bearing
animals have reported the ability of long-chain n-3 PUFAs to enhance the
cytotoxicity of several anticancer drugs. In colon cancer, combination of n-3
PUFAs with 5-fluorouracil resulted in an additive growth inhibitory effect on
different cell lines. Moreover, recent findings suggest that eicosapentaenoic or
docosahexaenoic acid may be used to enhance tumour radiosensitivity while
reducing mucosal/epidermal radiotoxicity similar to radioprotective agents. The
underlying mechanism is probably mediated through lipid peroxidation because
Emerging Issues228
the antitumour effect of n-3 PUFAs is shared with the n-6 PUFA, arachidonic
acid, and abolished by vitamin E. In vivo, the use of n-3 PUFAs may provide an
additional advantage compared with n-6 PUFAs. Downregulation of eicosanoid
synthesis from cyclooxygenase II may reduce angiogenesis, inflammation and
metastasis induction. SUMMARY: New insights suggest that n-3 PUFAs may
play an important role not only in cancer prevention but also in cancer
management. They may act synergistically with radio/chemotherapy to kill
tumour cells by increasing oxidative stress while reducing angiogenesis,
inflammation and metastasis induction.
Gross CP, McAvay GJ, Guo Z, Tinetti ME. (2007). "The impact of chronic illnesses on
the use and effectiveness of adjuvant chemotherapy for colon cancer." Cancer 109(12):
2410-9.
BACKGROUND: It is unclear how noncancer conditions affect the use or
effectiveness of adjuvant therapy among older patients with colon cancer.
METHODS: The authors conducted a cohort study of older patients with stage III
colon cancer who were diagnosed from 1993 to 1999 in the Surveillance,
Epidemiology, and End Results-Medicare database. The correlations between
receipt of adjuvant chemotherapy and heart failure, diabetes, and chronic
obstructive pulmonary disease (COPD) were assessed. Multivariable regression
analysis was used to assess the risk of death and hospitalization as a function of
treatment and comorbidity status. RESULTS: The study sample consisted of
5330 patients (median age, 76 years). The use of adjuvant therapy was related
significantly to heart failure (36.2% vs 64.9% of patients with vs without heart
failure, respectively; adjusted odds ratio [OR], 0.49; 95% confidence interval
[95% CI], 0.40-0.60). More moderate correlations were observed for COPD (OR,
0.83; 95% CI, 0.70-0.99) and diabetes (OR, 0.81; 95% CI, 0.68-0.97). Among
patients who had heart failure, the 5-year survival was significantly higher among
those who received adjuvant chemotherapy (adjusted 5-year survival rate, 43%;
95% CI, 40-47%) than among those who did not receive adjuvant chemotherapy
(30%; 95% CI, 27-34%). Among patients without heart failure, the 5-year survival
estimates among treated and untreated patients were 54% (95% CI, 52-56%)
and 41% (95% CI, 38-44%), respectively. The probability of all-cause, conditionspecific, or toxicity-related hospitalization associated with adjuvant therapy was
not altered by the presence of any of the 3 conditions. CONCLUSIONS: Although
chronic conditions appeared to be a strong barrier to the receipt of adjuvant
chemotherapy, adjuvant therapy appeared to provide a significant survival benefit
to patients who had colon cancer with the conditions studied.
Goyal, S., T. Kearney and B. G. Haffty (2007). "Current application and research
directions for partial-breast irradiation." Oncology (Williston Park) 21(4): 449-61;
discussion 461-2, 464, 470.
Breast-conservation therapy (BCT), consisting of lumpectomy followed by wholebreast irradiation (WBI), is the standard of care for women with early-stage
breast cancer. However, many women who are candidates for BCT either
choose mastectomy or lumpectomy alone for myriad reasons. Accelerated
Emerging Issues229
partial-breast irradiation (APBI) is a collection of radiotherapy techniques that
deliver higher daily doses of radiation to the surgical cavity with margin over a
shorter time than WBI, reducing total treatment time from 6-6.5 weeks to 1-2
weeks. Advocates of APBI state that early results of this approach demonstrate
excellent local control, minimal acute toxicity, and are associated with more
convenience for the patient. Phase III randomized clinical trials are currently
underway to assess local control, acute and chronic toxicities, and quality of life
associated with APBI compared to WBI. In this review, we hope to clarify the
rationale behind APBI and discuss in depth data concerning various partialbreast irradiation techniques that are being used throughout the United States
and around the world.
Hwang, J. J. (2007). "Role of chemotherapy in the treatment of gastroesophageal
cancers." Oncology (Williston Park) 21(5): 579-86; discussion 587, 591-2.
Esophageal, gastroesophageal junction, and gastric cancers are underpublicized
but are frequently lethal, and gastroesophageal junction adenocarcinomas are
increasingly common diseases in the United States and around the world.
Although often grouped together in studies of chemotherapy, clear distinctions
can be made in the locoregional therapy of these diseases. Esophageal
squamous cell carcinomas may be treated with surgery or radiation with
concurrent chemotherapy, whereas esophageal adenocarcinomas and
gastroesophageal junction adenocarcinomas are often treated with all three
treatment modalities. Over the past several years, it has become increasingly
evident that gastric cancer is a disease that is potentially sensitive to
chemotherapy. In the perioperative setting--at least in the Western worldchemotherapy and sometimes radiation are applied. However, the optimal
chemotherapy for advanced gastric or esophageal cancer remains unsettled, and
there is no single standard regimen. Several new chemotherapy agents have
demonstrated activity in these diseases, but the best chemotherapy remains to
be determined. This paper will review the role of chemotherapy in
gastroesophageal cancers.
Maracic, Lindy and Joanne Van Nostrand (2007). "Anesthetic implications for cancer
chemotherapy." AANA Journal 75(3): 219-226.
Cancer is one of the most prevalent disease processes affecting people of all
ages. Cancer is the second most common cause of death in the United States,
exceeded only by heart disease. Cancer survival is dependent on treatment
options that may include surgery, radiation, and chemotherapy. Chemotherapy,
or systemic cancer therapy, is designed to promote cell death during different
phases of cell growth and division. Unfortunately, chemotherapeutic agents
cannot differentiate between malignant and normal cells. Therefore, the toxic
effects of chemotherapy are also seen in healthy organs and tissues. In addition,
chemotherapeutic agents can interact with other medications. The effects of
chemotherapy may be acute and self-limiting or chronic and present long after
treatment has been completed. Patients who have had chemotherapy often
undergo surgery that may or may not be related to their cancer. Chemotherapy
Emerging Issues230
administration can have a profound influence on anesthetic management. Safe
administration of anesthesia includes knowledge of chemotherapeutic agents
and their toxic effects. This course discusses the anatomic and physiologic
effects of cancer chemotherapeutic agents and how they specifically affect
patients receiving anesthesia.
Meissner, Helen I., Robert A. Smith, Barbara K. Rimer, Katherine M. Wilson, William
Rakowski, Sally W. Vernon and Peter A. Briss (2004). "Promoting cancer screening:
Learning from experience." Cancer 101(S5): 1107-1117.
This article provides an overview of behavioral and social science cancer
screening intervention research and introduces the scope of topics addressed in
this supplement to Cancer. The authors identify and address issues to consider
before conducting interventions to promote the uptake of screening tests, such
as the benefits and harms associated with screening. Trends in the use of cancer
screening tests are discussed in the context of their efficacy and adoption over
time. Both the development and breadth of social and behavioral intervention
research intended to increase the use of effective tests are reviewed as
background for the articles that follow. The application of the lessons from this
extensive knowledge base not only should accelerate the uptake of the effective
cancer screening tests currently available, but also can guide future directions for
research. Cancer 2004. Published 2004 by the American Cancer Society.
National Cancer Institute. (2007). " The TAILORx Breast Cancer Trial." Retrieved July
7, 2007, from http://www.cancer.gov/clinicaltrials/digestpage/TAILORx.
The Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, will
examine whether genes that are frequently associated with risk of recurrence for
women with early-stage breast cancer can be used to assign patients to the most
appropriate and effective treatment.
Quah HM, Joseph R, Schrag D, Shia J, Guillem JG, Paty PB, Temple LK, Wong WD,
Weiser MR. (2007). "Young Age Influences Treatment but not Outcome of Colon
Cancer." Ann Surg oncol 26(ahead of print).
BACKGROUND: Early age at onset is often considered a poor prognostic factor
for colon cancer. The aim of this study was to determine the association between
age, clinicopathologic features, adjuvant therapy, and outcomes following colon
cancer resection. METHODS: A prospective database of 1327 surgical stage I-III
colon cancer patients operated on from 1990-2001 was evaluated, and patients
grouped by age. RESULTS: Sixty-eight patients (5%) were diagnosed at age
</=40 years (younger) compared with 1259 patients diagnosed at age >40
(older). Younger patients were more likely to have left-sided tumors (66% vs
51%, P = .02), but no more likely to present with symptomatic lesions, more
advanced tumors, or have worse pathologic features. Younger patients were
noted to have more nodes retrieved in their surgical specimens than older
patients (median 18 vs 14, P = .001), although the numbers of total colectomies
were similar in both groups. Younger patients were also more likely to receive
adjuvant chemotherapy, and this was most pronounced in the stage II cohort:
Emerging Issues231
39% vs 14%, P = .003. With a median follow-up of 55 months, 5-year diseasespecific survival (DSS) was similar in both study groups: 86% vs 87%, but 5-year
overall survival (OS) was significantly higher in the younger patient cohort (84%
vs 73%, P = .001). CONCLUSION: Younger patients undergoing complete
resection of stage I-III colon cancer had DSS similar to older patients. However,
younger patients had more nodes retrieved from their specimens and were more
likely to receive adjuvant therapy, especially for node-negative disease. These
factors may have contributed to their overall favorable outcome.
Reddy, BS. (2007). "Strategies for colon cancer prevention: combination of
chemopreventive agents." Sub-cellular biochemistry 42: 213-25.
Large bowel cancer is one of the most common human malignancies in western
countries, including North America. Several epidemiological studies have
detected decreases in the risk of colorectal cancer in individuals who regularly
use aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical trials
with NSAIDs in patients with familial adenomatous polyposis have demonstrated
that treatment with NSAIDs causes regression of pre-existing adenomas.
Preclinical efficacy studies using realistic laboratory animal models have
provided scientifically sound evidence as to how NSAIDs act to retard, block, and
reverse colonic carcinogenesis. Selective COX-2 inhibitors (celecoxib) as well as
naturally occurring anti-inflammatory agents (curcumin) have proven to be
effective chemopreventive agents against colonic carcinogenesis. There is
growing optimism for the view that realization of preventive concepts in large
bowel cancer will also serve as a model for preventing malignancies of the
prostate, the breast, and many other types of cancer. There is increasing interest
in the use of combinations of low doses of chemopreventive agents that differ in
their modes of action in order to increase their efficacy and minimize toxicity.
Preclinical studies conducted in our laboratory provide strong evidence that the
administration of combinations of chemopreventive agents (NSAIDs, COX-2
inhibitors, DFMO, statins) at low dosages inhibit carcinogenesis more effectively
and with less toxicity than when these agents are given alone.
Rendi, M. H., N. Suh, W. W. Lamph, S. Krajewski, J. C. Reed, R. A. Heyman, A.
Berchuck, K. Liby, R. Risingsong, D. B. Royce, C. R. Williams and M. B. Sporn (2004).
"The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268
cooperate to promote transforming growth factor beta-dependent apoptosis in breast
cancer." Cancer Res 64(10): 3566-71.
We show that the selective estrogen receptor modulator arzoxifene (Arz) and the
rexinoid LG100268 (268) synergize to promote apoptosis in a rat model of
estrogen receptor-positive breast carcinoma and in estrogen receptor-positive
human breast cancer cells in culture. We also show that it is not necessary to
administer Arz and 268 continuously during tumor progression to prevent cancer
in the rat model because dosing of these drugs in combination for relatively short
periods, each followed by drug-free rests, is highly effective. This new approach
to chemoprevention uses high doses of drugs that are too toxic for long-term
administration. However, when given for short periods, the agents are nontoxic
Emerging Issues232
and still induce apoptosis in breast cancer cells. We also show that the ability of
the two drugs to induce apoptosis is the combined result of induction of
transforming growth factor beta by Arz, together with inhibition of the prosurvival
nuclear factor kappaB and phosphatidylinositol 3' kinase signaling pathways by
268. The new protocol we have developed for chemoprevention allows the
efficacious and safe administration of 268 and Arz, and these agents now should
be considered for clinical use.
Riker, A. I., S. Radfar, S. Liu, Y. Wang and H. T. Khong (2007). "Immunotherapy of
melanoma: a critical review of current concepts and future strategies." Expert Opin Biol
Ther 7(3): 345-58.
Advanced melanoma is a devastating disease with a very poor overall prognosis.
There are only two agents that are approved by the FDA for use in patients with
metastatic melanoma: dacarbazine and IL-2. Both agents have an overall
response rate well below 20%, with only rare long-term responders noted.
Metastatic melanoma is known to be one of the most resistant cancers to a
plethora of treatment modalities, such as single-agent and combination
chemotherapy, chemoimmunotherapy and immunotherapy with a host of immune
stimulators. Indeed, researchers worldwide have recognized the lack of effective
therapies and have refocused their efforts on developing novel and cutting-edge
strategies of treatment. This is based on an improved understanding of the
complex interactions that occur within the tumor microenvironment, and the
central role that the host immune system plays in the surveillance of cancer. This
review summarizes the recent results of novel immunotherapeutic regimens and
focuses on cutting-edge modalities of treatment that encompass new lines of
thinking in the war against cancer and, in particular, melanoma.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Reassessing Anthracycline-Based Chemotherapy Treatment. Nancy
Ryan. Lee, NH, New Hampshire Breast Cancer Coalition.
In May 2007, the National Breast Cancer Coalition Fund (NBCCF) urged the
oncology community to “re-assess the use of anthracycline-based chemotherapy
in the adjuvant treatment of breast cancer.” (One well-known anthracycline in
breast cancer is the drug Adriamycin.) This position is based on growing
evidence that such chemotherapy may have limited value for most women and
may benefit only a small percentage of patients whose cancers “co-amplify” two
genes called Her2 and TopoII. Since anthracyclines have potentially serious side
effects, including heart toxicities and leukemia, NBCCF is calling for this
information to be peer-reviewed and published quickly.
Savellano, M. D., B. W. Pogue, P. J. Hoopes, E. S. Vitetta and K. D. Paulsen (2005).
"Multiepitope HER2 targeting enhances photoimmunotherapy of HER2-overexpressing
cancer cells with pyropheophorbide-a immunoconjugates." Cancer Res 65(14): 6371-9.
Multi-targeting strategies improve the efficacy of antibody and immunotoxin
therapies but have not yet been thoroughly explored for HER2-based cancer
treatments. We investigated multi-epitope HER2 targeting to boost
Emerging Issues233
photosensitizer immunoconjugate uptake as a way of enhancing
photoimmunotherapy. Photoimmunotherapy may allow targeted photodynamic
destruction of malignancies and may also potentiate anticancer antibodies.
However, one obstacle preventing its clinical use is the delivery of enough
photosensitizer immunoconjugates to target cells. Anti-HER2 photosensitizer
immunoconjugates were constructed from two monoclonal antibodies (mAb),
HER50 and HER66, using a novel method originally developed to label
photosensitizer immunoconjugates with the photosensitizer, benzoporphyrin
derivative verteporfin. Photosensitizer immunoconjugates were labeled instead
with a promising alternative photosensitizer, pyropheophorbide-a (PPa), which
required only minor changes to the conjugation procedure. Uptake and
phototoxicity experiments using human cancer cells were conducted with the
photosensitizer immunoconjugates and, for comparison, with free PPa. SK-BR-3
and SK-OV-3 cells served as HER2-overexpressing target cells. MDA-MB-468
cells served as HER2-nonexpressing control cells. Photosensitizer
immunoconjugates with PPa/mAb molar ratios up to approximately 10 specifically
targeted and photodynamically killed HER2-overexpressing cells. On a per mole
basis, photosensitizer immunoconjugates were less phototoxic than free PPa, but
photosensitizer immunoconjugates were selective for target cells whereas free
PPa was not. Multiepitope targeted photoimmunotherapy with a HER50 and
HER66 photosensitizer immunoconjugate mixture was significantly more
effective than single-epitope targeted photoimmunotherapy with a single antiHER2 photosensitizer immunoconjugate, provided photosensitizer
immunoconjugate binding was saturated. This study shows that multiepitope
targeting enhances HER2-targeted photoimmunotherapy and maintains a high
degree of specificity. Consequently, it seems that multitargeted
photoimmunotherapy should also be useful against cancers that overexpress
other receptors.
Schneider, SM and LE. Hood (2007). "Virtual reality: a distraction intervention for
chemotherapy." Oncology nursing Forum 34(1): 39-46.
PURPOSE/OBJECTIVES: To explore virtual reality (VR) as a distraction
intervention to relieve symptom distress in adults receiving chemotherapy
treatments for breast, colon, and lung cancer. DESIGN: Crossover design in
which participants served as their own control. SETTING: Outpatient clinic at a
comprehensive cancer center in the southeastern United States. SAMPLE: 123
adults receiving initial chemotherapy treatments. METHODS: Participants were
randomly assigned to receive the VR distraction intervention during one
chemotherapy treatment and then received no intervention (control) during an
alternate matched chemotherapy treatment. The Adapted Symptom Distress
Scale-2, Revised Piper Fatigue Scale, and State Anxiety Inventory were used to
measure symptom distress. The Presence Questionnaire and an open-ended
questionnaire were used to evaluate the subjects' VR experience. The influence
of type of cancer, age, and gender on symptom outcomes was explored. Mixed
models were used to test for differences in levels of symptom distress. MAIN
RESEARCH VARIABLES: Virtual reality and symptom distress. FINDINGS:
Emerging Issues234
Patients had an altered perception of time (p < 0.001) when using VR, which
validates the distracting capacity of the intervention. Evaluation of the
intervention indicated that patients believed the head-mounted device was easy
to use, they experienced no cyber-sickness, and 82% would use VR again.
However, analysis demonstrated no significant differences in symptom distress
immediately or two days following chemotherapy treatments. CONCLUSIONS:
Patients stated that using VR made the treatment seem shorter and that
chemotherapy treatments with VR were better than treatments without the
distraction intervention. However, positive experiences did not result in a
decrease in symptom distress. The findings support the idea that using VR can
help to make chemotherapy treatments more tolerable, but clinicians should not
assume that use of VR will improve chemotherapy-related symptoms.
IMPLICATIONS FOR NURSING: Patients found using VR during chemotherapy
treatments to be enjoyable. VR is a feasible and cost-effective distraction
intervention to implement in the clinical setting.
Sowery RD, So AI, Gleave ME. (2007). "Therapeutic options in advanced prostate
cancer: present and future." Current Urology Reports 8(1): 53-59.
Patients with advanced prostate cancer now have many treatment options
available including first- and second-line hormonal therapy, radiotherapy,
bisphosphonate therapy with zoledronic acid, and taxane-based chemotherapy.
These options now give clinicians an opportunity to offer their patients
symptomatic relief and most importantly improve overall survival. This article
reviews the current treatment options available for men with advanced prostate
cancer. In addition, novel treatment options under development, including
calcitriol, immunotherapies, small molecule inhibitors, and nucleotide-based
targeted therapy, are discussed.
Tanner, Lindsey. (2007). "Study: Chemotherapy plus surgery helps colon cancer that
has spread to liver." Fosters Online Retrieved Sunday-June-12, from
http://www.fosters.com/apps/pbcs.dll/article?AID=/20070610/FOSTERS01/106050327/1/SPNEWS02.
Warren, A. J., D. J. Mustra and J. W. Hamilton (2001). "Detection of mitomycin C-DNA
adducts in human breast cancer cells grown in culture, as xenografted tumors in nude
mice, and in biopsies of human breast cancer patient tumors as determined by (32)Ppostlabeling." Clin Cancer Res 7(4): 1033-42.
Mitomycin C (MMC) is a DNA cross-linking agent that has been used in cancer
chemotherapy for >20 years. However, little is known either qualitatively or
quantitatively about the relationship between formation and repair of specific
MMC-DNA adducts and specific biological outcomes. The goal of this study was
to examine formation and removal of specific MMC-DNA adducts in breast
cancer cells using a (32)P-postlabeling assay in relation to cytotoxicity and other
biological end points. MMC-DNA adducts were measured in cultured human
metastatic MDA-MB-435 cells, in the same cells xenografted as a mammary
tumor in nude mice, and in metastatic tumor biopsies obtained from human
Emerging Issues235
breast cancer patients undergoing MMC-based therapy. MMC adducts
corresponding to the CpG interstrand cross-link, the MMC-G bifunctional
monoadduct, and two isomers of the MMC-G monofunctional monoadduct were
detected in most samples. Despite similarities in the overall patterns of adduct
formation, there were substantial differences between the cultured cells and the
in vivo tumors in their adduct distribution profile, kinetics of adduct formation and
removal, and relationship of specific adduct levels to cytotoxicity, suggesting that
the in vivo microenvironment (e.g., degree of oxygenation, pH, activity of
oxidoreductases, and other factors) of breast cancer cells may significantly
modulate these parameters.
www.stuff.co. (2007). "Prostate cancer-the quiet killer." from
http://www.stuff.co.nz/4121925a20475.html.
Yoo, J and YJ. Lee (2007). "Effect of hyperthermia and chemotherapeutic agents on
TRAIL-induced cell death in human colon cancer cells." Journal of Cell Biochemistry
ahead of print.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
cancer therapeutic agent because of its tumor selectivity. TRAIL is known to
induce apoptosis in cancer cells but spare most normal cells. In the previous
study [Yoo and Lee, 2007], we have reported that hyperthermia could enhance
the cytotoxicity of TRAIL-induced apoptosis. We observed in human colorectal
cancer cell line CX-1 that TRAIL-induced apoptotic death and also that mild
hyperthermia promoted TRAIL-induced apoptotic death through caspase
activation and cytochrome-c release. Although its effects in vivo are not clear,
hyperthermia has been used as an adjunctive therapy for cancer. Hyperthermia
is often accompanied by chemotherapy to enhance its effect. In this study, CX-1
colorectal adenocarcinoma cells were treated with TRAIL concurrently with
hyperthermia and oxaliplatin or melphalan. To evaluate the cell death effects on
tumor cells via hyperthermia and TRAIL and chemotherapeutic agents, FACS
analysis, DNA fragmentation, and immunoblottings for PARP-1 and several
caspases and antiapoptotic proteins were performed. Activities of casapse-8,
caspase-9, and caspase-3 were also measured in hyperthermic condition.
Interestingly, when analyzed with Western blot, we detected little change in the
intracellular levels of proteins related to apoptosis. Clonogenic assay shows,
however, that chemotherapeutic agents will trigger cancer cell death, either
apoptotic or non-apoptotic, more efficiently. We demonstrate here that CX-1 cells
exposed to 42 degrees C and chemotherapeutic agents were sensitized and died
by apoptotic and non-apoptotic cell death even in low concentration (10 ng/ml) of
TRAIL. J. Cell. Biochem. (c) 2007 Wiley-Liss, Inc.
Zalcman, G., N. Richard and E. Bergot (2007). "[New biological treatments for lung
cancer]." Rev Pneumol Clin 63(1): 20-8.
Therapies targeted on cell signal pathways that control cell division and tumor
angiogenesis have been developed over the last five years for non small cell lung
cancer (NSCLC) with some amazing results, in subgroups of selected patients,
Emerging Issues236
predicting more significant success in the upcoming years. Compounds targeted
on EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3
trials including thousands of patients. Their efficacy has been proved, in second
and third line trials, after first line cisplatin-based chemotherapy for non-mucinous
adenocarcinoma in non-smokers, women and Asian patients. Response rates
vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian
patients with long survivals. Therapeutic targeting improves success rates, either
relying on EGFR gene amplification detection by FISH, or search for EGFR
tyrosine kinase domain mutations. Commercial kits are available for routine
molecular diagnosis of domain mutations potentially enabling molecular targeting
in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal
antibody to VEGF, bevacizumab, have also been developed in the last few years.
Bevacizumab associated with classical cytotoxic chemotherapy led, in selected
patients (with non squamous cell lung cancer and no past history of
cardiovascular disease) to an increase of median survival to more than 12
months with tolerable toxicity. Other drugs that have both anti-EGFR activity and
anti-angiogenic properties will be soon developed, since future bioactive anticancer drugs will probably be multi-targeted drugs.
Emerging Issues237
Surgery
Aletti, G. D., M. M. Gallenberg, W. A. Cliby, A. Jatoi and L. C. Hartmann (2007).
"Current management strategies for ovarian cancer." Mayo Clin Proc 82(6): 751-70.
Epithelial ovarian cancer originates in the layer of cells that covers the surface of
the ovaries. The disease spreads readily throughout the peritoneal cavity and to
the lymphatics, often before causing symptoms. Of the cancers unique to
women, ovarian cancer has the highest mortality rate. Most women are
diagnosed as having advanced stage disease, and efforts to develop new
screening approaches for ovarian cancer are a high priority. Optimal treatment of
ovarian cancer begins with optimal cytoreductive surgery followed by
combination chemotherapy. Ovarian cancer, even in advanced stages, is
sensitive to a variety of chemotherapeutics. Although improved chemotherapy
has increased 5-year survival rates, overall survival gains have been limited
because of our inability to eradicate all disease. Technologic advances that allow
us to examine the molecular machinery that drives ovarian cancer cells have
helped to identify numerous therapeutic targets within these cells. In this review,
we provide an overview of ovarian cancer with particular emphasis on recent
advances in operative management and systemic therapies.
Black, C., J. Marotti, E. Zarovnaya and J. Paydarfar (2006). "Critical evaluation of frozen
section margins in head and neck cancer resections." Cancer 107(12): 2792-2800.
BACKGROUND: Negative resection margins are likely the most important
prognostic factor for a patient with a head and neck squamous cell carcinoma.
Frozen-section evaluation allows a positive margin to be corrected before
surgical closure and reconstruction. A final pathology report is later issued after
examination of all resected tissues. The accuracy of the final pathology report
relies on accuracy in the preceding steps. The current process of margin
reporting in head and neck cancer resections was studied to reveal possible
waste and error in the system. METHODS: Two hundred pathologists were
surveyed about their center's current process of frozen-section margin
evaluation. The authors of the current study used the membership log of the
North American Society of Head and Neck Pathology and the list of the top 50
US cancer centers according to US News and World Report. The authors
analyzed the process of frozen-section procedure using Toyota industry
principles of quality improvement. RESULTS: The majority of surgeons send
small fragments of tissue from the surgical defect cavity. Many pathologists
receive small unoriented tissue fragments. Many resample all or most of the
margins for the final pathology report without anatomic orientation from the
surgeon. Other pathologists do not sample any margins. CONCLUSIONS: Final
margin reporting redundancy and waste is due mainly to lack of anatomic
correlation at interdisciplinary hand-offs. Oversampling and undersampling of
margins may be occurring, and the accuracy of the final pathology report may be
compromised. There is currently no consensus on how to best submit tissue for
frozen-section evaluation of head and neck resection margins
Emerging Issues238
Castillo, M. D. and P. M. Heerdt (2007). "Pulmonary resection in the elderly." Curr Opin
Anaesthesiol 20(1): 4-9.
PURPOSE OF REVIEW: With increasing longevity, altered demographics of the
lung cancer population, and preoperative interventions to enhance the efficacy of
surgical therapy, increasing numbers of elderly people will present for anesthesia
and pulmonary resection. RECENT FINDINGS: The geriatric population often
exhibits wide disparity between chronologic and physiologic senescence which is
underscored by data indicating that outcome following lung resection for cancer
is influenced more by tumor stage, preoperative functional status and
comorbidities than age alone. Nonetheless, the normal process of
cardiopulmonary aging can limit the physiological reserve necessary to
compensate for perioperative stress even in otherwise healthy elderly patients.
Data indicate a relatively favorable risk-benefit relationship for lung resection in
the elderly given the poor prognosis for patients undergoing palliative care or
chemotherapy or radiation alone. Emerging experience now suggests that
minimally invasive surgical techniques for the treatment of lung cancer may
parallel conventional thoracotomy in terms of oncologic efficacy while decreasing
perioperative morbidity in the elderly. SUMMARY: The combination of an aging
population, recent advances in neoadjuvant therapies, data supporting the
oncologic efficacy of resection, and minimally invasive surgical techniques
strongly suggests that more elderly patients will be candidates for surgical
management of their lung cancer, thus presenting anesthesiologists with unique
challenges.
Carney, P. A., M. S. Eliassen, W. A. Wells and W. G. Swartz (1998). "Can we improve
breast pathology reporting practices? A community-based breast pathology quality
improvement program in New Hampshire." J Community Health 23(2): 85-98.
We implemented a regional quality assurance program in New Hampshire (NH)
to evaluate breast pathology practices and attempt to improve the completeness
of information provided in breast surgical pathology reports. We also assessed
the degree to which NH pathologists agree with National Guidelines. The
program's objective was to promote a consistent standard of care for patients
whose breast pathology is interpreted in NH. Using a sequential survey
technique, we were able to obtain consensus on breast tissue report content that
was similar to National Guidelines. We also found that 52% of the reporting
elements improved in the post-intervention period, although only one reached
statistical significance. In conclusion, pathology interpretation is the "gold
standard" for determining both screening effectiveness and subsequent
treatment of breast cancer, yet variability in breast tissue reporting exists. It is
critical that more research be done to improve breast pathology interpretation
and reporting practices.
Emerging Issues239
Chok, KS and WL. Law (2007). "Prognostic Factors Affecting Survival and Recurrence
of Patients with pT1 and pT2 Colorectal Cancer." World journal of surgery 31(7): 148590.
BACKGROUND: Data on the prognostic factors of survival and recurrence in
patients with colorectal cancers confined to the bowel wall (T1 and T2) are
limited. The aim of the present study was to determine factors that might predict
the survival and recurrence of patients who had T1 and T2 colorectal cancers.
PATIENTS AND METHODS: All patients with T1 or T2 colorectal cancers who
underwent resection in the Department of Surgery, University of Hong Kong
Medical Centre, from 1996 to 2004 were included. Analysis was made from the
prospectively collected database. Predictive factors for lymph node metastasis
and prognostic factors were analyzed. RESULTS: A total of 265 patients (144
men) with the median age of 71 years (range: 33-93 years) were included.
Seventy-two patients had T1 cancers (rectal cancer n = 44; colon cancer n = 28;
p = 0.89) and 193 patients suffered from T2 cancer (rectal n = 120; colon cancer
n = 73). The overall incidence of lymph node metastasis was 12.7% (5.6% for T1
cancer and 14.5% for T2 cancer; p = 0.021). The presence of lymphovascular
permeation was the only independent factor associated with a higher incidence
of lymph node metastasis on multivariate analysis (odds ratio: 1.48, 95% CI:
1.44-13.47, p = 0.009). There were no significant differences in disease-free 5year survival (T1 = 84.6%; T2 = 81.1%) and 5-year cancer-specific survival in
patients with T1 and T2 tumors (T1 = 90.2%; T2 = 90.6%). Patients with lymph
node metastasis had a significantly shorter disease-free 5-year survival (p <
0.001) and 5-year cancer-specific survival (p = 0.002) when compared with those
having a negative lymph node status. Cox proportional hazards model analysis
showed that lymph node status was the only significant independent factor
predicting cancer-specific survival (hazard ratio: 3.52, 95% CI: 1.60-7.71, p =
0.002) and disease-free survival (hazard ratio: 3.42, 95% CI: 1.75-6.69, p <
0.001). CONCLUSIONS: Presence of lymphovascular permeation would have a
significant higher chance of lymph node metastasis. Positive lymph node status
was predictive of poorer survival in patients with T1 or T2 colorectal cancers. For
those cancers with positive lymphovascular permeation, radical surgery is
recommended.
Collins, E. D., C. L. Kerrigan and P. Anglade (1999). "Surgical treatment of early breast
cancer: what would surgeons choose for themselves?" Eff Clin Pract 2(4): 149-51.
CONTEXT: Although breast-conserving surgery (BCS) is less invasive than
mastectomy and results in similar survival, many women eligible for BCS
continue to undergo mastectomy. Whether the persistent use of mastectomy
means that women do not understand their options or reflects an informed
preference is unknown. OBJECTIVE: To learn which treatment surgeons would
choose when asked to imagine that they themselves had early-stage breast
cancer. DESIGN: Cross-sectional survey. SAMPLE: Convenience sample of 40
staff and resident surgeons attending surgical grand rounds at DartmouthHitchcock Medical Center in 1998. MAIN OUTCOME MEASURE: Choice of BCS
Emerging Issues240
or mastectomy for the treatment of stage I breast cancer. RESULTS: Twenty-six
male and 14 female surgeons participated in the survey. Half chose BCS and
half chose mastectomy for treatment of their hypothetical early-stage breast
cancer. Results did not differ by the sex of the surgeon. CONCLUSION: Even
after being reminded of the equivalent 10-year survival statistics, half of the
surgeons surveyed said that they would choose mastectomy over BCS for
themselves. The assumption that BCS is the "right" choice for early-stage breast
cancer may be unwarranted because many patients may have an informed
preference for mastectomy.
Dacey, Lawrence J. and David W. Johnstone (2005). "Reducing the Risk of Lung
Cancer." JAMA: Journal of the American Medical Association 294(12): 1550-1551.
Presents an editorial about reducing the risk of lung cancer. How cigarette
smoking causes about 5 million premature deaths each year; Assertion that it is
never too early or too late to stop smoking; Studies that appear in this issue
about smoking; Analysis of smoking cessation programs and what smokers can
do to decrease their risk of lung cancer.
Finlayson, S. R. (2006). "The volume-outcome debate revisited." Am.Surg. 72(11):
1038-1042.
Multiple studies support the intuitive association between higher provider
procedure volume and better clinical outcomes. Health care purchasers and
payers have been seeking ways to direct patients to high-volume providers to
improve the quality of care received and to avoid costs associated with higher
surgical morbidity. Volume-based referral has faced resistance from providers
who are concerned that the use of volume instead of more direct measures of
surgical quality will result in unfair discrimination. On close examination, volumebased referral policies also appear to be more congruent with payers' interests
than the interests of individual patients and providers. Furthermore, a policy of
volume-based referral does not address surgical quality directly, is applicable to
only a very small segment of surgical care, and is logistically problematic.
However, in the absence of viable alternative measures of surgical quality,
imperfect proxies such as volume will likely continue to be a significant part of the
national dialogue surrounding surgical quality
Katz, Steven J. and Sarah T. Hawley (2007). "From Policy To Patients And Back:
Surgical Treatment Decision Making For Patients With Breast Cancer." Health Affairs
26(3): 761-769.
Persistent use of mastectomy for breast cancer has motivated concerns about
overtreatment by surgeons and lack of patient involvement in decisions.
However, recent studies suggest that patients perceive substantial involvement
and that some patients prefer more invasive surgery, while other research
suggests that surgical treatment choices might be poorly informed. Decisionmaking quality can be improved by increasing patients' knowledge about
treatments' risks and benefits and by optimizing their involvement. The
mastectomy story underscores the limitations of utilization measures as quality
Emerging Issues241
indicators. Strategies to improve patient outcomes should focus on tools to
improve the quality of decision making and innovations in multispecialty practice.
KATZ, STEVEN J., PAULA M. LANTZ and JUDITH K. ZEMENCUK (2001). "Correlates
of Surgical Treatment Type for Women with Noninvasive and Invasive Breast Cancer."
JOURNAL OF WOMEN’S HEALTH & GENDER-BASED MEDICINE 10(7): 659-670.
There is concern that breast-conserving surgery is underused in some breast
cancer patientsub populations, including women with ductal carcinoma in situ
(DCIS), an early-stage form of the disease. We conducted a population-based
study to identify correlates of surgical treatment type and patient satisfaction,
comparing women with DCIS and those with invasive disease. We used
telephone interview and mailed survey of 183 women recently diagnosed with
breast cancer (oversampling for women with DCIS), identified from the
Metropolitan Detroit Cancer Surveillance System (response rate 71.2%). Overall,
52.5% of study subjects received a mastectomy (48.9%, 45.8%, and 73.5% of
women with DCIS, local disease, and regional disease, respectively, p , 0.05).
One third of women did not perceive that they were given a choice between
surgical types, and an additional one third of women received a surgeon
recommendation, most of whom received the treatment recommended. Patient
attitudes, such as concerns about the clinical benefits and risks of specific
surgery options, were important correlates of treatment choice but did not vary by
stage of disease. Knowledge about differences in clinical benefits and risks
between surgery options was low. Finally, satisfaction with the decision-making
process was significantly lower in women who did not perceive a choice between
surgery options. Correlates of breast cancer surgery type appeared to be similar
for women with DCIS and invasive breast cancer, with surgeons playing a
dominant role in the process. Results also suggested that the decision-making
process may be as important for patient satisfaction as the treatment chosen.
Kauff, Noah D. and Kenneth Offit (2007). Modeling Genetic Risk of Breast Cancer.
JAMA: Journal of the American Medical Association: 2637-2639.
This article presents an editorial on the modeling of the genetic risk of breast
cancer. Models predicting the likelihood of getting breast cancer have been used
to determine eligibility for screening and prevention trials and in risk-reducing
strategies. A study in this issue shows a limitation of genetic risk assessment
modeling and suggests that the models must be refigured. Shortcomings of the
available models are presented.
McBride, Deborah (2007). "Second Opinion May Change Breast Cancer Treatment."
ONS Connect 22(3): 7-7.
The article discusses research being done on the importance of second opinion
to breast cancer patients. It references a study by E. A. Newman et al published
in a 2006 issue of "Cancer." The study author states that getting a second
opinion from a team of specialists results in a significant change in the
recommended surgical treatment in more than half of the cases of newly
diagnosed breast cancer.
Emerging Issues242
Naspinsky, S. and A. Siegel (2005). "Chondroblastoma metastasis to lung visualized on
bone scan." Clin.Nucl.Med. 30(2): 110-111.
Passage, K. J. and N. J. McCarthy (2007). "Critical review of the management of earlystage breast cancer in elderly women." Intern Med J 37(3): 181-9.
The treatment of elderly women (> or =70 years) with early-stage breast cancer
is an emerging clinical problem in the setting of an ageing population. There is a
lack of clinical trial evidence to formulate clinical guidelines for management
because of the small number of elderly women included in previous clinical trials
of adjuvant therapy. This often results in elderly patients being denied standard
management based on age alone. The often-complex interaction between age,
comorbid conditions and function complicate the planning and outcomes of
surgery and can have an effect on the delivery of postoperative adjuvant therapy.
A comprehensive assessment of the elderly patient is essential to determine
overall prognosis and morbidity risk from treatments; however, a simple
comorbidity scale for use in routine clinical practice remains elusive. Thus,
treatment decisions should be tailored to the individual to ensure that therapies
are not unduly withheld and are appropriate for the patient's overall condition.
The assessment of the elderly patient with breast cancer requires the
involvement of a multidisciplinary team. The evidence for efficacy, safety and
potential risks of surgery and adjuvant therapies (including radiotherapy,
hormone therapy and chemotherapy) in the elderly population is discussed in this
review and the role of comprehensive geriatric assessment is outlined.
Rainsbury, R. M. (2003). "Training and skills for breast surgeons in the new millennium."
ANZ J Surg 73(7): 511-6.
Breast surgeons are learning to adapt to an evidence-based, guideline-directed
and outcome-orientated culture as key members of the multidisciplinary team.
Recent data has confirmed the central role of surgery in preventing recurrence,
improving survival and reducing risk, and rising scrutiny is raising the standards
of breast cancer treatment. Specialization is increasing in breast surgery as a
result of foreshortened training, greater patient demand and increasing trainee
expectations and breast surgeons are learning new skills. The balance of the
breast surgeon's skill-base reflects personal preferences and professional
networks, local needs and geographical -constraints, and current developments
in advanced surgical training curricula. Modern training programmes need to
recognize these needs, supporting interprofessional cross-specialty training
initiatives and encouraging professional development. Trainees and -trainers will
need to acquire new skills in diagnostic, targeted, oncoplastic and prophylactic
procedures through a variety of new training initiatives. Breast surgery is
standing on the threshold of change, and breast surgeons must develop new
strategies, new skills and new alliances to strengthen their role in this expanding
specialty.
Rainsbury, R. M. (2006). "Skin-sparing mastectomy." Br J Surg 93(3): 276-81.
Emerging Issues243
BACKGROUND: Skin-sparing mastectomy (SSM) is a new technique being used
in a variety of clinical settings. This article reviews the published data on SSM to
establish its current role in clinical practice. METHODS: A Medline search was
carried out using the key words 'skin-sparing mastectomy' to identify Englishlanguage articles published between 1990 and 2004 and further material
referenced in these publications. RESULTS: SSM is most commonly used for
surgical prophylaxis and to treat in situ and early invasive disease in patients who
request immediate breast reconstruction. SSM and non-SSM result in similar
surgical and oncological outcomes, but skin flap ischaemia is more common after
SSM and is associated with a range of risk factors, including smoking.
CONCLUSION: SSM has become an established procedure in breast surgery,
but there is a lack of prospective data on which to make evidence-based
decisions about its use in individual patients.
Stanciu C, Trifan A, Khder SA. (2007). "Accuracy of colonoscopy in localizing colonic
cancer."
t is important to establish the precise localization of colonic cancer
preoperatively; while colonoscopy is regarded as the diagnostic gold standard for
colorectal cancer, its ability to localize the tumor is less reliable. AIM: To define
the accuracy of colonoscopy in identifying the location of colonic cancer.
METHODS: All of the patients who had a colorectal cancer diagnosed by
colonoscopy at the Institute of Gastroenterology and Hepatology, Iaşi and
subsequently received a surgical intervention at three teaching hospitals in Iaşi,
between January 2001 and December 2005, were included in this study.
Endoscopic records and operative notes were carefully reviewed, and tumor
localization was recorded. RESULTS: There were 161 patients (89 men, 72
women, aged 61.3 +/- 12.8 years) who underwent conventional surgery for colon
cancer detected by colonoscopy during the study period. Twenty-two patients
(13.66%) had erroneous colonoscopic localization of the tumors. The overall
accuracy of preoperative colonoscopic localization was 87.58%.
CONCLUSIONS: Colonoscopy is an accurate, reliable method for locating colon
cancer, although additional techniques (i.e., endoscopic tattooing) should be
performed at least for small lesions.
Stelzer, Keith J. (2004). "Breast surgery in the ‘Arimidex, Tamoxifen alone or in
combination’ (ATAC) trial: American women are more likely than women from the
United Kingdom to undergo mastectomy." Women’s Oncol Rev 2004 4: 305-306.
Objective: To evaluate factors that affect the decision to undergo mastectomy vs.
conservation therapy in a large multinational trial of adjuvant therapy in patients
with operable breast cancer.
Tanner, Lindsey. (2007). "Study: Chemotherapy plus surgery helps colon cancer that
has spread to liver." Fosters Online Retrieved Sunday-June-12, from
http://www.fosters.com/apps/pbcs.dll/article?AID=/20070610/FOSTERS01/106050327/1/SPNEWS02.
Emerging Issues244
Wells, W. A., P. A. Carney, M. S. Eliassen, A. N. Tosteson and E. R. Greenberg (1998).
"Statewide study of diagnostic agreement in breast pathology." J Natl Cancer Inst 90(2):
142-5.
BACKGROUND: This study assessed the degree of diagnostic agreement
among community-based general pathologists reading slides of representative
breast tissue specimens and tested whether diagnostic variability is associated
with type of breast specimen (e.g., core needle or excisional biopsy) or slide
quality. METHODS: Twenty-six of the 44 eligible pathologists working at
community-based pathology practices in New Hampshire participated. Each
pathologist evaluated slides of breast tissue obtained from 30 case subjects
randomly selected from a statewide breast pathology database. The diagnostic
categories used were benign, benign with atypia, noninvasive malignant, and
invasive malignant. The levels of agreement (i.e., kappa coefficients) for the
diagnoses were assessed. RESULTS: Agreement was high among pathologists
for assignment of diagnostic category (kappa coefficient = 0.71) and was nearly
perfect for their selection of benign versus malignant categories (kappa
coefficient = 0.95). There was less agreement for the categories of noninvasive
malignant and benign with atypia (kappa coefficients of 0.59 and 0.22,
respectively). There was no apparent relationship between levels of diagnostic
agreement and specimen type or perceived slide quality. CONCLUSIONS:
Diagnostic agreement for breast tissue specimens is high overall among
community-based pathologists, but clinically relevant disagreements may occur
in the assessment of noninvasive malignant diagnoses. The establishment of
reread policies for certain diagnostic categories may reduce the possibility that
diagnostic misclassification will lead to overtreatment or undertreatment. The
high degree of diagnostic reproducibility for invasive cancerous lesions of the
breast suggests that it is unnecessary for a central review of these lesions in
national cancer trials.
Yao, M., J. B. Epstein, B. J. Modi, K. B. Pytynia, A. J. Mundt and L. E. Feldman (2007).
"Current surgical treatment of squamous cell carcinoma of the head and neck." Oral
Oncol 43(3): 213-23.
Historically treatment of head and neck cancers involved surgical resection
followed by radiation therapy for advanced tumors. Concurrent chemoradiation
therapies have shown equal survival to surgical resection with better preservation
of function. However, concurrent therapy does entail significant morbidity, and
recent advances have been used to minimize that morbidity. Newer tumor
specific medical therapies are anticipated to be less toxic while maintaining a
high degree of efficacy. For resectable cancer, transoral laser microsurgery is a
new trend in surgery for complete resection of tumors with preservation of
function. Advanced reconstructive techniques that allow free transfer of soft
tissue and bone from all over the body improve the functional and aesthetic
outcomes following major ablative surgery. With successful surgical
reconstruction, dental and prosthetic rehabilitation choices are enhanced.
Advances in rehabilitation of speech following removal of the larynx have
improved the quality of life post-laryngectomy patients. With these newer
Emerging Issues245
therapies and methods of reconstruction, each patient needs to be carefully
evaluated to maximize the possibility of cure and level of function, and minimize
the morbidity associated with treatment. Combined chemotherapy and radiation
protocols are associated with increased acute and chronic toxicities that may
affect the quality of life due to the impact upon oral disease and oral function.
Oral care providers must be aware of advances in cancer management and
implications for patient care to effectively care for these patients.
Zakaria, S. and A. C. Degnim (2007). "Prophylactic mastectomy." Surg Clin North Am
87(2): 317-31, viii.
With availability of genetic testing and development of statistical models for risk
stratification, more women are being identified as having increased risk for breast
cancer. A number of risk-reducing treatment options with varying efficacy exist
for them, including frequent surveillance, chemoprevention, prophylactic
salpingo-oophorectomy (PSO), and prophylactic mastectomy (PM). Those most
likely to benefit from PM are BRCA gene carriers and those who have a strong
family history of breast cancer. Prevetive PM remains controversial, however.
There are no randomized controlled trials to substantiate the potential benefit or
harms of PM. This article describes the high-risk women in whom PM may be
considered, and summarizes data on the efficacy of PM as a treatment for the
prevention of breast cancer.
Emerging Issues246
Alternative Therapies
"Integrative oncology: complementary therapy for cancer survivors." (2007). J Support
Oncol 5(2): 74-5.
Cheetham, P. J., K. J. Le Monnier and S. F. Brewster (2001). "Attitudes and use of
alternative therapies in UK prostate cancer patients-isn't it time we were in the know?"
Prostate Cancer Prostatic Dis 4(4): 235-241.
With increasing media interest in prostate cancer and the availability of data to
patients from support groups and the Internet, the knowledge and use of
alternative therapies by patients is becoming more common. The purpose of our
study was to quantify patient awareness and use of alternative therapies for the
prevention and treatment of prostate cancer in the UK. In May 2000, we
performed a survey of men attending our urology outpatient clinic for prostate
cancer evaluation or follow-up. All men diagnosed with and those at high risk
(abnormal prostate specific antigen) for prostate cancer were eligible for the
study. Each eligible patient was then sent an anonymous 25-item questionnaire
to explore their knowledge and use of various alternative therapies for prostate
cancer. Out of 195 patients who were sent the questionnaire, 168 responded, for
a response rate of 86%. One hundred and sixty-four were analysed. Eight-two
out of 164 (50%) were aware of alternative therapies for prevention/treatment of
prostate cancer, the most common were tomatoes/tomato-based products and
low-fat diet. There were 27 (16.5%) respondents taking alternative therapies for
their prostate. Private patients were more aware (60.4% private vs 46.2% NHS)
of complimentary therapies and were more likely to take them (27.9% private vs
12.4% NHS) than National Health Service patients. The majority of patients
(60%) had not informed their GP or urologist. Fifteen therapies and 12
medication sources were recorded. Asked if doctors should discuss nonprescribed therapies, even if there is no proven benefit, 62% said 'yes' while 29%
said 'no'. Alternative therapy use for prostate cancer is likely to increase. If we
don't ask patients specifically whether they are taking them, patients are unlikely
to tell us. Urologists and clinical oncologists treating men with prostate cancer
need to be aware of alternative therapies and have some understanding of any
benefit or harm, not only to be able to answer patient's questions and offer
advice, but also to consider interactions with other treatments.Prostate Cancer
and Prostatic Diseases (2001) 4, 235-241.
DiGianni, Lisa M., Judy E. Garber and Eric P. Winer (2002). "Complementary and
Alternative Medicine Use Among Women With Breast Cancer." J Clin Oncol
20(suppl_1): 34s-38.
Abstract: Complementary and alternative medicine (CAM) use has increased in
recent years, with at least 42% of individuals in the United States using some
form of CAM in 1997. CAM includes a variety of modalities, ranging from
nutritionally based interventions to behavioral techniques. This article reviews the
status of CAM use among women with breast cancer. Patients are increasingly
incorporating CAM into cancer prevention and treatment regimens. The
Emerging Issues247
prevalence of CAM use by breast cancer patients varies; however, it is typically
higher than among individuals in the general population. Commonly used CAMs
among women with breast cancer include nutritional/dietary supplements,
relaxation strategies, and various types of social support groups. Apart from
psychosocial interventions, little scientific evidence exists regarding the efficacy
of CAM use for breast cancer patients. A common theme seen in many studies is
that CAM use in women with breast cancer is highly correlated with increased
psychosocial distress.
Dragnev, K. H., J. R. Rigas and E. Dmitrovsky (2000). "The retinoids and cancer
prevention mechanisms." Oncologist 5(5): 361-8.
Carcinogenesis is a multistep process that converts normal cells into malignant
cells. Once transformed, malignant cells acquire the ability to invade and
metastasize, leading to clinically evident disease. During this continuum from
normal to metastatic cells, carcinogenic steps can be arrested or reversed
through pharmacological treatments, known as cancer chemoprevention.
Chemoprevention strategies represent therapeutic interventions at early stages
of carcinogenesis, before the onset of invasive cancer. Effective
chemoprevention should reduce or avoid the clinical consequences of overt
malignancies by treating early neoplastic lesions before development of clinically
apparent signs or symptoms. Preclinical, clinical, and epidemiological data
provide considerable support for cancer chemoprevention as an attractive
therapeutic strategy. This clinical approach was validated in the recent tamoxifen
randomized trial, demonstrating that a selective estrogen receptor modulator
reduces the risk of breast cancer in women at high risk for this malignancy.
Derivatives of vitamin A, the retinoids, have reported activity in treating specific
premalignant lesions and reducing incidence of second primary tumors in
patients with prior head and neck, lung or liver cancers. Whether the retinoids will
prevent primary cancers at these sites is not yet known. Notably, a carotenoid
(beta-carotene) was shown as inactive in primary prevention of lung cancers in
high-risk individuals. This underscores the need for relevant in vitro models to
identify pathways signaling chemopreventive effects. These models should
assess the activity of candidate chemoprevention agents before the conduct of
large and costly prevention trials. An improved understanding of cancer
prevention mechanisms should aid in the discovery of new therapeutic targets
and chemoprevention agents. Ideally, these agents should have tolerable clinical
toxicities suitable for chronic administration to individuals at high risk for
developing primary or second cancers. This article reviews what is now known
from clinical and preclinical studies about the retinoids as cancer prevention
agents.
Hyodo, I., N. Amano, K. Eguchi, M. Narabayashi, J. Imanishi, M. Hirai, T. Nakano and
S. Takashima (2005). "Nationwide survey on complementary and alternative medicine
in cancer patients in Japan." J Clin Oncol 23(12): 2645-54.
PURPOSE: To determine the prevalence of use of complementary and
alternative medicine (CAM) by patients with cancer in Japan, and to compare the
Emerging Issues248
characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A
questionnaire on cancer CAM and the Hospital Anxiety and Depression Scale
were delivered to 6,607 patients who were treated in 16 cancer centers and 40
palliative care units. RESULTS: There were 3,461 available replies for a
response rate of 52.4%. The prevalence of CAM use was 44.6% (1,382 of 3,100)
in cancer patients and 25.5% (92 of 361) in noncancer patients with benign
tumors. Multiple logistic regression analysis determined that history of
chemotherapy, institute (palliative care units), higher education, an altered
outlook on life after cancer diagnosis, primary cancer site, and younger age were
strongly associated with CAM use in cancer patients. Most of the CAM users with
cancer (96.2%) used products such as mushrooms, herbs, and shark cartilage.
The motivation for most CAM use was recommendation from family members or
friends (77.7%) rather than personal choice (23.3%). Positive effects were
experienced by 24.3% of CAM users with cancer, although all of them received
conventional cancer therapy concurrently. Adverse reactions were reported by
5.3% of cancer patients. CAM products were used without sufficient information
by 57.3% of users with cancer and without a consultation with a doctor by 60.7%
of users. CONCLUSION: This survey revealed a high prevalence of CAM use
among cancer patients, without sufficient information or consultation with their
physicians. Oncologists should not ignore the CAM products used by their
patients because of a lack of proven efficacy and safety.
Michaud, L. B., J. P. Karpinski, K. L. Jones and J. Espirito (2007). "Dietary supplements
in patients with cancer: risks and key concepts, part 1." Am J Health Syst Pharm 64(4):
369-81.
PURPOSE: The risks and key concepts regarding the use of dietary supplements
in patients with cancer are described. SUMMARY: There are six common
characteristics of dietary supplements that must be addressed when used by
patients with cancer. Clinicians must establish if the supplement is an
antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or
immunomodulating properties, has hormonal properties, has known safety
issues, and has known or theoretical drug interactions. These six characteristics
of the dietary supplements commonly used by patients with cancer are reviewed
to aid in the analysis of the scientific data and communication of the results with
the patient or family members. A framework upon which clinicians can
adequately help patients make informed decisions regarding the use of
complimentary and alternative medicine and dietary supplements is also
described. When evaluating the appropriateness of a supplement for use by a
patient with cancer, clinicians must conduct a safety review (evaluate the six
characteristics). If the supplement is considered safe, an efficacy review must be
conducted, after which the clinicians can recommend the supplement's use,
accept the patient's decision to use the supplement if no or inconclusive evidence
exists, or discourage use if there is conclusive evidence supporting inefficacy.
Available resources for locating information regarding dietary supplements are
also discussed. CONCLUSION: Counseling patients with cancer about dietary
Emerging Issues249
supplements requires a systematic thought process that considers the available
theories and data, as well as the patients' views about the agents.
Michaud, L. B., J. P. Karpinski, K. L. Jones and J. Espirito (2007). "Dietary supplements
in patients with cancer: risks and key concepts, part 2." Am J Health Syst Pharm 64(5):
467-80.
PURPOSE: The risks and key concepts regarding the use of dietary supplements
in patients with cancer are described. SUMMARY: There are six common
characteristics of dietary supplements that must be addressed when used by
patients with cancer. Clinicians must establish if the supplement is an
antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or
immunomodulating properties, has hormonal properties, has known safety
issues, and has known or theoretical drug interactions. These six characteristics
of the dietary supplements commonly used by patients with cancer are reviewed
to aid in the analysis of the scientific data and communication of the results with
the patient or family members. A framework upon which clinicians can
adequately help patients make informed decisions regarding the use of
complimentary and alternative medicine and dietary supplements is also
described. When evaluating the appropriateness of a supplement for use by a
patient with cancer, clinicians must conduct a safety review (evaluate the six
characteristics). If the supplement is considered safe, an efficacy review must be
conducted, after which the clinicians can recommend the supplement's use,
accept the patient's decision to use the supplement if no or inconclusive evidence
exists, or discourage use if there is conclusive evidence supporting inefficacy.
Available resources for locating information regarding dietary supplements are
also discussed. CONCLUSION: Counseling patients with cancer about dietary
supplements requires a systematic thought process that considers the available
theories and data, as well as the patients' views about the agents.
Navo, Marisa A., Julie Phan, Christy Vaughan, J. Lynn Palmer, Laura Michaud, Kellie L.
Jones, Diane C. Bodurka, Karen Basen-Engquist, Gabriel N. Hortobagyi, John J.
Kavanagh and Judith A. Smith (2004). "An Assessment of the Utilization of
Complementary and Alternative Medication in Women with Gynecologic or Breast
Malignancies." J Clin Oncol 22(4): 671-677.
PURPOSE: To describe and assess the current utilization of complementary and
alternative medicines (CAMs) in women with a diagnosis of either gynecologic or
breast cancer and evaluate their reasons for use. PATIENTS AND METHODS:
This study included 250 female patients from the Multidisciplinary Breast Center
and 250 patients from the Gynecologic Oncology Center of The University of
Texas M.D. Anderson Cancer Center (Houston, TX). Patients were selected by
having an odd-numbered medical record number, and they were contacted
before their clinic visit. The goals of the study were explained, and verbal consent
was obtained. Patients who agreed to participate were asked to bring a written
list and the medication bottles of all over-the-counter prescriptions and CAMs
with them to clinic. In clinic, the investigator obtained a written informed consent
and administered the survey. All patients and surveys were assessable.
Emerging Issues250
RESULTS: The most frequently used herbal products and
megavitamins/minerals were identified from the patient medication histories.
Overall, we found the proportion of patients using CAM to be 48% (95% CI, 44%
to 53%; 241 of 500 patients). CAM use was related to patients' educational
status: 62% had postgraduate degrees, 50% had college degrees, 56% had
some college, and 33% had a high school education or less. Also, among
patients using CAMs, only 53.5% had spoken to a healthcare provider regarding
CAM therapy. CONCLUSION: The use of CAM is common among women with
cancer. Studies need to be conducted to establish if there are any potential drug
interactions and/or therapeutic benefit of CAM products. Moreover, there is a
need to educate patients and healthcare providers on appropriate and safe use
of CAM products.
Treasure, Jonathan. (2005). "Food, Medicine, Poison & "Molecular Vitalism"."
Retrieved 6/25/2007, from http://www.herbological.com/cancerandherbalmed.html.
The author describes the use of herbal medical treatments in the fight against
cancer. The connection between the effect of dietary and naturally occurring
elements and the reduction or control of cancer cells is explored.
Winquist, E., T. Waldron, S. Berry, D. S. Ernst, S. Hotte and H. Lukka (2006). "Nonhormonal systemic therapy in men with hormone-refractory prostate cancer and
metastases: a systematic review from the Cancer Care Ontario Program in Evidencebased Care's Genitourinary Cancer Disease Site Group." BMC Cancer 6: 112.
BACKGROUND: Prostate cancer that has recurred after local therapy or
disseminated distantly is usually treated with androgen deprivation therapy;
however, most men will eventually experience disease progression within 12 to
20 months. New data emerging from randomized controlled trials (RCTs) of
chemotherapy provided the impetus for a systematic review addressing the
following question: which non-hormonal systemic therapies are most beneficial
for the treatment of men with hormone-refractory prostate cancer (HRPC) and
clinical evidence of metastases? METHODS: A systematic review was performed
to identify RCTs or meta-analyses examining first-line non-hormonal systemic
(cytotoxic and non-cytotoxic) therapy in patients with HRPC and metastases that
reported at least one of the following endpoints: overall survival, disease control,
palliative response, quality of life, and toxicity. Excluded were RCTs of secondline hormonal therapies, bisphosphonates or radiopharmaceuticals, or
randomized fewer than 50 patients per trial arm. MEDLINE, EMBASE, the
Cochrane Library, and the conference proceedings of the American Society of
Clinical Oncology were searched for relevant trials. Citations were screened for
eligibility by four reviewers and discrepancies were handled by consensus.
RESULTS: Of the 80 RCTs identified, 27 met the eligibility criteria. Two recent,
large trials reported improved overall survival with docetaxel-based
chemotherapy compared to mitoxantrone-prednisone. Improved progression-free
survival and rates of palliative and objective response were also observed.
Compared with mitoxantrone, docetaxel treatment was associated with more
frequent mild toxicities, similar rates of serious toxicities, and better quality of life.
Emerging Issues251
More frequent serious toxicities were observed when docetaxel was combined
with estramustine. Three trials reported improved time-to-disease progression,
palliative response, and/or quality of life with mitoxatrone plus corticosteroid
compared with corticosteroid alone. Single trials reported improved disease
control with estramustine-vinblastine, vinorelbine-hydrocortisone, and suraminhydrocortisone compared to controls. Trials of non-cytotoxic agents have
reported equivocal results. CONCLUSION: Docetaxel-based chemotherapy
modestly improves survival and provides palliation for men with HRPC and
metastases. Other than androgen deprivation therapy, this is the only other
therapy to have demonstrated improved overall survival in prostate cancer in
RCTs. Further investigations to identify more effective therapies for HRPC
including the use of systemic therapies earlier in the natural history of prostate
cancer are warranted.
Emerging Issues252
Other Emerging Issues in Cancer Treatment
Anderson, K. C. (2007). "Targeted therapy of multiple myeloma based upon tumormicroenvironmental interactions." Exp Hematol 35(4 Suppl 1): 155-62.
Multiple myeloma (MM) remains incurable, but recent advances in genomics and
proteomics have allowed for advances in our understanding of disease
pathogenesis, identified novel therapeutic targets, allowed for molecular
classification, and provided the scientific rationale for combining targeted
therapies to increase tumor cell cytotoxicity and abrogate drug resistance.
Besides these advances, recognition of the role of the bone marrow (BM) milieu
in conferring growth, survival, and drug resistance in MM cells, both in laboratory
and animal models, has allowed for the establishment of a new treatment
paradigm targeting the tumor cell and its microenvironment to overcome drug
resistance and improve patient outcomes in MM. In particular, thalidomide,
bortezomib, and lenalidamide all overcome conventional drug resistance, not
only by directly inducing tumor cell cytotoxicity, but by inhibiting adhesion of MM
cells to BM. This abrogates constitutive and MM-binding-induced transcription
and secretion of cytokines, inhibits angiogenesis, and augments host anti-MM
immunity. These three drugs have rapidly translated from bench to bedside and
in treatment protocols of MM, first in patients with relapsed refractory disease,
and then alone and in combination in newly diagnosed patients. Promising novel
targeted agents include the novel proteasome inhibitor NPI-0052 and the heat
shock protein inhibitor KOS-953. Importantly, gene-array, proteomic, and cellsignaling studies have not only helped to identify in vivo mechanisms of action
and drug resistance to novel agents, but also aided in the design of promising
combination-therapy protocols.
Ayash, L. J., V. Ratanatharathorn, T. Braun, S. M. Silver, C. M. Reynolds and J. P.
Uberti (2007). "Unrelated donor bone marrow transplantation using a chemotherapyonly preparative regimen for adults with high-risk acute myelogenous leukemia." Am J
Hematol 82(1): 6-14.
Limited data are available for adults undergoing unrelated donor (URD) BMT for
AML using chemotherapy-only preparative regimens. Previous studies
incorporated irradiation, included adults and children, and excluded secondary
leukemia. Herein we report long-term outcomes for adults with poor-prognostic
AML receiving a novel regimen of busulfan (16 mg/kg), cytarabine (8,000
mg/m(2)), and cyclophosphamide (120 mg/kg) (BAC), followed by URD BMT.
From June 1995 through October 2001, 45 adults were enrolled. Adverse
features included unfavorable cytogenetics (49%), secondary AML (47%),
leukemia at transplant (42%), and extramedullary disease (16%). At time of BMT,
23 were in remission (12 CR1) while 22 had leukemia. Four (9%) died early.
Acute and chronic GVHD rates were 44 and 67%, respectively. Seventeen (38%)
were disease-free 52 months post-BMT; 13 were leukemia-free (eight CR1) at
transplant. Eleven relapsed. Three-year DFS and OS were 42 and 46%,
respectively. DFS and OS were longer, and relapses less, for those in CR at time
Emerging Issues253
of BMT. Secondary leukemia, cytogenetics, cell dose, and GVHD did not
influence outcome. In poor-risk AML, BAC provided cytoreduction comparable to
reported TBI-containing regimens, when administered for URD BMT. With
decreasing treatment-related mortality, it is justified to proceed early to URD BMT
for patients with poor prognostic features.
Bioresearch online. (2007). "Fat Kills Cancer: Turning Stem Cells From Fat Tissue Into
Personalized, Cancer-Targeted Therapeutics." from
http://www.bioresearchonline.com/content/news/article.asp?docid=f7836148-dbd44580-85ca-c4922aeec83f&atc~c=771+s=773+r=001+l=a&VNETCOOKIE=NO.
Eapen, M., P. Rubinstein, M. J. Zhang, C. Stevens, J. Kurtzberg, A. Scaradavou, F. R.
Loberiza, R. E. Champlin, J. P. Klein, M. M. Horowitz and J. E. Wagner (2007).
"Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow
in children with acute leukaemia: a comparison study." Lancet 369(9577): 1947-54.
BACKGROUND: Although umbilical cord blood is an accepted alternative to
bone marrow for transplantation, allele-matched bone marrow is generally
regarded as the preferred graft source. Our aim was to assess leukaemia-free
survival after transplantations of these alternatives compared with present HLAmatching practices, and to assess the relative effect of cell dose and HLA match,
and their potential interaction on leukaemia-free survival after cord-blood
transplantation. METHODS: Outcomes of 503 children (<16 years) with acute
leukaemia and transplanted with umbilical cord blood were compared with
outcomes of 282 bone-marrow recipients. All transplantation took place in the
USA. Recipients of umbilical cord blood were transplanted with grafts that were
HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens
(n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLADRB1). Bone-marrow recipients were transplanted with grafts that were matched
at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or
mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival.
FINDINGS: In comparison with allele-matched bone-marrow transplants, 5-year
leukaemia-free survival was similar to that after transplants of umbilical cord
blood mismatched for either one or two antigens and possibly higher after
transplants of HLA-matched umbilical cord blood. Transplant-related mortality
rates were higher after transplants of two-antigen HLA-mismatched umbilical
cord blood (relative risk 2.31, p=0.0003) and possibly after one-antigen HLAmismatched low-cell-dose umbilical-cord-blood transplants (1.88, p=0.0455).
Relapse rates were lower after two-antigen HLA-mismatched umbilical-cordblood transplants (0.54, p=0.0045). INTERPRETATION: These data support the
use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord
blood in children with acute leukaemia who need transplantation. Because better
HLA matching and higher cell doses significantly decrease the risk of transplantrelated mortality after umbilical-cord-blood transplantation, greater investment in
large-scale banking is needed to increase HLA diversity.
Emerging Issues254
Houghton, J. (2007). "Bone-marrow-derived cells and cancer--an opportunity for
improved therapy." Nat Clin Pract Oncol 4(1): 2-3.
Hwang, W. Y., M. Samuel, D. Tan, L. P. Koh, W. Lim and Y. C. Linn (2007). "A metaanalysis of unrelated donor umbilical cord blood transplantation versus unrelated donor
bone marrow transplantation in adult and pediatric patients." Biol Blood Marrow
Transplant 13(4): 444-53.
Several studies have compared the results of unrelated donor bone marrow
transplantation (UBMT) and unrelated donor cord blood transplantation (UCBT).
To objectively analyze these data, we performed a systematic review and metaanalysis of pooled data on comparative studies of UCBT and UBMT in patients
requiring hematopoietic stem cell transplantation. Combining the studies, 161
children and 316 adults undergoing UCBT (mostly 1 or 2 antigen-mismatched),
along with 316 children and 996 adults undergoing UBMT (almost entirely fully
matched with the recipient), were analyzed. T-cell-depleted UBMT was excluded;
where data were available, only fully matched UBMT was used in the analysis.
Pooled comparisons of studies of UCBT and UBMT in children found that the
incidence of chronic graft-versus-host disease (GVHD) was lower with UCBT
(relative risk [RR] = 0.26; 95% confidence interval [CI] = 0.12-0.57; P = .16), but
the incidence of grade III-IV acute GVHD did not differ (RR = 1.46; 95% CI =
0.42-5.03; P = .55). There was no difference in 2-year OS in children when
studies were pooled (RR = 0.76; 95% CI = 0.31-1.87; P = .55). For adults,
transplantation-related mortality (pooled estimate, 1.04; 95% CI = 0.52-2.08; P =
.91) and disease-free survival (DFS) (pooled estimate, 0.59; 95% CI = 0.18-1.96;
P = .39) were not statistically different. Because of the unavailability of
randomized controlled trials, pooled analysis of nonrandomized comparative
studies was performed. Thus, our meta-analysis confirmed that UCBT in children
and adults had consistently equivalent survival outcomes compared with UBMT
despite greater donor-recipient HLA disparity with UCBT.
Kasamon, Y. L. (2007). "Blood or marrow transplantation for mantle cell lymphoma."
Curr Opin Oncol 19(2): 128-35.
PURPOSE OF REVIEW: Mantle cell lymphoma is a generally incurable disease
for which blood or marrow transplantation is frequently considered. This review
assesses the more recent literature on high-dose therapeutic approaches for
mantle cell lymphoma. RECENT FINDINGS: The benefit of transplantation is
most apparent in first remission. Autologous transplantation can prolong eventfree and possibly overall survival, although no plateau has been demonstrated in
the survival curve. A randomized controlled trial demonstrated a significant
event-free survival advantage to upfront autologous transplantation compared
with interferon maintenance. The relative merit of autologous versus allogeneic
transplantation remains to be better defined. SUMMARY: The role of
transplantation for mantle cell lymphoma is controversial, as the impact on
overall survival is unclear. Transplantation should be considered early in the
disease course. Elimination of minimal residual disease through in-vivo purging
of stem cells may translate into more durable remissions. Nonmyeloablative
Emerging Issues255
allogeneic transplantation and high-dose radioimmunotherapy are topics of
ongoing investigation.
Maurer, L. H., T. Davis, S. Hammond, E. Smith, P. West and M. Doolittle (2001).
"Clinical trials in a rural population: professional education aspects." J Cancer Educ
16(2): 89-92.
BACKGROUND: While the majority of cancer patients in rural New Hampshire
and Vermont are treated in community hospitals, few have entered clinical trials.
This report describes a rural hospital consortium as a single Cancer and
Leukemia Group B (CALGB) affiliate that used local cancer teams and itinerant
oncologists to develop a clinical trials program. METHOD: Grafted onto an
existing oncology outreach program, educational programs were developed to
help identify patients and recruit them to cooperative group clinical trials.
Outcomes included the number of patients accrued to clinical trials, and a
comparison of the quality of audited research records with those of affiliated
institutions of the CALGB. The consequences of the program were to measure
changes in patterns of care of breast, prostate, colorectal, and lung cancers
during the study period. These included diagnostic, staging, and treatment
changes that occurred over time. RESULTS: 3.3% of incident cases were
accrued to clinical trials during the study period, more often for breast and
colorectal than for lung and prostate cancers. Reasons that were identified for
low accrual were lack of clinical trials for the majority of cases, including the
elderly. More than 65% of the patients in the outreach population were older than
65, compared with 50% at the cancer center. Patterns of care did change for
breast and prostate cancers, but were similar to national trends.
Medical News Today. (2007). "Researchers identify genetic mutation that may alter
patient's responce to cancer therapies. ." from
http://www.medicalnewstoday.com/medicalnews.php?newsid=76253.
Meehan, K. R., E. M. Areman, S. G. Ericson, C. Matias, R. Seifeldin and K. Schulman
(2000). "Mobilization, collection, and processing of autologous peripheral blood stem
cells: development of a clinical process with associated costs." J Hematother Stem Cell
Res 9(5): 767-71.
We surveyed five academic medical centers to develop a clinical process for
patients undergoing cytokine mobilization and leukapheresis prior to autologous
peripheral blood stem cell transplantation. Costs were obtained from three
centers and applied to each component of the pathway. Costs were divided into
three categories: (1) pre-apheresis evaluation; (2) process of apheresis; (3) postapheresis and peripheral blood stem cells processing. All centers participated in
the development of the leukapheresis pathway. Because charges vary greatly
among institutions, costs were determined from three of the institutions and a
mean was calculated for each of the components of the process. Pre-apheresis
costs consisted of central line placement, blood work, and the price of cytokine
(rhG-CSF). Costs associated with apheresis included professional fees (for
physicians and nurses), leukapheresis with stem cell cryopreservation, storage,
Emerging Issues256
sterility testing, analysis of circulating CD34+ cell counts, and 1 day of cytokine
therapy. The post-apheresis process included thawing with sterility testing along
with CD34+ cell number analysis and the performance of clonogenic assays.
Total costs were as follows: (1) pre-apheresis, $2711; (2) apheresis, $2990; and,
(3) post-apheresis/stem cell processing, $754. This survey from five academic
medical centers provides the average costs associated with three main
components of the apheresis procedure. Because many patients require multiple
aphereses, interventions to achieve target CD34+ cell collections in as few
collections as possible would result in significant cost reduction.
Meehan, K. R., T. Fitzmaurice, L. Root, E. Kimtis, L. Patchett and J. Hill (2006). "The
financial requirements and time commitments of caregivers for autologous stem cell
transplant recipients." J Support Oncol 4(4): 187-90.
This study is a prospective evaluation of the time commitment and financial
requirements of caregivers of autologous stem cell recipients during the period of
inpatient hospitalization. Eligible patients identified one caregiver, and a onepage survey addressing the necessary time commitment and out-of-pocket
expenses was completed by the caregiver at each visit.The caregivers of 40
patients participated (non-Hodgkin's lymphoma [n = 19], multiple myeloma [n =
18], Hodgkin's lymphoma [n = 2], or acute myelogenous leukemia [n = 1]).
Caregivers included spouses (n = 35), partners/friends (n = 2), or family
members (n = 3). Results were summarized for the patient's total length of stay.
Each caregiver traveled a median of 829 miles over 17.8 hours. Out-of-pocket
expenses varied greatly depending on whether a caregiver stayed in local
accommodations (cohort 1; n = 11) or in the patient's hospital room (cohort 2; n =
29).Total expenses (median) for each caregiver in cohort 1 were dollar 849.35,
including accommodations (dollar 560), gasoline (dollar 87.35), and food (dollar
202).Total expenses (median) for each caregiver in cohort 2 were dollar 181.15,
including gasoline (dollar 70) and food (dollar 111.15). Each caregiver in cohort 1
lost a median of 43.5 hours of work compared with 8 hours for each caregiver in
cohort 2.The results from this prospective study demonstrate that there is a
significant financial and time requirement on the part of the caregiver when a
family member or significant other is hospitalized for an autologous stem cell
transplant.
Meehan, K. R., J. M. Hill, L. Patchett, S. M. Webber, J. Wu, P. Ely and Z. M.
Szczepiorkowski (2006). "Implementation of peripheral blood CD34 analyses to initiate
leukapheresis: marked reduction in resource utilization." Transfusion 46(4): 523-9.
BACKGROUND: Analysis of the peripheral blood (PB) C34 value may determine
the optimal time to initiate leukapheresis. STUDY DESIGN AND METHODS:
After selecting a threshold PB CD34 value of five CD34 + cells per microL to
initiate leukapheresis procedure, a prospective analysis of 50 consecutive
patients was initiated to identify the optimal time to initiate leukapheresis and its
impact on costs and resource utilization. Clinical decisions were made to
commence or to postpone leukapheresis with this PB CD34 threshold number.
Based on PB CD34 values for each patient, the number of leukapheresis
Emerging Issues257
procedures, postponed or canceled, the number of CD34+ cells per kg, and the
total number of cells collected were identified. Costs of mobilization were
obtained from the hospital cost accounting system. RESULTS: In 13 months, 50
patients with a hematologic disorder underwent mobilization. There were 34
cancellations or postponements of collections due to a low PB CD34 value in 13
patients. By use of our identified costs per initial collection, this resulted in a
savings of 67,660 US dollars. CONCLUSIONS: This prospective study defines
how the implementation of the PB CD34 value results in costs savings. A low PB
CD34 value canceled or postponed a significant number of leukapheresis
procedures, resulting in a substantial cost savings. Use of the PB CD34 value
should be the standard of care during mobilization and peripheral blood
progenitor cell collection.
Meehan, K. R., R. Slack, E. Gehan, H. B. Herscowitz, E. M. Areman, M. Ebadi, M. S.
Cairo and M. E. Lippman (2002). "Mobilization of peripheral blood stem cells with
paclitaxel and rhG-CSF in high-risk breast cancer patients." J Hematother Stem Cell
Res 11(2): 415-21.
Preclinical studies have demonstrated the rapid and efficient mobilization of
hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the
combination of paclitaxel with recombinant human granulocyte colony-stimulating
factor (rhG-CSF). On the basis of these results, a clinical trial was initiated using
rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer
patients. The mobilized PBSC were evaluated for CD34(+) cell number,
mononuclear cell content, and clonogenic potential. One-hundred and seventeen
breast cancer patients received paclitaxel (300 mg/m(2)) administered as a 24-h
continuous intravenous infusion. Forty-eight hours after completing paclitaxel,
rhG-CSF (5 microg/kg) was initiated and continued until completion of PBSC
collection. Leukapheresis was initiated once the white blood cell count reached
1.0 x 10(9)/L. Each collection was evaluated for the numbers of mononuclear
cells (MNC) and CD34(+) cells. Clonogenic potential was enumerated using
colony-forming units-granulocyte-macrophage (CFU-GM) and burst-forming
units-erythroid (BFU-E). Patients receiving paclitaxel with rhG-CSF mobilized a
large number of mononuclear cells/apheresis (mean, 3.7 x 10(8); range, 3.3-4.1)
and CD34(+) cells/apheresis (mean, 7.2 x 10(6); range, 6.1-8.4). The average
number of leukophereses needed was 1.8 (mean, range 1.6-2.0). Colony growth
was normal with 178.9 x 10(5) and 214.8 x 10(5) colonies counted in CFU-GM
and BFU-E assays, respectively. Patients engrafted platelets and neutrophils on
day 10 following transplantation. In conclusion, PBSC mobilization with paclitaxel
and rhG-CSF results in a large number of mononuclear cells and CD34(+) cells
with normal clonogenic potential. The cells engraft normally following high-dose
chemotherapy and autologous stem cell transplantation in high-risk breast cancer
patients. These results demonstrate that paclitaxel with rhG-CSF is an efficient
mobilizing agent in high-risk breast cancer patients.
Meehan, K. R., J. Wu, E. Bengtson, J. Hill, P. Ely, Z. Szczepiorkowski, M. Kendall and
M. S. Ernstoff (2007). "Early recovery of aggressive cytotoxic cells and improved
Emerging Issues258
immune resurgence with post-transplant immunotherapy for multiple myeloma." Bone
Marrow Transplant 39(11): 695-703.
A phase I/II trial evaluated early administration and dose escalation of interleukin
(IL)-2 with granulocyte macrophage colony stimulating factor (GM-CSF) posttransplant. Following melphalan (200 mg/m(2)) and an autologous transplant, IL2 was initiated (day 0) and continued for 4 weeks. GM-CSF (250 mcg/m(2)/day)
began on day 5. Fifteen of 19 patients completed therapy. No treatment-related
deaths occurred. IL-2 (1 x 10(6) IU/m(2)/day) was not tolerated in two of six
patients due to > or =grade 3 fatigue/diarrhea (n=1) or supraventricular
tachycardia (n=1). The maximum tolerated dose of IL-2 was 6 x 10(5)
IU/m(2)/day; this dose was well tolerated by 11 of 13 patients. Neutrophil and
platelet engraftment occurred on day 13 (median; range 10-17 days) and day 13
(median; range 0-74 days), respectively. When compared to control patients,
there was a marked increase in the number of CD3+ T cells (P=0.005), CD4+ T
cells (P=0.01), CD8+ T cells (P=0.001) and CD4+CD25+Treg cells (P=0.015)
post-transplant. Cytotoxicity directed against myeloma cells was markedly
increased when compared to control patients (P=0.017). This unique trial design
using early administration of IL-2 with GM-CSF during the period of
lymphodepletion, demonstrated a marked increase in the number and function of
early cytotoxic effector T cells, without suppression of engraftment.
Mittal, P, E Corteguerra and KR. Meehan (2001). "Post-transplantation immunotherapy
may improve long-term survival in high risk-breast cancer patients." Proc American
Society of Clinical Oncology 20: 14a.
News-Mecical.net. (2007). "Are we looking at cancer vaccines the wrong way?" from
http://www.news-medical.net/?id=27162.
Although there is no data to support this- patients treated for cancer with
vaccines generally live longer than other patients and they also respond better to
subsequent treatment.
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer Treatment: Targeted Treatments. Nancy Ryan. Lee, NH, New
Hampshire Breast Cancer Coalition.
Breast cancer is not just one disease, it has many forms. As we learn more
about various "types" of breast cancer based on molecular biology and genetics,
the hope is to tailor breast cancer treatment to an individual woman's cancer cell
type. An example of research in this area is a trial supported by the National
Breast Cancer Coalition Fund (NBCCF) called the "TAILORx Trial"
(http://www.cancer.gov/clinicaltrials/digestpage/TAILORx), in which a process
called molecular profiling is studied to help determine which women will truly
benefit from chemotherapy. You can read more about this trial on the NCI web
site listed above. Several sites in New Hampshire are recruiting women into this
trial.
Emerging Issues259
Ryan, Nancy (2007). Personal Communication with Stacy Luke- Emerging Issues in
Breast Cancer: Research and Treatment for Metastatic Disease. Nancy Ryan. Lee, NH,
New Hampshire Breast Cancer Coalition.
Heightened awareness about Stage IV, or metastatic breast cancer, brought
about recently by Mrs. Elizabeth Edwards' announcement that her breast cancer
had spread, reinforces the need for research to learn why some women remain
cancer-free after initial treatment and others go on to develop metastatic disease.
We also need better treatment for Stage IV disease.
Suh, N., W. W. Lamph, A. L. Glasebrook, T. A. Grese, A. D. Palkowitz, C. R. Williams,
R. Risingsong, M. R. Farris, R. A. Heyman and M. B. Sporn (2002). "Prevention and
treatment of experimental breast cancer with the combination of a new selective
estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268." Clin Cancer
Res 8(10): 3270-5.
The selective estrogen receptor modulator arzoxifene and the rexinoid LG
100268 were active not only as single agents for prevention and treatment of
breast cancer in the rat model that uses nitrosomethylurea as the carcinogen but
also showed striking synergy, both preventively and therapeutically, in a series of
six experiments with a total of 465 rats. Mechanistic studies in cell culture
reported here suggest that enhancement of stromal-epithelial interactions may
contribute to this synergy. The possible clinical use of the combination of
arzoxifene and LG 100268 for prevention of breast cancer in women at high risk,
for treatment of women in the adjuvant setting, or for treatment of end-stage
disease should now be considered.
Sundaram, S., A. Sea, S. Feldman, R. Strawbridge, P. J. Hoopes, E. Demidenko, L.
Binderup and D. A. Gewirtz (2003). "The combination of a potent vitamin D3 analog, EB
1089, with ionizing radiation reduces tumor growth and induces apoptosis of MCF-7
breast tumor xenografts in nude mice." Clin Cancer Res 9(6): 2350-6.
PURPOSE: The purpose of this research was to evaluate theinfluence of the
combination of the vitamin D(3) analogue EB 1089 with fractionated radiation on
growth and apoptosis of MCF-7 tumor xenografts in athymic mice.
EXPERIMENTAL DESIGN: Four to six-week-old ovariectomized mice were
injected s.c. with MCF-7 tumor cells suspended in Matrigel. When tumors
reached a size of approximately 150-200 mm(3), animals were exposed to EB
1089 (45 pmols/day) for 8 days, whereas mice that were to be irradiated in the
absence of EB 1089 received solvent (Solutol HS15). After the termination of EB
1089 and solvent administration, tumors were irradiated (3 x 5 Gy) over a period
of 3 days using a 300 KV Pantax Therapax irradiator. Tumor growth was
monitored for 25-30 days after the last dose of irradiation in a double-blind
manner; tumor cellularity was assessed by H&E and trichrome staining, cell
proliferation by Ki-67 staining, and apoptosis by terminal
deoxynucleotidyltransferase-mediated nick end labeling assay. Rates of tumor
regression were assessed using a mixed effects statistical model. RESULTS: A
significantly higher rate of decline in tumor volume (7.5% per day) was observed
in mice exposed to radiation subsequent to EB 1089 compared with animals
Emerging Issues260
treated with radiation alone (5.6% per day). Final tumor volumes in animals
irradiated after EB 1089 were approximately 50% lower than in the group that
received radiation alone. Loss of cellularity, a marked reduction in the fraction of
proliferating cells, and the promotion of apoptosis confirmed that the combination
of EB 1089 with radiation was significantly more effective than radiation alone in
blocking tumor cell growth and promoting tumor cell death. CONCLUSIONS: This
work demonstrates that EB 1089 can improve local tumor control by fractionated
radiation, in part through the promotion of apoptotic cell death.
physorg. (2007). "Discovery about obesity drug helping scientists develop new cancer
treatments." from http://www.physorg.com/news103126045.html.
An obesity drug "orlistat" has been found to kill cancerous cells. These
cancerous cells have high levels of fatty acid synthase which is not present in
normal cells, the drug targets fatty cells containing this synthase.
Vaishampayan, U. N., L. K. Heilbrun, A. F. Shields, J. Lawhorn-Crews, K. Baranowski,
D. Smith and L. E. Flaherty (2007). "Phase II trial of interferon and thalidomide in
metastatic renal cell carcinoma." Invest New Drugs 25(1): 69-75.
OBJECTIVES: To evaluate the toxicity and efficacy of interferon and thalidomide
combination in a phase II clinical trial. PATIENTS AND METHODS: Eligibility
included metastatic renal cancer with a maximum of two prior regimens,
performance status of 0-2 and adequate renal, hepatic and bone marrow
function. RESULTS: Twenty patients were enrolled on this phase II trial. Median
age was 60.5 years (Range: 39-75 years). 17 patients had visceral metastases
(lung/liver/both) and 3 patients had lymph node only metastases. A total of 26
cycles of 4 weeks each were administered; median of 1 cycle and range from 0-9
cycles. The therapy was poorly tolerated with grade 3 adverse events noted in 12
(60%) of the 20 patients. No objective responses were noted. Of the 14 response
evaluable patients, one had an unconfirmed response (38% decrease in size)
and one had prolonged disease stabilization for 10 months. The median time to
progression was 1.0 month and median survival was 2.8 months. Pre and post
therapy PET scans were performed nine weeks apart on one patient. The mean
standardized uptake values (SUV) declined from 1.45 (SUV min-max 0.89-1.76)
to 1.12 (SUV min-max 0.55-1.47), denoting anti vascular effect. The patient did
not have an objective response but had a disease stabilization sustained for 10
months. CONCLUSION: The combination of interferon and thalidomide has
minimal efficacy and considerable toxicity which makes this combination
unworthy of future investigation in metastatic renal cancer.
Wu, A., A. Mazumder, R. L. Martuza, X. Liu, M. Thein, K. R. Meehan and S. D. Rabkin
(2001). "Biological purging of breast cancer cells using an attenuated replicationcompetent herpes simplex virus in human hematopoietic stem cell transplantation."
Cancer Res 61(7): 3009-15.
Autologous hematopoietic stem cell transplantation after myelosuppressive
chemotherapy is used for the treatment of high-risk breast cancer and other solid
tumors. However, contamination of the autologous graft with tumor cells may
Emerging Issues261
adversely affect outcomes. Human hematopoietic bone marrow cells are
resistant to herpes simplex virus type 1 (HSV-1) replication, whereas human
breast cancer cells are sensitive to HSV-1 cytotoxicity. Therefore, we examined
the utility of G207, a safe replication-competent multimutated HSV-1 vector, as a
biological purging agent for breast cancer in the setting of stem cell
transplantation. G207 infection of human bone marrow cells had no effect on the
proportion or clonogenic capacity of CD34+ cells but did enhance the
proliferation of bone marrow cells in culture and the proportion of CD14+ and
CD38+ cells. On the other hand, G207 at a multiplicity of infection of 0.1 was able
to purge bone marrow of contaminating human breast cancer cells. Because
G207 also stimulates the proliferation of human hematopoietic cells, it overcomes
a limitation of other purging methods that result in delayed reconstitution of
hematopoiesis. The efficient infection of human bone marrow cells in the
absence of detected toxicity suggests that HSV vectors may also prove useful for
gene therapy to hematopoietic progenitor cells.
Emerging Issues262
SECTION D: PALLIATION
Emerging Issues263
General
Anast, J. W., G. L. Andriole and R. L. Grubb, 2nd (2007). "Managing the local
complications of locally advanced prostate cancer." Curr Urol Rep 8(3): 211-6.
Complications of locally advanced prostate cancer are often overlooked in the
overall treatment of prostate cancer, can have significant morbidity, and can
provide a challenge for the treating urologist. Despite advances in early detection
and treatment of prostate cancer, as many as 10% of patients present with or
develop symptomatic locally advanced prostate cancer. Prostate cancer locally
invading the urethra can be effectively managed with transurethral resection or
ablation procedures or urethral stenting. Obstruction of one or both ureters is
managed with either ureteral stenting or nephrostomy drainage. Bulky pelvic
recurrence resulting in significant hematuria, rectal involvement, or severe pelvic
pain can be difficult to manage, with some advocating cystoprostatectomy or
pelvic exenteration to provide palliation. Surgical intervention for locally advanced
prostate cancer can provide significant improvement in quality of life and should
not be restricted to patients who have curable disease.
Byock, I., J. S. Twohig, et al. (2006). "Promoting excellence in end-of-life care: a report
on innovative models of palliative care." J Palliat Med 9(1): 137-51.
BACKGROUND: Promoting Excellence in End-of Life Care, a national program
of The Robert Wood Johnson Foundation, funded 22 demonstration projects
representing a wide range of health care settings and patient populations to
develop innovative models for delivering palliative care that addressed
documented deficiencies in the care of patients and families facing the final stage
of life. OBJECTIVE: To determine the practicality (feasibility of development and
operation as well as acceptance by stakeholders) of new models of care and to
determine the impact of the models on access to, quality of and financing for
palliative care. DESIGN: The program cannot report scientifically rigorous
outcomes, but the grant-funded projects used a variety of methods and
measures to assess acceptance of new models and their impact from the
perspectives of various stakeholders, including patients and their families,
clinicians, administrators and payers. While it is not possible to aggregate data
across projects, the data reported to the Promoting Excellence national program
office were used to describe program impact with respect to the practicality of
palliative care service integration into existing clinical care settings (feasibility and
acceptance by stakeholders), the availability and use of palliative care services
(access), quality of care (conformance to patient expectations and accepted
clinical standards) and costs of care. SETTINGS AND SUBJECTS: The 22
projects provided services in urban as well as rural settings, in integrated health
systems, hospitals, outpatient clinics, cancer centers, nursing homes, renal
dialysis clinics, inner city public health and safety net systems and prisons.
Populations served included prison inmates, military veterans, renal dialysis
patients, Native Americans, Native Alaskans, and African American patients,
Emerging Issues264
inner-city medically underserved patients, pediatric patients, and persons with
serious mental illness patients. RESULTS: Hosting or adopting institutions
sustained or expanded twenty of the 22 models, and feedback from all
stakeholders was positive. Project sites developed and utilized new palliative
care services and addressed quality through implementation of new standards
and clinical protocols. Costs of care, where they could be assessed, were
unaffected or decreased for project patients versus historical or concurrent
controls. CONCLUSIONS: The 22 Promoting Excellence in End-of Life Care
projects demonstrated that by individualizing patient and family assessment,
effectively employing existing resources and aligning services with specific
patient and family needs, it is possible to expand access to palliative services
and improve quality of care in ways that are financially feasible and acceptable to
patients, families, clinicians, administrators, and payers.
Cobb, J. l., M. J. Glantz, et al. (2000). "Delirium in Patients with Cancer at the End of
Life." Cancer Practice 8(4): 6.
Delirium is a frequently occurring consequence of advanced cancer and is
characterized by disturbances in arousal, awareness, perception, cognition, and
psychomotor behavior. In their early work, Plum and Posner define delerium as a
"floridly abnormal mental state characterized by disorientation, fear, irritability,
misperception of sensory stimuli, and, often visual hallucinations." Patients may
exhibit loud, suspicious, or agitated behavior, alternating with lucid periods.
Symptoms may be more severe at night, and the sleep-wake cycle may be
disturbed, The manifestations of delirium vary from patient to patient and may
fluctuate over time within individual patients, but delrium is often a harbinger of
death in elderly patients and in patients with cancer.
Fellowes, D, K Barnes and S Wilkinson (2004). "Aromatherapy and massage for
symptom relief in patients with cancer." Cochrane Database Syst Rev. 2(CD002287).
BACKGROUND: Aromatherapy massage is a commonly used complementary
therapy, and is employed in cancer and palliative care largely to improve quality
of life and reduce psychological distress. OBJECTIVES: To investigate whether
aromatherapy and/or massage decreases psychological morbidity, lessens
symptom distress and/or improves the quality of life in patients with a diagnosis
of cancer. SEARCH STRATEGY: We searched CENTRAL (Cochrane Library
Issue 1 2002), MEDLINE (1966 to May week 3 2002), CINAHL (1982 to April
2002), British Nursing Index (1994 to April 2002), EMBASE (1980 to Week 25
2002), AMED (1985 to April 2002), PsycINFO (1887 to April week 4 2002),
SIGLE (1980 to March 2002), CancerLit (1975 to April 2002) and Dissertation
Abstracts International (1861 to March 2002). Reference lists of relevant articles
were searched for additional studies. SELECTION CRITERIA: We sought
randomised controlled trials; controlled before and after studies; and interrupted
time series studies of aromatherapy and/or massage for patients with cancer,
that measured changes in patient-reported levels of physical or psychological
distress or quality of life using reliable and valid tools. DATA COLLECTION AND
ANALYSIS: Two reviewers independently assessed trials for inclusion in the
Emerging Issues265
review, assessed study quality and extracted data. Study authors were contacted
where information was unclear. MAIN RESULTS: The search strategy retrieved
1322 references. Ten reports met the inclusion criteria and these represented
eight RCTs (357 patients). The most consistently found effect of massage or
aromatherapy massage was on anxiety. Four trials (207 patients) measuring
anxiety detected a reduction post intervention, with benefits of 19-32% reported.
Contradictory evidence exists as to any additional benefit on anxiety conferred by
the addition of aromatherapy. The evidence for the impact of
massage/aromatherapy on depression was variable. Of the three trials (120
patients) that assessed depression in cancer patients, only one found any
significant differences in this symptom. Three studies (117 patients) found a
reduction in pain following intervention, and two (71 patients) found a reduction in
nausea. Although several of the trials measured changes in other symptoms
such as fatigue, anger, hostility, communication and digestive problems, none of
these assessments was replicated. REVIEWERS' CONCLUSIONS: Massage
and aromatherapy massage confer short term benefits on psychological
wellbeing, with the effect on anxiety supported by limited evidence. Effects on
physical symptoms may also occur. Evidence is mixed as to whether
aromatherapy enhances the effects of massage. Replication, longer follow up,
and larger trials are need to accrue the necessary evidence.
Himelstein, B. P. (2006). "Palliative care for infants, children, adolescents, and their
families." J Palliat Med 9(1): 163-81.
Jocham, HR, T Dassen, G Widdershoven and R Halfens (2006 Sep). "Quality of life in
palliative care cancer patients: a literature review." J Clin Nurs 15(9): 1188-95.
AMS AND OBJECTIVES: This review of the literature intended to get insight into
the international standards of quality of life assessment in palliative care, the
conceptual and research literature addressing illness related quality of life and an
examination of how nurse researchers define and assess this concept in the
context of terminally ill cancer patients. Clearly stated goals for measuring quality
of life as well as an understanding of the pragmatic and theoretical explanations
for current trends in quality of life measurement are fundamental to this focus.
BACKGROUND: Most clinicians and researchers agree that the primary goal of
palliative care is to optimize the quality of life of patients with advanced incurable
diseases through control of physical symptoms and attention to the patient's
psychological, social and spiritual needs. Palliative care therefore is the
achievement of the best quality of life for patients and their families.
Consequently, the outcomes of care should be measured in terms of the extent
to which this goal is achieved. Quality of life is difficult to define and measure; it is
a multidimensional, dynamic and subjective concept. During the past decade,
multidisciplinary research measuring the impact of cancer and its treatment on
the quality of people's lives escalated rapidly in international literature but not in
the German speaking European countries. This international escalation was
accompanied by a proliferation of measurement strategies and tools. Nursing
shared this interest and began to generate substantive research of the
Emerging Issues266
phenomenon. In the oncology and palliative care nursing societies quality of life
and numerous closely related areas of symptom management rank among the
highest research priorities. METHOD: This paper examines nursing literature
published between 1990 and 2004, retrieved through a computer review of
MEDLINE and Cumulative Index of Nursing and Allied Health Literature. The
review includes reports that systematically describe or measure the quality of life
of people with a terminal cancer in palliative care as a variable of interest. This
article also describes conceptual and operational definitions of quality of life and
explores the implicit and explicit goals of research. RESULTS: Quality of life is a
concept relevant to the discipline of nursing. Nurses, especially oncology and
palliative care nurses, actively contributed to the development of the quality of life
concept through instrument development and population description.
CONCLUSION: Nurses working in German palliative care settings do change the
quality of life of patients they care for, but there are no systematic standards of
assessing these outcomes. RELEVANCE TO CLINICAL PRACTICE: There are
challenges related to measuring quality of life in patient-focused palliative care
and research. Systematic quality of life assessment in all palliative care settings
will establish quality assurance and the further development of this very young
discipline in Germany.
McDonah, D. (2007). Interview with Dr. Don McDonah, Chair of the Palliative
Workgroup, by Jaime Ingalls.
A personal communication between the chair the Palliation Workgroup of the
New Hampshire Comprehensive Cancer Collaboration Dr. Don McDonah of St.
Joseph Hospital in Nashua, NH and Jaime Ingalls of Keene State College
occurred on June 14, 2007 pertaining to Palliative Cancer care. Dr. McDonah
communicated that he believes that cancer palliation is much more then just
hospice care and should include managing the symptoms of the patient as well
as the stress that everyone involved in the care may be experiencing. He also
believes that Palliative care begins at birth and continues throughout life. He
expressed his interest in being a resource to anyone needing further information
on Palliative care in the state of New Hampshire.
Meier, D. E. (2005). "Ten Steps to Growing Palliative Care Referrals." Journal of
Palliative Medicine 8(4): 706-708.
Discusses the steps to growing palliative care referrals. Solicitation of support
from the beginning of palliative care; Selection of a team positioned to generate
referrals; Treatment of the physician as a client.
Podnos, Y. D. and L. D. Wagman (2007). "The surgeon and palliative care." Ann Surg
Oncol 14(4): 1257-63.
The incidence of cancer will continue to rise in the United States as the
population ages. Despite the many advances in cancer prevention, detection,
and treatment of neoplastic diseases, the number of people succumbing to their
cancers will similarly increase. As these patients encounter symptoms toward the
end of life, palliative means, both surgical and nonsurgical, must be employed to
Emerging Issues267
alleviate pain and suffering. This article reviews the definitions of palliative care,
methods for evaluating quality of life and effect of interventions, unique aspects
of surgical palliation, attitudes of surgeons concerning palliative surgery, and
data from palliative surgery studies.
Von Gunten, C. F. (2005). "Innovations in Palliative Care." Journal of Palliative Medicine
8(4): 694-695.
Introduces several articles, which focused on palliative care.
Workman, S. and O. E. Mann (2007). "'No control whatsoever': end-of-life care on a
medical teaching unit from the perspective of family members." QJM 100(7): 433-40.
BACKGROUND: In our institution, about one third of annual deaths occur on the
general medical teaching unit. (MTU) The average patient dies on the MTU from
non-malignant disease after 4 weeks in hospital, and approximately 20% of
available beds on the MTU at any time are occupied by patients who will not
survive to discharge, but quality of end-of-life care on the MTU is not routinely
assessed. AIM: To identify areas for improvement in delivering high quality endof-life care on the medical teaching unit. DESIGN: Qualitative study using semistructured interviews. METHODS: Six months after the death of the patient, next
of kin were sent a letter inviting participation; 75 family members were screened
and 50 invitations were mailed out. Interviews were conducted in the home.
Eliciting narratives and direct questioning about important aspects of end-of-life
care were used. RESULTS: Six next of kin agreed to participate. All patients
were described as seriously and chronically ill. None died of cancer. Deaths were
not described as 'good', and some comments suggested that death was
unexpected and not inevitable. There were few concerns about pain control or
unnecessary suffering. Proactive efforts to provide prognostic information or endof-life care were not described. Survival, not palliation, was of central importance.
Consistent with this priority, satisfaction with care provided in the intensive care
unit was high. Follow-up after death was desired, especially if autopsy results
were available. DISCUSSION: Earlier discussions about treatment failure and
end-of-life care, and the need for palliation, appear to be central to improving the
quality of end-of-life care for patients dying on our medical teaching unit. Our
results are consistent with other studies in this area.
Emerging Issues268
Pharmaceutical Palliation
"Chemotherapy as palliation in advanced colon cancer." (2007). J Support Oncol 5(2):
66.
Ali, A. S. and F. C. Hamdy (2007). "The spectrum of prostate cancer care: from curative
intent to palliation." Curr Urol Rep 8(3): 245-52.
Prostate cancer is one of the most prevalent malignancies affecting men in the
developed world. A spectrum of disease states exists and management is
tailored to individual patients. Increasing public awareness and prostate-specific
antigen testing have led to earlier detection and the possibility of cure but have
increased the risk of overtreatment of indolent disease. Advances in curative
modalities have reduced side effects and offer patients a choice of treatments.
Nonetheless, many need no intervention and may be safely treated with active
monitoring. Choice and timing of therapy for locally advanced and recurrent
disease are variable, with potential benefits of early intervention counterbalanced
by side effects of treatment. Progress has been made in the management of
advanced disease; skeletal-related events have been reduced and survival has
been increased. This review examines the evidence and rationale behind the
treatment options from curative intent to management of locally advanced
disease and palliation of metastatic disease.
Braga, S., A. Miranda, R. Fonseca, J. L. Passos-Coelho, A. Fernandes, J. D. Costa and
A. Moreira (2007). "The aggressiveness of cancer care in the last three months of life: a
retrospective single centre analysis." Psychooncology.
Background: There is concern that terminally ill cancer patients are over treated
with chemotherapy, even when such treatment is unlikely to palliate symptoms.
The study objective was to evaluate the use of chemotherapy in the last three
months of life in a cohort of adult patients with advanced solid tumours.Methods:
All adult patients with solid tumours who died in our hospital in 2003 and received
chemotherapy for advanced cancer, were included. Detailed data concerning
chemotherapy and toxicity, in the last three months of life, were collected from
patients' clinical charts.Results: A total of 319 patients were included. Median
age was 61 years. Median time from diagnosis of metastatic disease to death
was 11 months. The proportion of patients who received chemotherapy in the
last three months of life was 66% (n = 211), in the last month 37% and in the last
two weeks 21%. Among patients who received chemotherapy in the last three
months of life, 50% started a new chemotherapy regimen in this period and 14%
in the last month. There was an increased probability of receiving chemotherapy
in the last three months of life in younger patients and in patients with breast,
ovarian and pancreatic carcinomas.Conclusion: There was a large proportion of
patients who received chemotherapy in the last three months of life, including
initiation of a new regimen within the last 30 days. Thus, further study is needed
to evaluate if such aggressive attitude results in better palliation of symptoms at
the end of life.
Emerging Issues269
Fleisch, M. C., P. Pantke, M. W. Beckmann, H. G. Schnuerch, R. Ackermann, M. O.
Grimm, H. G. Bender and P. Dall (2007). "Predictors for long-term survival after
interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers." J Surg
Oncol 95(6): 476-84.
BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow
predicting long-term survival after pelvic exenteration (PE) for locally advanced or
recurrent gynecologic malignancies. METHODS: All patients undergoing PE at
our institution from 1983 to 2002 were screened. In 203 cases data were
obtainable and analyzed with respect to factors predicting outcome considering
morbidity, mortality, and survival. Follow-up data and data concerning late
complications not documented in our records were obtained by telephone
interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for
locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n =
26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with
rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure
was palliation in the remaining cure. Procedures performed were anterior (n =
91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative
radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1
hr, an average of 5.6 units of packed red blood cells were perioperatively
transfused. Microscopically complete resection was achievable in n = 69 patients.
Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients
were available for follow-up. Five-year overall survival in patients treated with a
curative intent was 21%, 5-year survival in those patients with complete resection
was 32%. Forty-two percent of patients with a complete resection without lymph
node involvement, age 30-50, curative intention, and the absence of a pelvic
sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5year survival rate of over 40% could be achieved for nodal-negative patients
without pelvic sidewall infiltration when treated with curative intent and after
complete resection.
Franchi, F., P. Grassi, D. Ferro, G. Pigliucci, M. De Chicchis, G. Castigliani, C. Pastore
and P. Seminara (2007). "Antiangiogenic metronomic chemotherapy and hyperthermia
in the palliation of advanced cancer." Eur J Cancer Care (Engl) 16(3): 258-62.
Among a large series of cancer patients treated with a combination of
chemotherapy and sessions of hyperthermia, particular attention was given to a
specific group of patients with advanced cancer who refused standard,
aggressive, treatment. In these cases, hyperthermia was associated to low-dose
(metronomic) chemotherapy. No toxicity was reported in any of our patients,
while a marginal benefit in terms of tumour progression was observed. During
therapy, we could detect a coagulative perturbation that deserves careful
discussion. In our opinion, this experience should be matter of debate to
conclude if current response criteria (WHO/UICC and RECIST) in treating cancer
patients are really suitable tools to evaluate new, and non-aggressive anticancer
strategies.
Emerging Issues270
Hackbarth, M., N. Haas, C. Fotopoulou, W. Lichtenegger and J. Sehouli (2007).
"Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life
in women's cancers. Results of a prospective study." Support Care Cancer.
PURPOSE: The study aimed to determine the prevalence of dermatological side
effects and its impact on quality of life in patients receiving systemic
chemotherapy for women's cancers. MATERIALS AND METHODS: A
prospective study was conducted on patients with histologically confirmed
advanced women's cancers who were deemed candidates for adjuvant or
palliative chemotherapy. Patients were systemically examined for skin, hair, and
nail side effects. The impact of those side effects on their quality of life was
assessed using the health-related quality of life score (HRQL). RESULTS:
Between April 2001 and October 2001, 91 patients received 1 to 17 (median 4)
courses of chemotherapy. Malignancies included breast cancer (n = 39, 43%),
ovarian cancer (n = 32, 35%), cervical cancer (n = 12, 13%), endometrial cancer
(n = 5, 6%), fallopian tube cancer (n = 2, 2%), and vaginal cancer (n = 1, 1%).
Chemotherapy agents included taxanes (n = 42, 46%), PEG doxorubicin (n = 17,
7%), other anthracyclines (epirubicin and doxorubicin; n = 6, 19%), topotecan (n
= 13, 14%), and other agents (n = 13, 14%). Overall incidence of skin, nail, and
hair side effects was 86.8% (n = 79). Seventeen patients (18.7%) developed a
palmo-plantar erythrodysesthesia (PPE), and nine of those (53%) were of grade
3 in common toxicity criteria scale (NCI). Twenty-one patients (23.1%) developed
nail changes such as subungual hematomas, onycholysis, and leukonychias or
nail loss, while 69 (75.8%) developed hair loss. There was a higher incidence of
PPE in patients receiving chemotherapy for palliation rather than cure (percent
over percent, p < 0.001, Fisher's exact test). Using the HRQL score, skin
changes were the most frequently reported unpleasant side effect (34.1%), and
of those patients who developed PPE, this was reported by n = 8 (47%) as the
most unpleasant. CONCLUSIONS: Dermatological chemotherapy side effects
are frequent after treatment of women's cancers and have a major impact on
quality of life as assessed by HRQL. Counseling of patients with women's
cancers and the profile of side effects of chemotherapeutic agents should be
considered before considering an adjuvant or palliative chemotherapy regimen.
Haddad, A., M. Davis and R. Lagman (2007). "The pharmacological importance of
cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for
avoiding adverse drug interactions." Support Care Cancer 15(3): 251-7.
BACKGROUND: Adverse drug interactions are major causes of morbidity,
hospitalizations, and mortality. The greatest risk of drug interactions occurs
through in the cytochrome system. CYP3A4, the most prevalent cytochrome,
accounts for 30-50% of drugs metabolized through type I enzymes. MATERIALS
AND METHODS: Palliative patients received medications for symptoms and comorbidities, many of which are substrate, inhibitors, or promoters of CYP3A4
activity and expression. A literature review on CYP3A4 was performed pertinent
to palliative medicine. DISCUSSION: In this state of the art review, we discuss
the CYP3A4 genetics, and kinetics and common medications, which are
Emerging Issues271
substrates or inhibitor/promoters of CYP3A4. CONCLUSION: We made some
recommendations for drug choices to avoid clinically important drug interaction.
Jassem, J. (2007). "The role of radiotherapy in lung cancer: where is the evidence?"
Radiother Oncol 83(2): 203-13.
Radiotherapy is one of the main treatment modalities in lung cancer, contributing
to both its cure and palliation. Thoracic irradiation has traditionally been
considered the mainstay of treatment in inoperable stage III non-small cell lung
cancer. However, despite technical developments and the addition of
chemotherapy, the curative potential of radiotherapy in this subset of patients is
disappointingly poor. The role of radiotherapy as an adjunct to pulmonary
resection (preoperative and postoperative) is questionable, but well-designed
and executed phase III studies are lacking. An important application of
radiotherapy is palliation of tumor-related symptoms in the chest and in
metastatic sites, such as bones and brain. In small cell lung cancer, routine
applications of radiotherapy include chest radiotherapy in limited disease and
prophylactic cranial irradiation in complete responders to chemotherapy, each
increasing survival by about 5%.
Lutz, S. T., E. L. Chow, W. F. Hartsell and A. A. Konski (2007). "A review of
hypofractionated palliative radiotherapy." Cancer 109(8): 1462-70.
Radiotherapy commonly is employed to address symptoms in patients with
symptoms caused by cancer. For this article, the authors reviewed data
supporting the use of hypofractionated palliative radiotherapy. In addition to
single-fraction treatment for painful bony metastasis, the available literature
suggested that courses of 2 to 14 external-beam fractions may provide
equivalent relief to longer course treatment in patients with a poor prognosis who
have primary cancers of the lung, rectum, bladder, prostate, head and neck,
spleen, and gynecologic system. Hypofractionated treatment delivers palliation
that is time efficient, cost effective, and minimally toxic. Evidence suggests that
the reluctance of radiation oncologists to provide single-fraction treatment acts as
a barrier to referrals from palliative care professionals. Collaboration in
education, research, and patient advocacy will advance the common objectives
of the 2 specialties and lead to an appropriate increase in the use of palliative
hypofractionated radiotherapy.
McCloskey, S. A., M. L. Tao, C. M. Rose, A. Fink and A. M. Amadeo (2007). "National
survey of perspectives of palliative radiation therapy: role, barriers, and needs." Cancer
J 13(2): 130-7.
PURPOSE: Despite growth of palliative care programs and evidence on the
effectiveness of radiotherapy in palliating cancer symptoms, radiotherapy is
probably underused in this setting. Radiation and medical oncologists and
palliative medicine specialists were surveyed regarding the perceived role of
palliative radiotherapy and barriers to its use. METHODS: The survey was sent
electronically to all physician members of the American Society for Therapeutic
Radiology and Oncology (ASTRO) and the American Academy of Hospice and
Emerging Issues272
Palliative Medicine (AAHPM) and a random sample of American Society of
Clinical Oncology (ASCO) members, with known e-mail addresses. RESULTS:
Response rates were 27%, 14% and 26% for ASTRO, ASCO, and AAHPM
respondents, respectively. Although most felt radiotherapy is an effective and
important option for palliation of some common cancer symptoms, referrals for
such therapy may be declining. Most agreed that radiation oncologists should be
more involved in palliative care; however, multiple barriers were identified, such
as poor reimbursement, emotional burden of care, insufficient
training/knowledge, and the sense of unwillingness of others to share delivery of
such services. CONCLUSIONS: Although multiple barriers limit optimal
integration, most agree that there should be greater national and professional
society efforts to promote the advancement of radiation oncology in the area of
palliative care.
Rizk, S., A. Robert, A. Vandenhooft, M. Airoldi, G. Kornek and J. P. Machiels (2007).
"Activity of chemotherapy in the palliative treatment of salivary gland tumors: review of
the literature." Eur Arch Otorhinolaryngol 264(6): 587-94.
Chemotherapy is sometimes used as palliation for patients with salivary gland
tumors not amenable to curative treatment. However, if chemotherapy improves
survival is unknown. To identify some prognostic parameters in this disease, we
conducted an extensive review of the literature. The prognostic value of the
baseline clinical characteristics and the different chemotherapy regimens used
was assessed using the Cox proportional hazards regression model on the
available individual data. In addition, the effect of the different chemotherapy
drugs on median survival time was evaluated using meta-weighted linear
regression with dummy covariates referring to each chemotherapy drug. The
total number of patients included in these studies that fit our inclusion criteria was
264 patients. By reviewing carefully the papers and by contacting the different
authors, we were able to retrieve the individual data of 205 patients. In the
multivariate Cox analysis, only the use of platinum-based chemotherapy was
identified as an independent predictor of an increased survival (P = 0.01). These
results were confirmed in a meta-analysis where median survival was increased
by 2.5 (95% IC:0.7-4.4) and 4.9 (95% IC:0.45-9.4) months for patients treated
with platinum (P = 0.007) and anthracyclin-based (P = 0.03) chemotherapy,
respectively. Although exploratory, our analysis suggests that treatment with a
platinum-based chemotherapy regimen may be an independent factor of better
survival for patients with incurable salivary gland neoplasms.
Scartozzi, M., E. Galizia, L. Verdecchia, R. Berardi, S. Antognoli, S. Chiorrini and S.
Cascinu (2007). "Chemotherapy for advanced gastric cancer: across the years for a
standard of care." Expert Opin Pharmacother 8(6): 797-808.
Chemotherapy is of crucial importance in advanced gastric cancer patients, in
order to obtain palliation of symptoms and improve survival. The most
extensively studied drugs as single agents are 5-fluorouracil, cisplatin,
doxorubicin, epirubicin, mitomycin C and etoposide. Newer chemotherapeutic
agents include the taxanes (docetaxel and paclitaxel), oral fluoropyrimidines
Emerging Issues273
(capecitabine and S-1), oxaliplatin and irinotecan. Randomised trials comparing
monotherapy with combination regimens have consistently shown increased
response rates in favour of combination regimens, whereas only marginally
improved survival rates were usually found. Several combination therapies have
been developed and have been examined in Phase III trials. However, in most
cases, they have failed to demonstrate a survival advantage over the reference
arm. There is no internationally accepted standard of care, and uncertainty
remains regarding the choice of the optimal chemotherapy regimen. The
objective of this article is to review the present literature available on major
Phase II - III clinical trials, in which patients suffering from advanced gastric
cancer were treated with cytotoxic chemotherapy.
Simmonds, P. C. (2000). "Palliative chemotherapy for advanced colorectal cancer:
systematic review and meta-analysis. Colorectal Cancer Collaborative Group." Bmj
321(7260): 531-5.
OBJECTIVES: To determine the benefits and harms of palliative chemotherapy
in patients with locally advanced or metastatic colorectal cancer and to compare
the outcomes for elderly and younger patients. DESIGN: Meta-analysis of
individual patient data and published summary statistics from trials for which
individual patient data could not be obtained from the investigators. STUDIES: All
randomised controlled trials comparing palliative chemotherapy with supportive
care in patients with advanced colorectal cancer that were identified by
computerised and hand searches of the literature, scanning references, and
contacting investigators. MAIN OUTCOME MEASURES: Survival, disease
progression, quality of life, and toxicity. RESULTS: 13 randomised controlled
trials including a total of 1365 patients met the inclusion criteria. Meta-analysis of
seven trials that provided individual patient data (866 patients) showed that
palliative chemotherapy was associated with a 35% reduction in the risk of death
(95% confidence interval 24% to 44%). This translates into an absolute
improvement in survival of 16% at both six and 12 months and an improvement
in median survival of 3.7 months. No age related differences were found in the
effectiveness of chemotherapy, but elderly patients were under represented in
trials. The overall quality of evidence relating to treatment toxicity, symptom
control, and quality of life was poor. CONCLUSIONS: Chemotherapy is effective
in prolonging time to disease progression and survival in patients with advanced
colorectal cancer. The survival benefit may be underestimated in this analysis as
some patients in the control arms received chemotherapy.
Stinnett, S., L. Williams and D. H. Johnson (2007). "Role of chemotherapy for palliation
in the lung cancer patient." J Support Oncol 5(1): 19-24.
Lung cancer is the leading cause of cancer-related deaths in the United States
and presents with a constellation of common, often persistent, and severe
symptoms. Chemotherapy is well known to impart a survival benefit; however,
the benefit of chemotherapy for relief of lung cancer symptoms has been slow to
gain recognition. Tumor-related symptoms such as pain, cough, and dyspnea are
improved, along with constitutional symptoms such as fatigue and overall quality
Emerging Issues274
of life, sometimes even after failure of previous regimens. The efficacy of
chemotherapy for the relief of symptoms and improvement in quality of life makes
these drugs a fundamental part of palliative care.
Tey, J., M. F. Back, T. P. Shakespeare, R. K. Mukherjee, J. J. Lu, K. M. Lee, L. C.
Wong, C. N. Leong and M. Zhu (2007). "The role of palliative radiation therapy in
symptomatic locally advanced gastric cancer." Int J Radiat Oncol Biol Phys 67(2): 3858.
PURPOSE: To review the outcome of palliative radiotherapy (RT) alone in
patients with symptomatic locally advanced or recurrent gastric cancer.
METHODS AND MATERIALS: Patients with symptomatic locally advanced or
recurrent gastric cancer who were managed palliatively with RT at The Cancer
Institute, Singapore were retrospectively reviewed. Study end points included
symptom response, median survival, and treatment toxicity (retrospectively
scored using the Common Toxicity Criteria v3.0 [CTC]). RESULTS: Between
November 1999 and December 2004, 33 patients with locally advanced or
recurrent gastric cancer were managed with palliative intent using RT alone.
Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had
known distant metastatic disease at time of treatment. Key index symptoms were
bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The
majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation
regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median
survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of
patients (13/24) with bleeding responded (median duration of response of 140
days), 25% of patients (2/8) with obstruction responded (median duration of
response of 102 days), and 25% of patients (2/8) with pain responded (median
duration of response of 105 days). No obvious dose-response was evident. One
Grade 3 CTC equivalent toxicity was recorded. CONCLUSION: External beam
RT alone is an effective and well tolerated modality in the local palliation of
gastric cancer, with palliation lasting the majority of patients' lives.
Yi, S. K., M. Yoder, K. Zaner and A. E. Hirsch (2007). "Palliative radiation therapy of
symptomatic recurrent bladder cancer." Pain Physician 10(2): 285-90.
BACKGROUND: Palliative radiation therapy (RT) is an established tool in the
management of symptoms caused by malignancies. RT is effective at palliating
both locally advanced and metastatic cancer, including related symptoms of pain,
bleeding, or obstruction. Most data on palliative RT is in regard to its use in the
treatment of painful bone metastases. There are also data that support RT
palliation for locally advanced or recurrent rectal, prostate, and gynecological
cancers. With regard to bladder cancer there is some evidence of the benefit of
palliative RT for the control of urinary symptoms and hematuria; however, there
is little evidence for the use of palliative RT for pain associated with locally
recurrent bladder cancer. We report a case of locally advanced recurrent bladder
cancer which was refractory to medical pain management, and was found to be
highly responsive to palliative RT. CASE REPORT: An 80-year-old woman with
recurrent bladder cancer and intractable pelvic pain refractory to oral and
Emerging Issues275
transdermal pain medications, received palliative pelvic RT to a dose of 50 Gy
(5000 cGy) in 25 fractions with complete resolution of pain. The patient was
originally found to have dysuria, frequency, and hematuria, secondary to an
invasive high grade transitional cell carcinoma of the bladder with an
adenocarcinoma component, AJCC pT2b N1 M0 Stage IV, for which she
underwent a radical cystectomy, total abdominal hysterectomy, bilateral salpingooophorectomy, partial vaginectomy, and ileal conduit reconstruction. After
undergoing 4 cycles of adjuvant chemotherapy, the patient did well for 5 months
with no evidence of symptomatic, clinical, or radiographic recurrence of disease.
Repeat staging CT of the abdomen and pelvis confirmed tumor recurrence in the
left pelvis. The patient was treated with another course of chemotherapy and
pain was managed with relatively low doses of opioid medication (25mcg
transdermal fentanyl patch, and oxycodone 5mg bid). However at the fourth
month, there was rapid escalation of severe pain with the patient becoming bed
bound due to pain with an associated decrease in ambulation and anorexia.
Ultimately a pain medication regimen of 200mcg transdermal fentanyl patch q2
days, oxycontin 20mg bid, oxycodone 5 - 10mg q 4 hours, ibuprofen 400mg q 8
hours, and gabapentin 600mg TID was not effective in controlling pain. The
patient was then referred to Radiation Oncology 6 months after the pain initially
began for evaluation. She received a total of 5000cGy over 25 fractions to a
small pelvis field over 5 weeks and reported complete pain resolution. She was
able to decrease pain medications, increase overall activity, and gain significant
improvement in sleep quality and appetite even early on in the course of her
radiation therapy. CONCLUSIONS: Palliative radiation therapy has been well
studied in the setting of bone metastases and treatment of hematuria for locally
advanced bladder cancer. There is little data that we are aware of on the use of
RT for pain control with patients that have recurrent, locally advanced bladder
cancer. We have presented a case in which an excellent outcome in pain control
was seen for a patient with medically unmanageable pain. RT is an excellent
option for pain management in recurrent bladder cancer and should be offered to
patients whose pain is not otherwise optimally controlled. Palliative RT is an
important component in the multimodality approach to cancer pain management
and optimization of quality of life.
Emerging Issues276
Emotional, Spiritual, and Social Palliation
"Cancer survivors: issues in symptom management." (2007). J Support Oncol 5(2): 73.
A one page article depicting information pertaining to symptom management of
cancer patients that includes the late-effects and quality-of-life issues patients
may experience.
Astin, John A., Shauna L. Shapiro, David M. Eisenberg and Kelly L. Forys (2003).
"Mind-Body Medicine: State of the Science, Implications for Practice." J Am Board Fam
Pract 16(2): 131-147.
Background: Although emerging evidence during the past several decades
suggests that psychosocial factors can directly influence both physiologic
function and health outcomes, medicine had failed to move beyond the
biomedical model, in part because of lack of exposure to the evidence base
supporting the biopsychosocial model. The literature was reviewed to examine
the efficacy of representative psychosocial-mind-body interventions, including
relaxation, (cognitive) behavioral therapies, meditation, imagery, biofeedback,
and hypnosis for several common clinical conditions. Methods: An electronic
search was undertaken of the MEDLINE, PsycLIT, and the Cochrane Library
databases and a manual search of the reference sections of relevant articles for
related clinical trials and reviews of the literature. Studies examining mind-body
interventions for psychological disorders were excluded. Owing to space
limitations, studies examining more body-based therapies, such as yoga and tai
chi chuan, were also not included. Data were extracted from relevant systematic
reviews, meta-analyses, and randomized controlled trials. Results: Drawing
principally from systematic reviews and meta-analyses, there is considerable
evidence of efficacy for several mind-body therapies in the treatment of coronary
artery disease (eg, cardiac rehabilitation), headaches, insomnia, incontinence,
chronic low back pain, disease and treatment-related symptoms of cancer, and
improving postsurgical outcomes. We found moderate evidence of efficacy for
mind-body therapies in the areas of hypertension and arthritis. Additional
research is required to clarify the relative efficacy of different mind-body
therapies, factors (such as specific patient characteristics) that might predict
more or less successful outcomes, and mechanisms of action. Research is also
necessary to examine the cost offsets associated with mind-body therapies.
Conclusions: There is now considerable evidence that an array of mind-body
therapies can be used as effective adjuncts to conventional medical treatment for
a number of common clinical conditions.
Avis, N. E., E. Ip and K. L. Foley (2006). "Evaluation of the Quality of Life in Adult
Cancer Survivors (QLACS) scale for long-term cancer survivors in a sample of breast
cancer survivors." Health Qual Life Outcomes 4: 92.
BACKGROUND: This paper evaluates psychometric properties of a recently
developed measure focusing on the health-related quality of life (HRQL) of longterm cancer survivors, the Quality of Life in Adult Survivors scale (QLACS), in a
Emerging Issues277
sample of breast cancer survivors. This represents an important area of study,
given the large number of breast cancer patients surviving many years post
diagnosis. METHODS: Analyses are based on an 8-year follow-up of a sample of
breast cancer survivors who participated in an earlier study conducted in 1995.
Participants were re-contacted in 2003 and those who were reachable and
agreed to participate (n = 94) were surveyed using a variety of measures
including the QLACS. Additional follow-up surveys were conducted 2 weeks and
one year later. Psychometric tests of the QLACS included test-retest reliability,
concurrent and retrospective validity, and responsiveness. RESULTS: The
QLACS domain and summary scores showed good test-retest reliability (all testretest correlations were above .7) and high internal consistency. The Generic
Summary Score showed convergent validity with other measures designed to
assess generic HRQL. The Cancer-Specific Summary score exhibited divergent
validity with generic HRQL measures, but not a cancer-related specific measure.
The QLACS Cancer-Specific Summary Score demonstrated satisfactory
predictive validity for factors that were previously shown to be correlated with
HRQL. The QLACS generally demonstrated a high level of responsiveness to life
changes. CONCLUSION: The QLACS may serve as a useful measure for
assessing HRQL among long-term breast cancer survivors that are not otherwise
captured by generic measures or those specifically designed for newly diagnosed
patients.
Byock, I. (2007). "To life! Reflections on spirituality, palliative practice, and politics." The
American Journal of Hospice and Palliative Care 23(6): 436-438.
Carey, L. (2005). "Bosom Buddies: a practical model of expressive disclosure." J
Cancer Educ 20(4): 251-5.
BACKGROUND: A writing and theatre workshop, conducted in northern New
Hampshire with 8 posttreatment breast cancer survivors, utilized expressive
disclosure in a nonscientific environment. METHOD: Through writing, the
participants have explored both negative and positive feelings about cancer and
its impact on their lives. Through theatre games and rehearsals, the participants
have had the opportunity to learn new expressive skills. In performance, they
have helped others by telling their own stories. RESULTS: Participants reported
a feeling of transformation and a renewed sense of well-being as a result of the
workshop, as well as an ongoing desire to positively affect others with their work.
CONCLUSIONS: The facilitators and participants agreed that the results of this
work have been transformative for all involved. The facilitators are encouraged
by the idea of further practical exploration of these methods. This article is a
blueprint for this type of work and an exploration of the scientific background that
supports this method as a valid tool to aid in emotional recovery.
Fletcher, K. E., L. Clemow, B. A. Peterson, S. C. Lemon, B. Estabrook and J. G. Zapka
(2006). "A path analysis of factors associated with distress among first-degree female
relatives of women with breast cancer diagnosis." Health Psychol 25(3): 413-24.
Emerging Issues278
Patterns and predictors of psychological distress in first-degree female relatives
(N = 624) of newly diagnosed breast cancer patients were explored. First-degree
female relatives who were high monitors reported greater cancer-specific and
general distress than did low monitors. Greater optimism was associated with
lower cancer-specific distress. Optimism's effect on general distress was
moderated by women's level of monitoring. Greater optimism was associated
with lower general distress for both high and low monitors, but the effect was
stronger for high monitors than for low monitors. Avoidance and engaged coping
were associated with higher distress. A close relationship with the cancer patient
was related to higher cancer-specific distress but lower general distress. Further
understanding of the process of adjustment in these women awaits longitudinal
study.
Redd, William H., Guy H. Montgomery and Katherine N. DuHamel (2001). "Behavioral
Intervention for Cancer Treatment Side Effects." J. Natl. Cancer Inst. 93(11): 810-823.
The use of increasingly aggressive methods of cancer treatment during the last
20 years has brought clinical attention to the need for more effective
management of pain, nausea, and other aversive side effects of state-of-the-art
cancer therapy. One of the most promising approaches to effective management
is nonpharmacologic intervention based on behavioral research and theory. The
purpose of this review is to examine the effectiveness of behavioral intervention
methods in the control of aversive side effects of cancer treatments. Fifty-four
published studies using a variety of research designs were identified for review.
Results indicated the following: 1) Behavioral intervention can effectively control
anticipatory nausea and vomiting in adult and pediatric cancer patients
undergoing chemotherapy; however, the evidence for the efficacy of behavioral
intervention to control post-chemotherapy nausea and vomiting is less clear. 2)
Behavioral intervention integrating several behavioral methods can ameliorate
anxiety and distress associated with invasive medical treatments. 3) Although a
variety of behavioral methods have been shown to reduce acute treatmentrelated pain, there is increasing evidence that these methods are not equally
effective. Hypnotic-like methods, involving relaxation, suggestion, and distracting
imagery, hold the greatest promise for pain management. Unfortunately,
research is scant on the use of behavioral intervention to control prolonged pain
associated with invasive medical procedures. It is clear that the application of
behavioral theory and methods has an important place in the care of patients
undergoing invasive cancer treatments.
Emerging Issues279
Medical Marijuana
Medical marijuana is a key alternative (2007). USA Today: 10a.
Mayo Clinic endocrinologist Victor Montori's comments that his patients must
choose medications on the basis of "the least painful poison," rather than by the
benefit, exposes a plight affecting all patients ("Diabetics face risk on drug
choices," News, June 5).
Many patients often begin exploring the medical uses of cannabis to treat the side
effects of conventional medications. That's why it's so maddening to hear
politicians say things such as, "There are other options," as Rudy Giuliani said
recently when asked about medical cannabis for cancer patients.
Dr. Steve Nissen's comments at the Avandia hearing ("This is about patients; it's not
about politics.") appropriately sum up what medical cannabis opponents refuse to
concede: It's about money. The "poison" is not only painful but profitable, and a
portion goes toward funding the sort of candidates, generally Republicans, who
spout, "There are other options," while generations of patients are denied a safer,
often more effective drug alternative.
Biskupic, Joan (2007). Medical pot rejected: Government can prosecute users, justices
decide. USA Today: 1A.
The U.S. government may prosecute sick people who use marijuana under a
doctor's prescription to ease pain, the Supreme Court ruled Monday. The justices
said a federal ban on the drug trumps laws that protect such patients.
The court's 6-3 decision came in an emotionally charged case that tested "medicalmarijuana" laws in California and nine other states intended to protect patients
who use marijuana for medicinal purposes. The case pitted patients with cancer,
AIDS and other serious illnesses who say marijuana eases their pain against the
U.S. government and its desire to prevent illegal drug trafficking. It also was a
test for a Supreme Court that generally has favored states' rights over federal
authority.
Gorter, R. W., M. Butorac, E. P. Cobian and W. van der Sluis (2005). "Medical use of
cannabis in the Netherlands." Neurology 64(5): 917-9.
The authors investigated the indications for cannabis prescription in the
Netherlands and assessed its efficacy and side effects. A majority (64.1%) of
patients reported a good or excellent effect on their symptoms. Of these patients,
approximately 44% used cannabis for >/=5 months. Indications were neurologic
disorders, pain, musculoskeletal disorders, and cancer anorexia/cachexia.
Inhaled cannabis was perceived as more effective than oral administration.
Reported side effects were generally mild.
Klein, T. W. (2005). "Cannabinoid-based drugs as anti-inflammatory therapeutics." Nat
Rev Immunol 5(5): 400-11.
Emerging Issues280
In the nineteenth century, marijuana was prescribed by physicians for maladies
ranging from eating disorders to rabies. However, as newer, more effective drugs
were discovered and as the potential for abuse of marijuana was recognized, its
use as a therapeutic became restricted, and only recently has its therapeutic
potential been re-evaluated. Recent studies in animal models and in humans
have produced promising results for the treatment of various disorders - such as
obesity, cancer, and spasticity and tremor due to neuropathology - with drugs
based on marijuana-derived cannabinoids. Moreover, as I discuss here, a wealth
of information also indicates that these drugs have immunosuppressive and antiinflammatory properties; therefore, on the basis of this mode of action, the
therapeutic usefulness of these drugs in chronic inflammatory diseases is now
being reassessed.
Manderson, Desmond (1999, Winter). "FORMALISM AND NARRATIVE IN LAW AND
MEDICINE: THE DEBATE OVER MEDICAL MARIJUANA USE." Journal of Drug Issues
29(1): 121-133.
The article reports on the debate over the medical use of marijuana. The use of
marijuana or cannabis as a medicine was permitted by the Californian
Constitution for treatment of glaucoma cases and to resist wasting syndrome. It
is also used as an anti-nausea agent during treatments of cancer and AIDS.
However, the marijuana has to be rescheduled under the Controlled Substances
Act and will not be prohibited in absolute terms and will be capable of medical
prescription. This has caused resistance and hostility and has also promoted
drug reform debates.
Scholten, W. K. (2005). "Medicinal cannabis in oncology practice: still a bridge too far?"
J Clin Oncol 23(30): 7755-6; author reply 7756.
Schwartz, Richard H. and Michael J. Sheridan (Feb1997). "Marijuana to prevent nausea
and vomiting in cancer patients: A survey of clinical oncologists." Southern Medical
Journal 90(2).
Presents information about probable usage patterns and potential adverse
effects of medical marijuana based on the survey on American clinical
oncologists. Percentage of oncologists who prescribed selected antiemetics
between 1992 and 1994; Materials and method used in the study; Results of the
survey conducted; Conclusions.
Seamon, Matthew J., Jennifer A. Fass, Maria Maniscalco-Feichtl and Nada A. AbuShraie (2007). "Medical marijuana and the developing role of the pharmacist." American
Journal of Health-System Pharmacy 64(10): 1037-1044.
Purpose. The pharmacology, therapeutic uses, safety, drug-drug interactions,
and drug-disease interactions of medical marijuana are reviewed, and the legal
issues related to its use and the implications of medical marijuana for the
pharmacist are presented. Summary. Marijuana contains more than 460 active
chemicals and over 60 unique cannabinoids. The legal landscape surrounding
marijuana is surprisingly complex and unsettled. In the United States, 11 states
Emerging Issues281
and several municipalities have legalized medical marijuana. Another state
provides legislation that allows patients to claim a defense of medical necessity.
Nevertheless, patients using medical marijuana may never interact with a
pharmacist. Marijuana is a Schedule I controlled substance and its use is illegal
under federal law. Marijuana has a number of purported therapeutic uses with a
broad range of supporting evidence. There are five general indications for
medical marijuana: (1) severe nausea and vomiting associated with cancer
chemotherapy or other causes, (2) weight loss associated with debilitating
illnesses, including HIV infection and cancer, (3) spasticity secondary to
neurologic diseases, such as multiple sclerosis, (4) pain syndromes, and (5)
other uses, such as for glaucoma. Marijuana is associated with adverse
psychiatric, cardiovascular, respiratory, and immunologic events. Moreover,
marijuana may interact with a number of prescription drugs and concomitant
disease states. Conclusion. Several states have legalized the use of marijuana
for chronic and debilitating medication conditions. Pharmacists need to
understand the complex legal framework surrounding this issue so that they can
protect themselves and better serve their patients. [ABSTRACT FROM
AUTHOR]
Smigel, Kara (1997). "Cancer problems lead list for potential medical marijuana
research studies." Journal of the National Cancer Institute 89(17): 1255.
Highlights the cancer-related areas identified by a group of experts which
probably deserve priority, if more research is to be done on the medical use of
smoked marijuana. Report of a meeting by a group of experts convened by the
National Institutes of Health; Use of marijuana to stop emesis and nausea linked
with cancer chemotherapy and cachexia and appetite stimulation in AIDS or
cancer patients.
Twombly, Renee (2006). "Despite Research, FDA Says Marijuana Has No Benefit."
Journal of the National Cancer Institute 98(13): 888-889.
Abstract:The article reports on the statement of the Food and Drug
Administration (FDA) that marijuana has no benefit despite of research. The
issue of medical marijuana has become a battleground between the federal
government and several states. There have been some research saying that
marijuana has certain benefits but no further research has been pushed through.
Emerging Issues282
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