Download lung cancer mortality

Beneficial Effects of Ionizing Radiation
I. Prevention of Cancer
Sep 18 2007
Charles L Sanders, Visiting Professor
Graphic Assistance by Sukwhun Sohn
Department Nuclear and Quantum Engineering, KAIST
[email protected]
Radiobiology Laboratory
Successive generations of rats exposed continuously at
20 mSv/day to 60Co g-rays had significantly longer
lifespans, more robust reproduction and fewer tumors
than unexposed controls.*
*Brown, S.O., Krise, G.M. and Pace, H.B. (1963) Continuous low-dose radiation
effects on successive litters of the albino rat. Radiat. Res. 19, 270-276.
Sanders, C.L. 1963. Effects of continuous low intensity radiation on the cotton
rat. M.S. Thesis, Biology Department, Texas A & M University, College
Station, Texas
This study was inadvertently replicated in
humans due to the accidental introduction of
60Co in structural steel of apartments in
Taiwan
Residents in Taiwan occupied 1700
apartments for up to 20 years (19832003) built with structural steel
contaminated by 60Co
Cohort
Number of
People
Mean Cumulative Dose in
1983-2003 (mSv)
High
1,100
4000
Medium
900
420
Low
8,000
120
All
10,000
600
Residents in Taiwan occupied 1700
apartments for up to 20 years (19832003) built with structural steel
contaminated by 60Co
Cohort
Number of
People
Mean Cumulative Dose in
1983-2003 (mSv)
High
1,100
4000
Medium
900
420
Low
8,000
120
All
10,000
600
Birth Defects were
7% of expected
(93% protected).
Cancer mortality was
3% of expected
(97% protected)
Chen et al. (13 authors) 2007. Effects of cobalt-60 exposure on health
of Taiwan residents suggest new approach needed in radiation
protection. Dose-Response 5:63-75.
Washington State
Franklin County
Benton County
Columbia River
Hanford
nuclear site
All cancer mortality was less than expected in residents of
counties immediately surrounding the Hanford site* and in
Hanford workers**.
*Boice et al. 2006; **Wilkinson 2000
Epidemiological terms for expressing cancer
risk or benefit:
Relative Risk (RR)
RR – risk after radiation exposure/risk without radiation exposure
Standardized Mortality Ratio (SMR)
SMR – observed/expected for age-specific mortality
For this presentation, RR and SMR are considered equivalent
LNT (Linear-No-Threshold) Hypothesis
(promoted by ICRP and IAEA)
RR (SMR) >1.0 = harm
RR (SMR) <1.0 = benefit
LNT (Linear-No-Threshold) Hypothesis
(promoted by ICRP and IAEA)
RR (SMR) >1.0 = harm
RR (SMR) <1.0 = benefit
This means that you prevent
cancer by being exposed to
ionizing radiation
The LNT is NOT accepted by some radioprotection agencies:
The validity of using the LNT hypothesis to estimate radiation risks is
questionable (UNSCEAR, 1972).
No human data provide support for the LNT hypothesis and some
studies… contradict the LNT hypothesis (NCRP, 1995)…it is important to
note that the rates of cancer in most populations exposed to low-level
radiation … have appeared to be decreased (NCRP, 2001).
The LNT hypothesis should not be used at doses <100 mSv for assessing
carcinogenic risks (French Academy of Sciences and National Academy
of Medicine, 2005).
Typical doses from radiological exams in the United States.
[The majority of Americans, including physicians, believe that these
radiation exposures cause cancer]
Source
Dose, mSv
Mammogram X-ray
0.8
Full-mouth Dental X-ray
0.2
CT Scan, Chest
8
CT Scan, Head
2
CT Scan, Whole Body
10
Radiopharmaceutical Exams
3-7
Intravenous Pyelogram
2.5
Upper/Lower GI
3-7
Gallbladder
4
Angioplasty
9
Barium Studies
2-7
99mTc
Example of the misuse of the LNT hypothesis,
1600
Breast Cancer in TB Patients
Receiving multiple Fluoroscopic
Examinations (NEJM 1989; 321:1285)
1200
6
Breast Cancer Deaths per 10Person-Year
which, unfortunately, is common in the published literature
800
400
0
0.00
0.25
0.50
0.75
1.00
1.25
1.50
1.75
Breast Exposure, Gy
The author says: “The data was most consistent with a linear dose-response relationship…Our
additive model of lifetime risk predicts that exposure to 1 cGy at the age of 40 increases the
number of deaths from breast cancer by 42 per million women”.
Relative Risk of All Cause Mortality in published
epidemiological studies of populations receiving low
LET radiation (Sanders, 2007)
10
Relative Risk
All Data
Harm
1
Benefit
0.1
1
10
100
Dose (mSv)
1000
10000
(Vrijheid et al.
Radiat. Res. 167,
2007)
Nuclear workers
employed in 154
facilities in 15
countries were
examined.
Cohort
Mean Dose,
mSv
SMR, All Cause
Mortality
SMR, All Cancer
Mortality
Australia
6.1
0.55
0.65
Belgium
26.6
0.69
0.62
Canada
19.5
0.62
0.76
Finland
7.9
0.86
0.54
France CEA-COGEMA
3.8
0.59
0.65
France EDF
15.8
0.49
0.62
Hungary
5.1
0.40
0.68
Japan
18.2
0.78
0.87
South Korea
15.5
0.52
1.03
Lithuania
40.7
0.40
0.67
Slovak Republic
18.8
0.53
0.69
Spain
25.5
0.45
0.57
Sweden
17.9
0.80
0.95
Switzerland
62.3
0.77
0.91
UK
20.7
0.78
0.81
US Hanford
23.7
0.74
0.80
US INL
10.0
0.70
0.72
US NPP
27.1
0.41
0.65
US ORNL
15.2
0.72
0.82
MEAN
20.0
0.62
0.74
Proponents of the LNT hypothesis attribute
reductions in mortality in nuclear workers to the socalled Healthy Worker Effect (HWE).
HWE has been attributed to pre-employment
medical screening examinations, better working and
socioeconomic conditions, and annual physicals* for
nuclear facility personnel.
*No reduction in all cancer mortality was found in men who
received annual medical physicals compared to men who did not
(Franks et al. 1996. Health Serv. Res. 31:347-363; Friedman et al. 1986. J. Chronic Dis.
39:453-463).
What is Radiation Hormesis?
Low dose of low LET radiations activates a system of
transient protective processes that includes
antioxidants, high efficiency DNA repair,
immunosurveillance and apoptosis removing genomically
unstable (transformed) cells. The result is a reduced
incidence of many diseases from expected frequencies.
Reactive Oxygen Species (ROS) result from breathing an
oxygen atmosphere
Type
Spontaneous
ROS
2 mSv per
Year
DNA oxidative
adducts/cell/day*
106
1 x 10-3
DNA Damage per cell per
year**
70 x 106
4
Double-stranded DNA
breaks per cell per year***
40
~0.1
*Pollycove, M. Radiation Hormesis: The Biological Response to Low Doses of Ionizing Radiation. Health
Effects of Low-Level Radiation, BNES, 2002.
**Billen, D. Spontaneous DNA damage and its significance for the “negligible dose” controversy in
radiation protection. Radiat. Res. 124:242-245, 1990.
***Stewart, R.D. On the complexity of the DNA damages created by endogenous processes. Radiat.
Res. 152:101-105, 1999.
High Dose
Radiation/Chemical-Induced
or ROS-Induced Genomic
Instability
Prevention of radical
damage: Increasing
Antioxidants
Repair of damage:
Increasing DNA repair
Removal of damage:
Apoptosis and
Immunosurveillance
Low Dose, Low DoseRate, Low LET Radiation
DNA Damage
Accumulation
DNA Repair
Neoplastic
Transformation
Apoptosis
Adaptive Response
Proliferation of
Malignant Cells
Cancer
Immune Functions
Hundreds of studies have documented hormesis
response mechanisms.
Dose-dependence for neoplastic transformation of human hybrid
cells exposed to X- and g-rays (Redpath JL, Q Lu, X Lao et al. 2003. Int J Radiat Biol
79:235-240).
15 Gy at 1.2 mGy/h
Lifespan in mice carrying a deletion in the apoptosis-regulating Fas gene
that received chronic g radiation: (a) nonirradiated controls; (b) irradiated
with 0.35 mGy/h for 5 weeks; © irradiated with 0.35 mGy/h for lifespan;
(d) irradiated with 1.2 mGy/h for 5 weeks; (e) irradiated with 1.2 mGy/h
for 521 days (* P<0.0001 from unirradiated controls) (Ina Y and K Sakai. 2005.
Radiat Res 163:418-423).
Hormesis in experimental animal studies
Hormesis is ubiquitous, being found for toxic chemicals and ionizing
radiation (Calabrese. 2006.Toxicol Sci 94:368; Calabrese et al. 2003. Annu Rev Pharmacol
Toxicol 43:175)
Decreased
tumors
Decreased
tumors
MC = Methylcholanthrene (high dose)
Kazuo Sakai, CRIEPI
100
Crude Incidence Lung Tumors, %
169Yb
 175 keV g
169
YbO3 -
239
PuO2
80
60
239Pu
 5.14 meV a
239
PuO2
40
20
0
1E-3
0.01
0.1
1
10
100
Lung Dose, Gy
Frequency of lung tumors in female Wistar rats following
inhalation of 239PuO2 or 169YbO3-239PuO2 (Sanders et al. Radiat. Res.
1976; 68:349; Sanders et al. Intern. J. Radiat. Biol. 1993; 64:417).
Lung cancer in Mayak
plutonium workers
Workers also
accumulated a
mean of 1 Gy
external
60Co g-rays
Relative Risk of Lung Cancer
3
2
Mean239Pu Body
Burden, kBq
RR, Lung
0.010
1.0
0.34
0.56
1.18
0.59
4.2
0.83
16.5
2.48
54.2
59.3
Cancer
1
800 mGy a
Threshold
0
(Tokarskaya et al.
1997 Health Phys.
73:899-905)
0
2
4
239
Pu Body Burden, kBq
6
Possible Explanation
Alpha particles from 239Pu, along with
cigarette smoke, produce genomically
damaged, transformed cells.
Gamma rays from 60Co induce apoptosis of
transformed cells.
Presence of radiation dose thresholds
Approximate Human Threshold Dose-Rate for Low
LET, Near Continuous Radiation Exposure
(KeirimMarkus, 2002. Atomic Energy 93:836;
Parsons, 2003. Biogerontology 4:227)
All Cancer
200 mGy y-1
Bone Tumors in Radium Dial Painters
10 Gy
Threshold
This study was terminated by DOE when it was
found that the radium dial painters were living
longer than the controls.
Participants in the United States Transuranium and
Uranium Registries (USTUR) significantly exceeded ‘life
table’ longevity expectation by an average of 10.4 years.
N. Fallahian, R Brey, C Watson and A James. 2007. Does exposure to plutonium
affect workers’ longevity? Health Physics 93:S11.
Liver cancer in Mayak
plutonium workers
Dose Range, Gy
OR
95% CI
0-0.07
1.0
-
0.07-0.54
0.40
0.14-1.12
0.54-16.9
2.44
1.09-5.44
Threshold for liver tumors was 2.0 Gy
a-dose; no increased liver tumors
from 1.0 Gy external g-rays.
(Tokarskaya et al. 2006. Health Phys. 91:296-310)
Threshold for liver tumors from Thorotrast
(232ThO2) was also 2 Gy. (Van Kaick et al. 1991. J
Radiat Res 32:20-33)
Relative Risk of liver cancer mortality in
published epidemiological studies of
populations receiving low LET radiation
(Sanders, 2007)
10
Relative Risk
All Data
1
0.1
1
10
100
Dose (mSv)
1000
10000
Cumulative WLM
Odds
Ratio*
<50
1.00
50-<100
1.23
100-<200
0.91
200-<400
0.94
400-<800
0.99
800-<1,600
2.08
1,600-2,911
3.68
*adjusted for age, smoking, asbestos
exposure (Health Phys. 2006: 90:208)
German Uranium and Chinese Tin Miners
Relative Risk Lung Cancer
Lung Cancer in German Uranium
Miners
100
1 WLM = 5 mSv
10
1
0.1
1
10
100
1000
10000
100000
Dose, mSv
Uranium Mine Location
Threshold, mSv
Yunnan, China
1000
Colorado Plateau, US
3000
Newfoundland, Canada
2000
Malmberget, Sweden
250
Grants, New Mexico, US
1000
Eastern Germany
4000
Radiation hormesis in populations that are not nuclear
workers (radiation accidents, high natural background,
A-bomb survivors, diagnostic and clinically exposed
medical patients and other groups)
1955
Free Enterprise Radon Health Mine, Montana; air in the
mine reaches 1600 pCi/L; EPA action level is 4 pCi/L
Low dose radiotherapy is an effective therapy for acute and chronic
inflammatory diseases and painful degenerative disorders (O. Micke and M.H.
Seegenschmiedt. 2002. Consensus guidelines for radiation therapy of benign diseases: a
multicenter approach in Germany. Int J Radiat Oncol Biol Phys 52:496-513).
No evidence of increased cancer has been shown in 100,000s of patients that
are annually treated by radon in former uranium mines or spas (balneology).
No study has shown an increased
cancer rate in high radiation
background areas of the world
Location
Background
Dose,
mSv/year
Ramsar, Iran
Up to 700
Kerala, India
Up to 35
Araxa, Brazil
Up to 25
World Average
2.4
Highest radon level,
lowest lung cancer
mortality
Eight health
districts of
Ramsar, Iran
Lowest radon
level, highest lung
cancer mortality
(Mortazavi et al. 2005.
Intern Cong Ser 1276:436)
Source of radiation dose in
Kerala, India
Dose Contribution
Fraction (%)
External g
76
Inhalation a
24
Cumulative
Dose, mSv
RR, All Solid
Cancers
0-99
1.0
100-199
0.83
200-299
0.98
300-399
0.90
>400
0.66
Cancer in Cities of India
(Health Phys 1987; 52:653)
SIR
100
5
(J Radiat Res 2000; 41: Suppl 43)
150
Rate Per 10 Population
Cancer in Yangjiang, China;
background dose-rate is
~6 mSv/y-1
Site of Cancer
ERR per
SV
Liver
-0.99
Stomach
-0.27
Lung
-0.68
SMR
50
0
300
400
500
600
700
800
900
-6
1000
-1
External Natural Background Radiation, (*10 Sv y )
(Taken from Scott. LRRI, 2006)
Corrected for Smoking
Ecological study of radon exposure and
risk of lung cancer; data from 1600
counties in the U.S. (Cohen, 1995; Health Phys.
68:157-174)
Cancer
Sex
Cancers per
100,000 PY
Lung
M
-8.7 ± 0.4
Lung
F
-9.3 ± 0.5
Oral
M
-10.2 ± 0.7
Oral
F
-11.3 ± 0.9
Larynx
M
-8.5 ± 0.8
Larynx
F
-14.1 ± 1.3
Esophagus
M
-4.1 ± 0.7
Esophagus
F
-7.9 ± 1.1
The estimated percentage change in mortality per unit radon
for anatomical sites of smoking related cancer mortality
(Puskin JS. 2003. Health Phys 84:526-532).
Unexposed
Japanese A-bomb survivors live
longer!
Threshold at ~200 mSv, for
solid cancer mortality and
leukemia
(Pierce et al. Rad Res 2000. 154:178;
Mine et al. 1990. Int J Rad Biol 58:1035)
Nagasaki
A-bomb survivors
Unexposed
Japanese A-bomb survivors live
longer!
Nagasaki
A-bomb survivors
Threshold at ~200 mSv, for
solid cancer mortality and
leukemia
(Pierce et al. Rad Res 2000. 154:178;
Mine et al. 1990. Int J Rad Biol 58:1035)
Leukemia
50% less
than
expected
Mean Individual Cumulative SMR, All Cancer Mortality
Dose, mSv
120
0.61*
496
0.72*
SMR for cancer in 10,000s of Eastern Urals residents exposed to radiation
from a nuclear waste tank explosion in 1957
(*significantly less at p <0.05)
Population
Number
of People
Mean Dose
(mSv)
Liquidators
240,000
100
Evacuees
116,000
33
Low Contaminated
Areas
5,200,000
10
High Contaminated
Areas
270,000
50
1986 Chernobyl Fallout Populations
Population
Number
of People
Mean Dose
(mSv)
Liquidators
240,000
100
Evacuees
116,000
33
Low Contaminated
Areas
5,200,000
10
High Contaminated
Areas
270,000
50
1986 Chernobyl Fallout Populations
Initially, using the LNT hypothesis,
53,400 excess cancer deaths were
predicted over first 50 years.
UN Chernobyl Forum (2006) found
no increased cancer mortality.
Dr. Peter Fong
predicted in 1996
that >1,000,000
cancer deaths
might be
prevented.
He may be right!
Cancer deaths have been 15-30% less than expected!
1.1
1.0
SMR
0.9
0.8
0.7
0.6
0.5
90
91
92
93
94
95
96
97
98
99
Calendar Year
SMR for malignant neoplasms among Chernobyl liquidators
(redrawn from Health Physics 2001:81:514-521).
Congenital
Malformations
Low radiation
High radiation
There were an estimated 100,000 excess abortions that resulted from fear
of teratogenic effects following the Chernobyl accident. In fact, women who
received high radiation doses experienced less birth defects (WHO, 2006).
Odds Ratio for cancer in
children whose fathers had
been exposed to ionizing
radiation prior to
conception.
Sever. Final Report
U50/CCU012545-01,
Battelle, Seattle, WA.
1997
Odds Ratio
Dose, mSv
CNS
All Cancers
<1
1.00
1.00
1-50
0.43
0.54
50-100
0
0.95
>100
0
0
Were ‘defective’ spermatogonia
removed by apoptosis?
twins/singletons
Study
California
(Inskip et al. 1991)
Connecticut
Norway
(Inskip et al. 1991)
(Windham et al. 1985)
Sweden
(Rodvall et al. 1992)
Total
No. Twins
Cancer Obs
Cancer Exp
RR
145,708
100
111
0.90
30,925
31
46
0.67
14, 504
14
16
0.90
35,582
59
62
0.95
226,719
204
234
0.87
Twin cohorts have a lower risk of childhood cancer than
singletons despite more frequent X-rays.
Hormesis in populations with internal controls
Compared to
all other UK
physicians
British Radiologists
Years Joined
British Radiological
Societies
Tolerance or
Exposure Limits,
mSv year-1
SMR
All Cancers
Lung Cancer
1897-1920
> 1000
1.75
2.46
1921-1935
700
1.24
1.06
1936-1954
70-350
1.12
0.74
1955-1979
<50
0.71
0
100
80
SMR, %
60
40
1946-79
20
Unexposed
workers
received the
same medical
care
1980-97
Mean Cumulative Dose
43 mSv
11 mSv
0
1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000
Calendar Year
All cause mortality of employees of the United Kingdom Atomic
Energy Authority, 1946–97. Radiation workers compared to
non-radiation workers (redrawn from Occupational and
Environmental Medicine 2004;61:577-585).
Unexposed workers
received the same
medical care
SMR (exposed/unexposed)
Cause of Death
INEEL1 12 US DOE Labs2 Shipyard3
Diseases-Blood & Blood-forming Organs
0.60
0.58
-
Diseases-Respiratory System
0.72
0.86
0.56
Diseases-Digestive System
0.65
0.90
0.71
Diseases-Genitourinary System
0.70
0.65
0.36
Disease-Brain & Nervous System
0.94
0.71
0.51
Leukemia
0.89
0.92
0.93
All Tumors
0.90
0.92
0.85
All Causes
0.82
0.88
0.75
1NIOSH,2005-mean
dose 13 mSv; 2NIOSH, 2000- mean dose 5.8 mSv;
3Int J Low Radiat 2005; 1:463- mean dose 97 mSv
Unexposed workers
received the same
medical care
SMR for causes of death among U.S. shipyard workers. Cumulative doses
in radiation workers ranged from 5-400 mSv (Matanoski 2001).
Use of small hormetic doses to treat cancer
Pulmonary Metastases
Total body irradiation (TBI) of mice given 12 days after tumor cell
transplantation. Lung colonies counted at 20 days after TBI.
(Sakamoto et al. 1997; J Jpn Soc Ther Radiol Oncol 9:161).
Two clinical trials of low dose radiation therapy in patients with
non-Hodgkin’s lymphoma have been published. Patients received
multi-agent chemotherapy alone or added total body irradiation
(TBI) or half-body irradiation (HBI). Both were effective.
Radiation treatment fields of patients with non-Hodgkin’s lymphoma
(Pollycove, 2004).
100mSv 3X/wk X 5wks = 1500 mSv
150mSv 2X/wk X 5wks = 1500 mSv
Use of TBI or HBI non-Hodgkin’s lymphoma (Choi et al. 1979. Cancer 43:16361642).
Comparison of TBI and HBI with chemotherapy and high-dose localized
radiotherapy in non-Hodgkin’s lymphoma (Sakamoto et al. 1997. J Jpn Soc Ther
Radiol Oncol 16:161-175). Some tumors outside the HBI field regressed
completely.
N = 23
N = 94
Implications of Radiation Hormesis are
extremely important
Current radiation protection standards do not protect against cancer;
cancer results from radiation deficiency.
Implications of Radiation Hormesis are
extremely important
Current radiation protection standards do not protect against cancer;
cancer results from radiation deficiency.
Radiation phobia leads to needless fear, abortions, and avoidance of
medical diagnostic procedures.
Implications of Radiation Hormesis are
extremely important
Current radiation protection standards do not protect against cancer;
cancer results from radiation deficiency.
Radiation phobia leads to needless fear, abortions, and avoidance of
medical diagnostic procedures.
Applying hormetic doses of low LET radiation for cancer therapy can
extend and save many lives.
Implications of Radiation Hormesis are
extremely important
Current radiation protection standards do not protect against cancer;
cancer results from radiation deficiency.
Radiation phobia leads to needless fear, abortions, and avoidance of
medical diagnostic procedures.
Applying hormetic doses of low LET radiation for cancer therapy can
extend and save many lives.
Public recognition of hormesis could save tens of billions of dollars
spent in needless radiation protection and clean-up.
Implications of Radiation Hormesis are
extremely important
Current radiation protection standards do not protect against cancer;
cancer results from radiation deficiency.
Radiation phobia leads to needless fear, abortions, and avoidance of
medical diagnostic procedures.
Applying hormetic doses of low LET radiation for cancer therapy can
extend and save many lives.
Public recognition of hormesis could save tens of billions of dollars
spent in needless radiation protection and clean-up.
The public would accept nuclear power facilities, including radioactive
waste disposal sites, if they understood the beneficial effects of low
LET ionizing radiation.
Bias against Radiation Hormesis by Regulatory
Agencies
1.
All radiation is considered harmful without proof.
2. Individuals receiving low doses are included in the unexposed group.
3. Low-dose data are ignored or excluded by expressing as only ERR.
4. Low-dose data are aggregated with higher dose bins to hide evidence
of hormesis.
5. Nonlinearity is not acknowledged.
6. Ecological data showing hormesis is discounted, while ecological data
showing excess cancer is included.
7. Protective mechanisms (DNA repair/apoptosis) are ignored.
8. Evidence of lifespan lengthening are ignored.
9. Hormesis is attributed to the ‘Healthy Worker Effect’.
10. Years of dose accumulation are removed by dose lagging, removing
threshold-like dose responses.
Observations about many radioepidemiological
studies
1. Ecological studies are bad if the result is not what you want, but are
good if the result is what you expect.
2. Using ERR/Dose estimates derived from the LNT hypothesis, while
not publishing data for individual dose points, hides beneficial effects
of radiation at low doses
3. Combining low dose groups with higher dose groups hides beneficial
effects of radiation at low doses
4. Claiming an increased risk of cancer whenever possible, but hesitant
to admit a risk estimate that is less than expected
5. Using the healthy worker effect mantra in spite of the evidence
6. Inadequate determination of confounding biases (eg., smoking)
7. Ignoring papers and data that show hormesis
8. Redo the study to disprove hormesis
9. Denying publication because the data shows hormesis
Bias in Epidemiological Studies
(Ioannidis.2005. Why Most Research Findings Are False. PLOS Medicine 2:8)
1.
Finding is less likely to be true when the effect size is small
2. A research finding is less likely to be true when more teams are
involved in a scientific field in chase of statistical significance.
3. Selective bias entails manipulation in the analysis and reporting of
findings.
4. If the effect size is very small in a scientific field, this field is likely
to be plagued by ubiquitous false positive claims.
5. Prestigious investigators may suppress via the peer review process the
appearance and dissemination of findings that refute their findings.
6. A meta-analysis finding from inconclusive studies where pooling is used
to “correct” the low power of single studies, is probably false.
7. Investigators working in a field are likely to resist accepting that the
whole field in which they have spent their careers is a “null field”.
Relative Risk (RR) – observed/expected
If RR >1, then there is an increased risk from expected
If RR <1, then there is a decreased risk from expected
Standardized Mortality Ratio (SMR) – observed/expected age-specific
mortality
For low doses and dose-rates in the hormetic zone, the Relative Risk (RR)
at dose D is:
RR = 1, for D = 0
RR = 1-PROFACE for D >0
PROFAC = 1-RR (or 1-SMR)
The Protection Factor (PROFAC) gives the proportion of cancer mortality
cases for low LET radiations.
100 x PROFAC = % of spontaneously expected cancers avoided, or
cancers that would have occurred in the absence of radiation hormesis
Each increment of 0.1 PROFAC would be expected to save 10,000 lives
out of a population of 100,000
Factors influencing disease-related mortality in the U.S. (Murray et al. 2006.
PloS Med 3(9).
Epidemiological studies examining the relationship
between radiation exposure and lung cancer include:
(1) case-control studies (indoor radon), where exposure is
compared in individuals with and without lung cancer
(2) ecological studies (environmental radon) that compare average
exposure with average lung cancer risk
(3) cohort studies (uranium miners) that follow cohorts of
underground miners during their lifetime, relating cumulative
exposure with lung cancer rate.
Case-control studies show null effect, while ecologic studies tend
to show benefits from low exposures to radon. Shapes of doseresponse curves derived from epidemiological data should be
treated very cautiously (Crump, 2006).
Ubiquitous false positive claims are more likely in
epidemiological studies when the increased risk is
<100%. The results are difficult to interpret due to
chance, statistical bias and effects of confounding
factors.
Some journals, such as the New England Journal of
Medicine, do not accept epidemiological studies for
publication unless the RR values are <0.5 or >3.0
(Taubes, 1995).
Meta-analysis findings, with pooling of low power single
studies, often prove to be false. These problems are
most often seen in biomedical research (Ioannidis et al.,
2001, Ioannidis, 2005, Vandenbroucke, 2004).
Low dose ionizing radiations:
Enhance removal of reactive oxygen species
Induce repair of DNA damage
Protect from chromosomal damage
Protect from spontaneous DNA mutations
Protect from spontaneous neoplastic transformation
Enhance apoptosis
Protect from spontaneous tumors in animals and humans
Suppress experimental tumors and metastasis in animals
Extend tumor latency in animals
Activate the immune response
Enhance traditional cancer therapy for lymphoma
Protect from many other diseases in humans
Relative Risk of All Cancer Mortality in unabridged published
epidemiological studies of populations receiving low LET radiation
(Sanders, 2007)
10
All Cancer
Relative Risk
(All Data)
1
0.1
1
10
100
Dose (mSv)
1000
Relative Risk of leukemia mortality in
86 published epidemiological studies of
populations receiving low LET radiation
10
Relative Risk
Nuclear Workers
10
1
All Data
0.1
10
100
1000
100
1000
Dose (mSv)
1
10
Others
0.1
1
10
100
Dose (mSv)
1000
10000
Relative Risk
Relative Risk
1
1
0.1
1
10
Dose (mSv)
Relative Risk of breast cancer mortality in
unabridged published epidemiological studies of
populations receiving low LET radiation
(Sanders, 2007)
10
Breast Cancer
Relative Risk
(All Data)
1
0.1
1
10
100
Dose (mSv)
1000
Relative Risk of lung cancer mortality
in 52 published epidemiological studies of
populations receiving low LET radiation
All Data
1
0.1
1
1
10
100
1000
100
1000
Dose (mSv)
10
Others
0.1
1
10
100
Dose (mSv)
1000
10000
Relative Risk
Relative Risk
Nuclear Workers
Relative Risk
10
10
1
0.1
1
10
Dose (mSv)
LNT hypothesis was mainly derived from the leukemia
deaths at high doses of acute radiation: 905 leukemias
observed among 86,572 Hiroshima survivors (1%) :
- with dose >1 Sv, leukemia mortality increased 5 times.
- with dose >2 Sv, leukemia mortality increased 14 times;
represents a cohort of 2,819 survivors (3.2% of total
86,572).
A cohort of 32,915 (44.5% of total 86,572 survivors)
who received a dose of 5-100 mSv, had a decrease in
leukemia mortality.