Download Breast Cancer

PROBLEM SPACE
Breast Cancer: What Are The Risks?
Linda Grisham, Massachusetts Bay Community College
Mark Maloney, Spelman College
Kim Gernert, Emory University
Audience: GenEd Biology students
Inspired by the recent Angelina Jolie
health disclosures.
(CNN) -- Actress Angelina Jolie announced in a New York Times op-ed article on
Tuesday that she underwent a preventive double mastectomy after learning that she
carries a mutation of the BRCA1 gene, which sharply increases her risk of developing
breast cancer and ovarian cancer.
"My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent
risk of ovarian cancer, although the risk is different in the case of each woman," Jolie
wrote. "Once I knew that this was my reality, I decided to be proactive and to minimize
the risk as much I could. I made a decision to have a preventive double mastectomy."
http://www.cnn.com/2013/05/14/showbiz/angelina-jolie-double-mastectomy
Videos.
• Angelina Jolie’s double mastectomy puts
genetic testing in the spotlight. What her
choice reveals about calculating risk, cost and
peace of mind.
http://www.cnn.com/2013/05/14/showbiz/angelina-jolie-double-mastectomy
STORY HIGHLIGHTS
• A blood test can detect if a woman
is "highly susceptible" to breast or
ovarian cancer
• Jolie reveals she carries a gene
that increases her risk for cancer
• Her mother died of ovarian cancer
in 2007
http://www.cnn.com/2013/05/14/showbiz/angelina-jolie-double-mastectomy
Risky Business
My doctors estimated that I had an 87 percent risk of breast
cancer and a 50 percent risk of ovarian cancer, although the risk
is different in the case of each woman," Jolie wrote.
• What does “percent risk” mean?
• What does this mean for you?
• What are your risk factors?
Overview
•
•
•
•
•
About cancer
About mutations
About BRCA1 gene.
Genetic testing
SNPs, GWAS.
Background materials:
www.cancerquest.org
.
.
.
Definitions
• Risk
• Relative risk
• Increased risk, Decreased risk
• Incidence
• Mortality
First we will look at incidence.
DATA
Centers for Disease Control and Prevention
U.S. Cancer Statistics: An Interactive Atlas
United States Cancer Statistics (USCS)
View Data Online
1999–2009 Cancer Incidence and Mortality Data
This Web-based report includes the official
federal statistics on cancer incidence from
registries that have high-quality data and cancer
mortality statistics for each year and 2005–2009
combined. It is produced by the Centers for
Disease Control and Prevention (CDC) and the
National Cancer Institute (NCI), in collaboration
with the North American Association of Central
Cancer Registries (NAACCR).
http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx
DATA
Centers for Disease Control and Prevention
U.S. Cancer Statistics: An Interactive Atlas
Cancer Event: Incidence rate or Death rate.
Site: Female Breast
Race / Ethnicity: Black or White
Period: 1999 or 2009.
U.S. State: Georgia or Maryland
http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx
Examine the map. Collect the data.
You will be collecting two sets of data.
Select two states of interest for comparison.
Collect data using the following
parameters.
Cancer Event: Incidence rate.
Site: Female Breast
Race / Ethnicity: Black
Period: 1999 or 2009.
U.S. State: your state.
Repeat for Race / Ethnicity: White
Type data set into Excel worksheet.
Repeat for Death Rate.
Repeat for second state.
http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx
Breast cancer
Incident
Georgia
rate
year
count
population Rank
out of
White
2009
120.9
4348
3221000
21
50
Black
2009
126.1
1754
1594705
30
38
White
1999
127.4
3662
2756311
7
45
Black
1999
103.2
985
1239075
7
34
Breast cancer
Incident
Massachusetts
rate
count
population Rank
out of
Year
White
2009
132.8
4835
2940746
42
50
Black
2009
107.2
225
254227
6
38
White
1999
147.4
4953
2921658
38
45
Black
1999
96.6
152
216145
3
34
Breast Cancer, Georgia versus Massachusetts
White and Black, Year 1999 versus 2009
160
140
• Incidence Rate
120
100
White
80
Black
60
40
20
0
GA wh 1999 GA wh 2009
MA wh 1999 MA wh 2009
• Death Rate
35
30
25
20
White
15
Black
10
5
0
GA wh 1999 GA wh 2009
MA wh 1999 MA wh 2009
Questions? Questions?
• Is the incidence of breast cancer the same for
each group?
• Has the incidence of breast cancer for your
group increased or decreased between 1999
and 2009?
• Has the death rate changed?
• For each group has the incidence and death
rate changed in the same direction?
• New questions?
Uncertainty is normally an intrinsic feature of some
part of nature ----- it is the same for all observers.
Risk is specific to a person -- it is not the
same for all observers. The possibility of rain
tomorrow is uncertain for everyone; but the risk
of getting wet is specific to me.
Taken from: http://www.solver.com/risk-analysis-tutorial
Risk vs. Benefits?
Risk is determined by two factors:
• How often might a particular hazard arise?
• How much harm is likely to result?
List small risks you take everyday?
What are the benefits?
Are the risks worth the benefits?
Risk analysis is the systematic study
of uncertainties and risks we encounter in
business, engineering, public policy, and many
other areas.
Many, but not all, risks involve choices.
By taking some action, we may deliberately
expose ourselves to risk.
TUTORIAL
http://mathbench.umd.edu/homepage/prob_stat.htm
http://mathbench.umd.edu/homepage/prob_stat.htm
E.Singletary, 2003,
Rating the Risk Factors for Breast Cancer
Carotenoid intakes and risk of breast cancer defined by
estrogen receptor and progesterone receptor status:
a pooled analysis of 18 prospective cohort studies.
Am J Clin Nutr 2012;95(3):713-25. doi:
10.3945/ajcn.111.014415.
http://www.ncbi.nlm.nih.gov/pubmed/22277553
• Entire study has ~1 million participants
• Individual studies range from 6,000
participants to 200,000 participants
Questions? Questions?
• Find one study that has a “tight” calculation of
risk.
• Discuss how risks are calculated
• Explain variance
• Why are there different studies?
• Evaluate.
• Ethics in study.
• What study would you design?
Overview
• Risk assessment
• Beyond the Human
Genome Project:
• Personal Genomes
• Microarray analysis
Background materials:
Singletary, 2003
www.personalgenomes.org/
Dorit, 2007
Microarray animations by Davidson.
Risk Factors
• Factors such as alcohol consumption and obesity appear to have
only a small to moderate effect on breast cancer risk.
•
• Hormone replacement therapy and nulliparity have a larger but
still rather moderate effect on breast cancer incidence.
•
• Age is the most reliable factor associated with increased risk of
breast cancer.
• Besides age, only familial history of cancer (e,g, mother or sibling
having had breast cancer) together with a specific BRCA mutation
correlates with a large-fold increase in risk for breast cancer.
• But only 5-10% of breast cancer cases are familial.
Cancer Subtypes (1)
• A better understanding of heterogeneity within breast
cancer cells themselves is important as there are
subpopulations of breast cancers:
• Breast cancers differ in terms of their specific mutations
within tumor suppressor genes such as BRCA1 (that can no
longer prevent cancer)
and
• oncogenes such as estrogen receptor and the epidermal
growth factor receptor HER2 (that promote cancer cell
abnormal cell division) that lead to malignant cancer
• Increase in personal/individual genomes
could provide further clues to cancer risk:
• Having a larger and more varied group of
individuals whose entire genome is known
and whose cancer incidence can be followed
would better identify gene clusters associated
with cancer risk.
Cancer Subtypes (2)
• A better understanding of heterogeneity within
breast cancer cells themselves is important as
there are subpopulations of breast cancers:
• Breast cancer cells differ in terms of other genes
that are upregulated and downregulated. These
gene expression profiles not only define
subpopulations of breast cancer cells but also
provide clues to optimal therapy for the specific
subtype of cancer. This could improve treatment
and prognosis.
Microarray Analysis
Lab activity
match the cDNAs to the
oligonucleotides in the
wells (Carolina Biologicals)
Dorit, 2007
For confirmation of gene expression: Multiblot
Western Blots for protein expression (Kinexus)
• What factors make breast cancer risk
assessment so difficult?
• Why might this improve in the near future?
• What types of genes are involved in cells
becoming cancerous?
• What types of genes contribute to cancer
pathology?
Bibliography
U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2009 Incidence and
Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for
Disease Control and Prevention and National Cancer Institute; 2013. Available
at: www.cdc.gov/uscs.
Breast Cancer The Angelina Effect: TIME’s New Cover Image Revealed. By Jeffrey Kluger May
15, 2013. http://healthland.time.com/2013/05/15/the-angelina-effect-times-new-cover-imagerevealed/#ixzz2WF6pF41U.
www.cancerquest.org
http://www.solver.com/risk-analysis-tutorial
http://mathbench.umd.edu/homepage/prob_stat.htm
www.personalgenomes.org/
Am J Clin Nutr 2012;95(3):713-25. doi: 10.3945/ajcn.111.014415.
http://www.ncbi.nlm.nih.gov/pubmed/22277553