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PROBLEM SPACE Breast Cancer: What Are The Risks?

PROBLEM SPACE Breast Cancer: What Are The Risks?. Audience : GenEd Biology students. Linda Grisham, Massachusetts Bay Community College Mark Maloney, Spelman College Kim Gernert , Emory University. Inspired by the recent Angelina Jolie health disclosures.

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PROBLEM SPACE Breast Cancer: What Are The Risks?

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  1. PROBLEM SPACE Breast Cancer: What Are The Risks? Audience: GenEd Biology students Linda Grisham, Massachusetts Bay Community College Mark Maloney, Spelman College Kim Gernert, Emory University

  2. 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.

  3. 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

  4. 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

  5. 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?

  6. Overview • About cancer • About mutations • About BRCA1 gene. • Genetic testing • SNPs, GWAS. Background materials: www.cancerquest.org . . .

  7. Definitions • Risk • Relative risk • Increased risk, Decreased risk • Incidence • Mortality First we will look at incidence.

  8. 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 DataThis 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

  9. 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

  10. 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 Repeat for Death Rate. Repeat for second state. Type data set into Excel worksheet. http://apps.nccd.cdc.gov/DCPC_INCA/DCPC_INCA.aspx

  11. Breast Cancer, Georgia versus Massachusetts White and Black, Year 1999 versus2009 • Incidence Rate • Death Rate

  12. 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?

  13. Uncertainty is normally an intrinsic feature of some part of nature ----- it is the samefor all observers.  Risk is specific to a person -- it is not the samefor 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

  14. 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?

  15. 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.

  16. TUTORIAL http://mathbench.umd.edu/homepage/prob_stat.htm

  17. http://mathbench.umd.edu/homepage/prob_stat.htm

  18. E.Singletary, 2003, Rating the Risk Factors for Breast Cancer

  19. 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 ClinNutr 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 from6,000 participants to 200,000 participants

  20. 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?

  21. 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.

  22. 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.

  23. 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

  24. 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.

  25. 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.

  26. Microarray Analysis

  27. Lab activitymatch the cDNAs to the oligonucleotides in the wells (Carolina Biologicals)

  28. Dorit, 2007

  29. For confirmation of gene expression: Multiblot Western Blots for protein expression (Kinexus)

  30. 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?

  31. 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. ByJeffrey Kluger May 15, 2013. http://healthland.time.com/2013/05/15/the-angelina-effect-times-new-cover-image-revealed/#ixzz2WF6pF41U. www.cancerquest.org http://www.solver.com/risk-analysis-tutorial http://mathbench.umd.edu/homepage/prob_stat.htm www.personalgenomes.org/ Am J ClinNutr 2012;95(3):713-25. doi: 10.3945/ajcn.111.014415. http://www.ncbi.nlm.nih.gov/pubmed/22277553

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