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Prostate Genetics 1 December Talk CCSN.pptx
About this Webinar: In 2016 a landmark study put prostate cancer genetics on the map. Year after year there have been more advances in our understanding of prostate cancer to a point now where there’s a lot of information out there. This talk is meant to distill the most practical parts of the prostate cancer genetics story on how this applies to people who have a prostate cancer story, or who are at risk of prostate cancer. This talk will cover the basics of genetics, how to access genetic testing, and how results of genetic testing can impact care. About this presenter: Justin Lorentz is a Certified Genetic Counsellor. He received his Master’s in Genetic Counselling at McGill University in 2012. Justin is based out of Toronto, he practices clinically at Medcan and he leads a registry for men with hereditary cancer at the Sunnybrook Odette Cancer Centre. His academic interests are in hereditary cancer with a focus on prostate cancer genetics.
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Prostate Genetics 1 December Talk CCSN.pptx
- 1. Prostate Cancer Genetics JustinLorentz, MSc, CGC Genetic Counsellor Male Oncology Research and Education (MORE) Lead Sunnybrook Odette Cancer Centre Medcan
- 2. Goals SECTION 1 -GENETICS • Genetic Counsellors • Cancer • Genetics SECTION 2 – GENETIC TESTING • Genetic Testing (tissue vs germline) • How To Access Genetic Testing SECTION 3 – PROSTATE CANCER GENETICS • Genes Connected to Prostate Cancer • How Genetic Testing Impacts Prostate Cancer Risk, Aggressiveness, Treatment SECTION 4 – OTHER PROSTATE CANCER RISK FACTORS • Family History • Ancestry
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- 6. Genes mutation = pathogenicvariant mutation http://www.encognitive.com/node/10741
- 7. Inheriting a PathogenicVariant
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- 11. Germline Testing TissueTesting Cancer Genetic Testing • Saliva sample • Blood sample • Mutation present or absent (generally) • Tumour sample • Liquid biopsy • Mutation always present https://www.precisionmed.ch/en/what-is-cancer/
- 12. Germline Genetic TestResults https://sanogenetics.com/blog/what-is-a-genetic-variant-of-uncertain-significance/ common uncommon rare Mutation = likely pathogenic / pathogenic variant
- 14. Why Should ProstateCancer Patients Get Genetic Testing? – Understand prostate cancer risk? – Potential risk for other cancers? (eg. colon cancer, breast cancer) – Cascade testing for family members? (eg. siblings, children) – Prostate cancer aggressiveness – Recommendations for clinical treatment of localized disease – Active Surveillance – Surgery – Radiation – Eligibility for PARPi Clinical Trials
- 15. Emily Thain, MSc,CGC Genetic Counsellor, Princess Margaret Cancer Centre Traditional Model Mainstream Model Genetic Testing Process
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- 17. Genetic Non-Discrimination Act(GNA) GNA is a law that protects you from use of genetic test results in certain settings. GNA prevents the following from using genetic test results against you: • Insurance companies • Life insurance, Critical illness insurance • Federal government-regulated employers GNA does NOT prevent insurers/employers from using… • information about your personal history of cancer • information about your family history cancer
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- 20. PMID: 2743384 11.8% 82/692people with metastatic prostate cancer inherited a germline mutation BRCA2 37 5.35% ATM 11 1.59% CHEK2 10 1.87% BRCA1 6 0.87%
- 21. Prostate Cancer Risk HOXB13+++ BRCA1 BRCA2 MLH1 MSH2 MSH6 PMS2 ATM CHEK2 PALB2
- 22. Prostate Cancer Risk HOXB13+++ BRCA1 + BRCA2 ++ MLH1 MSH2 MSH6 PMS2 ATM CHEK2 PALB2
- 23. Hereditary Breast/Ovarian Cancer SiteBRCA1 BRCA2 ATM CHEK2 PALB2 General Population Breast (female) 60%-72% 55%-69% 20%-40% 23%-27% 32%-53% 11-12% Ovarian 39%–58% 13%–29% 2%–3% N/A 3%-5% 1.3% Prostate 7%–26% 19%–61% increased risk increased risk increased risk 11.6% Pancreas ≤5% 5%–10% ~5%–10% N/A 2%-5% no data on SEER Breast (male) 0.2%-1.2% 1.8%-7.1% N/A N/A 0.9% ≤1% Colorectal N/A N/A N/A N/A N/A 4.2% Gastric? ?? ?? N/A N/A N/A 0.9%
- 24. Prostate Cancer Risk HOXB13+++ BRCA1 + BRCA2 ++ MLH1 ? MSH2 + MSH6 + PMS2 - ATM CHEK2 PALB2
- 25. Prostate Cancer Risk HOXB13+++ BRCA1 + BRCA2 ++ MLH1 ? MSH2 + MSH6 + PMS2 - ATM + CHEK2 PALB2
- 26. Prostate Cancer Risk HOXB13+++ BRCA1 + BRCA2 ++ MLH1 ? MSH2 + MSH6 + PMS2 - ATM + CHEK2 + PALB2
- 27. Prostate Cancer Risk HOXB13+++ BRCA1 + BRCA2 ++ MLH1 ? MSH2 + MSH6 + PMS2 - ATM + CHEK2 + PALB2 - 🤠
- 28. Prostate Cancer RiskAggressive? HOXB13 +++ ? BRCA1 + BRCA2 ++ MLH1 ? MSH2 + MSH6 + PMS2 - ATM + CHEK2 + PALB2 ?
- 29. Prostate Cancer RiskAggressive? HOXB13 +++ ? BRCA1 + ? BRCA2 ++ Y MLH1 ? MSH2 + MSH6 + PMS2 - ATM + CHEK2 + PALB2 ?
- 30. Prostate Cancer RiskAggressive? HOXB13 +++ ? BRCA1 + ? BRCA2 ++ Y MLH1 ? N MSH2 + ? MSH6 + ? PMS2 - - ATM + CHEK2 + PALB2 ?
- 31. Prostate Cancer RiskAggressive? HOXB13 +++ ? BRCA1 + ? BRCA2 ++ Y MLH1 ? N MSH2 + ? MSH6 + ? PMS2 - - ATM + ? CHEK2 + PALB2 ?
- 32. Prostate Cancer RiskAgressive? HOXB13 +++ ? BRCA1 + ? BRCA2 ++ Y MLH1 ? N MSH2 + ? MSH6 + N PMS2 - - ATM + ? CHEK2 + N PALB2 ?
- 33. Prostate Cancer RiskAgressive? HOXB13 +++ ? BRCA1 + ? BRCA2 ++ Y MLH1 ? N MSH2 + ? MSH6 + N PMS2 - - ATM + ? CHEK2 + N PALB2 ? Y?
- 34. Prostate Cancer RiskTreatment (AS/Sx/XRT) HOXB13 +++ - BRCA1 + ? BRCA2 ++ Y MLH1 ? - MSH2 + - MSH6 + - PMS2 - - ATM + ? CHEK2 + - PALB2 ? ?
- 35. Prostate Cancer RiskmPC HOXB13 +++ - BRCA1 + Y BRCA2 ++ Y MLH1 +/- MSH2 ++ MSH6 ++ PMS2 - ATM + Y CHEK2 + - Prostate Cancer Risk mPC HOXB13 +++ - BRCA1 + Y BRCA2 ++ Y MLH1 ? Y MSH2 + Y MSH6 + Y PMS2 - Y ATM + - CHEK2 + - PALB2 ? -
- 36. SECTION 4 Other Prostate CancerRisk Factors
- 37. Hereditary Cancer vsNot Hereditary Cancer
- 38. Heritability = proportionof variance in cancer risk due to genetic differences between people • Prospective study of 80,309 MZ and 123,382 same-sex DZ twins followed for a median of 32 years PMID: 26746459
- 39. Risk Group RR Brotherwith prostate cancer diagnosed at any age 2.84 Father with prostate cancer diagnosed at any age 2.12 One affected FDR diagnosed at any age 2.22 One affected SDR diagnosed at any age 1.88
- 40. West Africa • SierraLeone • Liberia • Ivory Coast • Ghana Caribbean • Trinidad & Tobago • Jamaica • Turks and Caicos • The Bahamas • Saint Vincent • Honduras • Haiti • Grenada • Barbados
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Editor's Notes
- #1 National, prostate cancer patients and caregivers Tumour vs somatic The Screen Project Blood vs saliva CHARM2
- #6 Explain that mutation is a change/mistake in a gene Mutations can be caused by errors in cell division or perhaps environment (radiation, chemicals, smoking)
- #9 Explain that mutation is a change/mistake in a gene Mutations can be caused by errors in cell division or perhaps environment (radiation, chemicals, smoking)