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  1. 1. <ul><li>Cancer Answers is a series of free public lectures, presented by Cancer Care Nova Scotia , on a variety of cancer-related topics. The lectures, delivered by cancer experts, are designed to raise awareness and educate participants about issues related to prevention, screening, early diagnosis, treatment, survivorship and palliative care. </li></ul><ul><li>Following each lecture, the presentations are posted on the Cancer Care Nova Scotia website. </li></ul>
  2. 2. Hereditary Cancer Cancer Answers Cancer Care Nova Scotia May 20 th , 2008 Patricia Steele, MSc, CCGC, CGC Genetic Counsellor Maritime Medical Genetics Services IWK Health Centre and Genetic Testing
  3. 3. Outline <ul><li>Cell Growth and Development </li></ul><ul><li>Sporadic, Familial and Hereditary </li></ul><ul><li>Quick Genetics Review </li></ul><ul><li>Common Inherited Forms of Cancer </li></ul><ul><li>Genetic Assessment </li></ul><ul><li>Pros and Cons of Genetic Testing </li></ul>
  4. 4. Cell Growth and Development <ul><li>Many processes control cell growth and cell division </li></ul><ul><li>Cell division – making an exact copy of itself </li></ul><ul><li>DNA content doubled and then divided into both cell copies </li></ul><ul><li>Many genes involved </li></ul>
  5. 5. Cancer – Abnormal Cell Growth <ul><li>Cancer is the abnormal growth of cells during cell division </li></ul><ul><li>Cancer results from defects or damage in genes (DNA) involved in cell division </li></ul><ul><li>Several of these controls need to be damaged before a cell becomes cancerous </li></ul>
  6. 6. Cancer: When is it Inherited? <ul><li>~ 85% Sporadic (by chance) </li></ul><ul><li>~ 10% Familial </li></ul><ul><li>~ 5% Hereditary </li></ul>
  7. 7. Sporadic Cancer History <ul><li>Occurs by chance alone </li></ul><ul><li>1 or 2 individuals at typical age of onset </li></ul><ul><li>Not an inherited pattern </li></ul><ul><li>Relatives usually not at increased chance to develop cancer (general population chance) </li></ul><ul><li>Genetic testing not beneficial </li></ul>
  8. 8. Familial Cancer History <ul><li>Not the same type of cancer or related cancers </li></ul><ul><li>Average age of onset </li></ul><ul><li>No clear pattern of inheritance </li></ul><ul><li>May be due to shared factors (genes/environment/lifestyle) </li></ul><ul><li>Relatives have slightly increased chance of cancer </li></ul><ul><li>Genetic testing not beneficial </li></ul>
  9. 9. <ul><li>Many family members with the same or related cancers </li></ul><ul><li>Earlier ages of onset </li></ul><ul><li>One person may have more than one type cancer </li></ul><ul><li>Two or more generations affected </li></ul><ul><li>Genetic testing may be beneficial </li></ul>Hereditary Cancer History
  10. 10. Quick Genetic Review
  11. 11. The genome is like an encyclopedia...
  12. 12. A Gene is Like A Recipe for Making A Specific Protein
  13. 13. Everyone Has Changes In Their DNA <ul><li>Some changes have no medical effect </li></ul><ul><li>A harmful change in the DNA is called a ‘mutation’ </li></ul><ul><li>Mutations prevent the gene from working properly </li></ul>
  14. 14. Some Gene Mutations Cause A Loss of Function of the Gene <ul><li>Tumor suppressor genes instruct the cells to stop cell division </li></ul><ul><li>A mutation in a tumour suppressor gene is like having the brakes fail in your car </li></ul>
  15. 15. Some Gene Mutations Cause A Gain of Function of the Gene <ul><li>Oncogenes -initiate cellular division </li></ul><ul><li>(promote cell growth) </li></ul><ul><li>A mutation in an oncogene can speed up cell growth </li></ul><ul><li>Like pressing on the gas peddle of a car all the time (out of control) </li></ul>
  16. 16. Some Genes Repair DNA Errors (The DNA Mechanics)
  17. 17. Many Cellular Changes Involved
  18. 18. Inherited or Acquired Gene Mutations
  19. 19. Dominant Inheritance <ul><li>does not cause cancer </li></ul><ul><li>increases risk for developing cancer </li></ul>
  20. 20. Inherited Cancer Syndromes <ul><li>Hereditary component in ~ 5-15% of these very common types of cancers </li></ul><ul><ul><li>Colorectal Cancer </li></ul></ul><ul><ul><li>Breast/Ovarian Cancer </li></ul></ul><ul><li>Less common inherited cancer syndromes </li></ul><ul><ul><li>Hereditary Diffuse Gastric Cancer (HDGC) </li></ul></ul><ul><ul><li>Multiple Endocrine Neoplasia (MEN) </li></ul></ul><ul><ul><li>Li-Fraumeni syndrome </li></ul></ul><ul><ul><li>Von Hippel Lindau syndrome </li></ul></ul>
  21. 21. Inherited Colon Cancer <ul><li>Hereditary nonpolyposis colon cancer (HNPCC) </li></ul><ul><li>Familial adenomatous polyposis (FAP) </li></ul><ul><ul><li>~ 1% of hereditary colon cancer </li></ul></ul><ul><ul><li>Attenuated FAP (later age onset) </li></ul></ul><ul><li>MYH Associated Polyposis (MAP) </li></ul><ul><ul><li>~ 1% of hereditary colon cancers </li></ul></ul>
  22. 22. Hereditary Nonpolyposis Colon Cancer (HNPCC) <ul><li>Small number of polyps </li></ul><ul><li>Many DNA repair genes involved </li></ul><ul><li>Also called Lynch syndrome </li></ul><ul><ul><li>Type 1– Colon cancer </li></ul></ul><ul><ul><li>Type 2- </li></ul></ul><ul><ul><ul><li>Colon </li></ul></ul></ul><ul><ul><ul><li>Uterine, breast, pancreas, ovarian, bile duct </li></ul></ul></ul>
  23. 23. Familial Adenomatous Polyposis (FAP) <ul><li>~1% hereditary colon cancers </li></ul><ul><li>Hundreds of polyps </li></ul><ul><ul><li>Onset of polyps - teen years </li></ul></ul><ul><ul><li>Start screening no later than age 10 </li></ul></ul><ul><ul><li>Average age of cancer diagnosis – age 38 </li></ul></ul><ul><li>If no treatment – v. high likelihood of cancer </li></ul><ul><li>Attenuated FAP (AFAP) </li></ul><ul><ul><li>multiple polyps </li></ul></ul><ul><ul><li>Later age onset of colon cancer (<60 years) </li></ul></ul><ul><li>APC gene - good detection rate (~80-90%) </li></ul>
  24. 24. MYH-Associated Polyposis (MAP) <ul><li>Families with multiple polyps (like AFAP) </li></ul><ul><ul><li>But do not identify APC gene mutation </li></ul></ul><ul><li>2002 - new gene found – MYH </li></ul><ul><ul><li>~10% of AFAP-like families </li></ul></ul><ul><li>Screening beginning in 20’s </li></ul><ul><li>Recessive inheritance </li></ul><ul><ul><li>inherit 2 non-working genes </li></ul></ul><ul><ul><li>See in siblings </li></ul></ul>
  25. 25. Routine Screening ? Increased Screening? <ul><li>Most people: </li></ul><ul><ul><li>~ 5-6% lifetime chance of colon cancer </li></ul></ul><ul><ul><li>Later ages of onset </li></ul></ul><ul><ul><li>> 10 years from polyp to bowel cancer </li></ul></ul><ul><li>If no family history of colon cancer then general population screening is appropriate </li></ul><ul><ul><li>Colon screening after age 50 </li></ul></ul><ul><ul><li>Fecal Occult Blood Test (FOBT) </li></ul></ul><ul><li>If family history or inherited predisposition then more direct screening is appropriate </li></ul><ul><ul><li>Colon screening with more direct test (i.e. colonoscopy) </li></ul></ul><ul><ul><li>Start 5-10 years earlier than onset in the family </li></ul></ul>
  26. 26. Sporadic Breast Cancer <ul><li>All women have a 1 in 9 (11%) lifetime chance of developing breast cancer </li></ul><ul><ul><li>usually over 65 years-of-age </li></ul></ul><ul><li>Most women over-estimate their risk for breast cancer and genetic testing is not beneficial or appropriate for most women </li></ul>
  27. 27. Hereditary Breast/Ovarian Cancer <ul><li>Family History </li></ul><ul><ul><li>How closely related - 1 st or 2 nd degree relatives </li></ul></ul><ul><li>Early ages of onset </li></ul><ul><ul><li>Average age of onset ~39-44years </li></ul></ul><ul><li>More than one primary cancer </li></ul><ul><li>Ancestry (Icelandic, Ashkenazi Jewish) </li></ul><ul><li>Laterality (one side or both sides) </li></ul><ul><li>Male breast cancer </li></ul>
  28. 28. Br east Ca ncer Genes (BRCA1 and BRCA2) <ul><li>Increased Predisposition but not a diagnosis </li></ul><ul><li>If BRCA mutation found: </li></ul><ul><ul><li>Genetic testing is available for family members </li></ul></ul><ul><li>If no BRCA mutation found: </li></ul><ul><ul><li>No genetic test available for family members </li></ul></ul>
  29. 29. If ‘Positive’ for BRCA Mutation <ul><li>Additional Options to consider : </li></ul><ul><ul><li>Increased screening </li></ul></ul><ul><ul><ul><li>Clinical breast exams 2 times a year </li></ul></ul></ul><ul><ul><ul><li>MRI </li></ul></ul></ul><ul><ul><ul><li>Mammograms start 5-10 years earlier than onset in family </li></ul></ul></ul><ul><ul><li>Lifestyle changes ? </li></ul></ul><ul><ul><ul><li>Quit smoking </li></ul></ul></ul><ul><ul><ul><li>Healthy eating and exercise? </li></ul></ul></ul><ul><ul><li>Medical prevention </li></ul></ul><ul><ul><li>Prophylactic surgery </li></ul></ul><ul><ul><ul><li>Mastectomy </li></ul></ul></ul><ul><ul><ul><li>Oophorectomy </li></ul></ul></ul>
  30. 30. Breast Cancer Genes Gene BRCA1 (breast, ovarian, prostate) BRCA2 (male/female breast, ovarian) TP53 (breast, brain, sarcoma, leukemia, adrenal) PTEN ( breast, thyroid, oral, intestinal) ATM (breast, ionizing radiation sensitivity) Undiscovered genes Contribution to Hereditary Breast Cancer 20%–40% 10%–30% <1% <1% <1% 30%–70%
  31. 31. Hereditary Diffuse Gastric Cancer (HDGC) <ul><li>5%-10% of all gastric (stomach) cancers are familial </li></ul><ul><li>Gastric cancer seen in several other cancer syndromes (i.e. HNPCC) </li></ul><ul><li>Diffuse - Different pathology (not a tumour mass) </li></ul><ul><li>Stomach wall – rubbery, hard, thickened </li></ul><ul><li>Average age onset – 38 years </li></ul><ul><li>Also see: </li></ul><ul><ul><li>Lobular breast cancer </li></ul></ul><ul><ul><li>Colon cancer </li></ul></ul><ul><li>CDH1 gene </li></ul>
  32. 33. Tools for Genetic Assessment <ul><li>Family history best predictor </li></ul><ul><ul><li>Maternal & paternal history </li></ul></ul><ul><ul><ul><li>How closely related </li></ul></ul></ul><ul><ul><li>Specific types and specific patterns </li></ul></ul><ul><li>Clinical and pathology information </li></ul><ul><ul><li>Tumour pathology </li></ul></ul><ul><ul><ul><li>Breast cancer - lobular or infiltrating ductal </li></ul></ul></ul><ul><ul><ul><li>Colon cancer – many polyps or a few polyps </li></ul></ul></ul><ul><ul><li>Confirming the diagnosis </li></ul></ul><ul><ul><ul><li>Was it ovarian cancer or cervical cancer? </li></ul></ul></ul>
  33. 34. Multiple Endocrine Neoplasia (MEN) <ul><li>Multiple endocrine neoplasia type 1 (MEN1) </li></ul><ul><ul><li>Pituitary, pancreas, parathyroid tumors </li></ul></ul><ul><ul><li>MEN1 gene (chromosome 11) </li></ul></ul><ul><li>Multiple endocrine neoplasia type 2 (MEN2) </li></ul><ul><ul><li>Medullary thyroid cancer (~75% sporadic) </li></ul></ul><ul><ul><li>Adrenal gland tumours (pheochromocytoma) </li></ul></ul><ul><ul><li>Parathyroid disease </li></ul></ul><ul><ul><li>RET gene (chromosome 10) </li></ul></ul>
  34. 35. Genetic Counselling….. What to Expect <ul><li>Before an appointment : </li></ul><ul><li>Your homework: </li></ul><ul><ul><li>Family History Questionnaire </li></ul></ul><ul><ul><li>Medical records </li></ul></ul><ul><li>Our homework: </li></ul><ul><ul><li>Family specific genetic assessment </li></ul></ul><ul><ul><li>Select specific genetic test – if available </li></ul></ul>
  35. 36. Not Always An Obvious Pattern- Need the Full (Family) Picture <ul><li>Li-Fraumeni syndrome </li></ul><ul><ul><li>Breast cancer </li></ul></ul><ul><ul><li>Other cancers in the family </li></ul></ul><ul><ul><ul><li>Bone cancer (Osteosarcoma) </li></ul></ul></ul><ul><ul><ul><li>Soft tissue cancers (Sarcoma) </li></ul></ul></ul><ul><ul><ul><li>Leukemia </li></ul></ul></ul><ul><li>Von Hippel Lindau syndrome </li></ul><ul><ul><li>Benign tumours of brain/spine (Hemangioblastoma) </li></ul></ul><ul><ul><li>Kidney cancer (renal cell) </li></ul></ul><ul><ul><li>Adrenal glands </li></ul></ul>
  36. 37. Genetic Testing Limitations <ul><li>Not a ‘yes’ or ‘no’ answer </li></ul><ul><ul><li>Not 100% detection rate </li></ul></ul><ul><ul><li>Technical limitations? Other genes to be discovered? </li></ul></ul><ul><ul><li>Interpretation of result is unclear </li></ul></ul><ul><li>Not all at-risk families are able to be tested </li></ul><ul><ul><li>1 st need to test an appropriate, living affected individual </li></ul></ul><ul><li>Based on referral criteria for BRCA testing: </li></ul><ul><ul><li>~ 10% of individuals tested have mutation found </li></ul></ul><ul><ul><li>~90% results - ‘no mutation found’ </li></ul></ul>Dx 35 D 43 yr
  37. 38. Some Benefits of Genetic Testing <ul><li>Identifies high-risk individuals </li></ul><ul><li>May help in decision-making (medical/lifestyle) </li></ul><ul><li>Screening and prevention strategies </li></ul><ul><li>May explain cancer pattern if mutation found </li></ul><ul><li>May have positive impact family relationships </li></ul><ul><li>May relieve anxiety </li></ul>
  38. 39. Some Reasons Not to Have Genetic Testing <ul><li>You “wouldn’t do anything different” </li></ul><ul><li>Genetic testing does not detect all mutations </li></ul><ul><li>Despite screening options, the cancer risk not zero </li></ul><ul><li>Privacy, insurance or employment concerns? </li></ul><ul><li>May increase fear/anxiety – open a Pandora’s Box </li></ul><ul><li>May negatively impact family relationships </li></ul><ul><li>Guilt of ‘passing it on’ </li></ul>
  39. 40. Review –The Clues That Cancer Might be Inherited? <ul><li>Many individuals in a family </li></ul><ul><ul><li>On the same side of the family </li></ul></ul><ul><li>Affected over many generations </li></ul><ul><ul><li>Three generation family history </li></ul></ul><ul><li>Early ages of onset </li></ul><ul><ul><li>Often before age 50 </li></ul></ul><ul><li>Specific patterns and related types of cancer </li></ul>
  40. 41. Review –What’s Right for You? Family Hx Assessment Personalized screening and prevention recommendations Referral for Genetic Evaluation with personalized screening and prevention recommendations Standard screening and prevention recommendations Intervention Average (1 in 9) Sporadic Moderate (Familial) High (Hereditary ) Genetic Risk
  41. 42. Some Things to Remember <ul><li>Everyone has 6-12 genes that don’t work properly – most not a health concern </li></ul><ul><li>The chance of developing cancer is never 100% and it is never 0% </li></ul><ul><li>Family history is important </li></ul><ul><li>But Family is more important!! </li></ul>
  42. 43. <ul><li>Thank You! </li></ul><ul><li>Patricia Steele </li></ul><ul><li>Maritime Medical Genetics </li></ul><ul><li>IWK Health Centre </li></ul><ul><li>Halifax, NS </li></ul><ul><li>902-470-8754 </li></ul>