Colon Cancer. The Ins and Outs of Lynch Syndrome. Nancy Rodenhiser, Genetic Counsellor, LHSC Genetics Education Day, October 22, 2014

Transcription

1 Colon Cancer The Ins and Outs of Lynch Syndrome Nancy Rodenhiser, Genetic Counsellor, LHSC Genetics Education Day, October 22, 2014

2 Colon Cancer The Ins and Outs of Lynch Syndrome Presenter Disclosure: Ms. Nancy Rodenhiser has no potential for conflict of interest with this presentation.

3 Objectives understand the general features of hereditary colon cancer syndromes explore the potential pros/cons and limitations of genetic testing for hereditary colon cancer awareness of available cancer surveillance and risk reduction strategies for patients at increased risk

4 Colorectal cancer Sporadic (65% 85%) Rare CRC syndromes (Peutz Jegher, MAP) (<0.1%) Familial adenomatous polyposis (FAP) (1 2%) Familial (10% 30%) Lynch syndrome (HNPCC) (5 7%) 4 mismatch repair genes [MLH1, MSH2, MSH6, PMS2] Adapted from Burt RW et al. Prevention and Early Detection of CRC, 1996

5 When is Lynch syndrome suspected? family history includes: more family members with colon cancer than expected, over several generations (same side of family) younger agesat diagnosis (i.e. less than age 50) multiple primary cancers in one or more family members (i.e. colon + uterine ca in one person) overall pattern of cancer in family (e.g. colorectal, endometrial, ovarian, stomach, hepatobiliary tract, ureter, brain, sebaceous adenoma/carcinoma) multiple polyps

6 Sporadic cancer Colon 70 Colon 57

7 Hereditary cancer PANC 60 CRC 35 CRC 58 UTER 42 BR 46 UTER 63

8 Lynch Syndrome Genetic Testing Benefits improved cancer risk management relief from uncertainty and anxiety about cancer risk for self and children information for individual and family members lifestyle decision making Risks uncertain significance of some mutations a negative result does not rule out risk in affected patient (uninformative) discrimination concerns (life insurers, employers) change in family dynamics

9 Ideally, begin testing on an affected family member (best to test) Colon 42 test first Colon 38 d.45 Colon 45 person seeking counselling (proband) if a mutation is found in affected parent, carrier testing becomes available and informative for other affected/unaffected family members

10 Testing Criteria Amsterdam Vasen et al Gastroenterology.

11 Testing Criteria Bethesda

12 Ontario MOH Lynch Syndrome Genetic Testing Criteria 3 or more relatives with verified CRC in family, and/or at least one case of CRC and other Lynchassociated tumour at least two successive generations affected, and one should be a 1 st degree relative of the other two at least one diagnosis before age 50 CRC diagnosed < age 35 multiple primary CRC or CRC and other Lynchassociated tumour in same person 2 cases CRC or CRC and other Lynch associated tumour, both diagnosed < age 50, in 1 st or 2 nd degree relatives March, 2006

13 Lynch Testing Strategy > 25% of individuals with Lynch Syndrome are not going to meet Amsterdam or Bethesda criteria universal tumour testing on all newly diagnosed colorectal and endometrial cancers with the intent to reduce cancer incidence and mortality due to Lynch syndrome age cut off? Cancer Care Ontario currently reviewing Immunohistochemistry for MMR proteins on all colorectal cancers diagnosed in patients age 60 and under

14 Cancer Site General Population Risk Lynch Syndrome Risk Colorectal 6 % Up to 80 % Endometrial 2 % % Ovarian 1 2 % 3 13 % Gastric 2 13 % Urinary tract 1 12 % Brain 1 4 % Bile duct/gall bladder < 2 % 2 % Small bowel 4 7 % > 1 cancer at diagnosis 7 10 % Obermair et al Int J Cancer.; Vasen et al J Med Genetics.

15 Cancer Surveillance Strategy Colonoscopy every 1 2 years, beginning at age 25 (or 5 10 years before the youngest diagnosis in the family, whichever is earlier) Annual gynecologic examination and prompt investigation into any unusual bleeding between menstrual periods or after menopause Annual endometrial biopsy with transvaginal ultrasound can be considered: begin at age if the family history includes endometrial cancer; or at age 35 if no endometrial cancer the effectiveness of this approach to screening has not been proven No standard screening recommendations for other cancers associated with Lynch syndrome; advise as per family history (i.e. upper endoscopy if gastric cancer present) Weissman et al J Genet Couns.

16 Summary Lynch syndrome is a hereditary predisposition to various types of cancer due to gene mutations in the DNA mismatch repair pathway (MLH1, MSH2, MSH6, PMS2) Previous clinical criteria miss at least 25% of Lynch cases Identification is key to cancer prevention & early detection start with thorough family history refer for genetic counselling and risk assessment IHC testing of incident colon/endometrial cancers appears to be a cost effective screening strategy, with potentially significant impact on morbidity and mortality enhanced cancer screening and prevention strategies are effective in individuals with Lynch syndrome