Province-Wide Ascertainment of Lynch Syndrome in Manitoba

Abstract

Background & AimsWe describe the experience of Lynch Syndrome (LS) diagnosis in the province of Manitoba, Canada over the last twenty years. MethodsWe performed a retrospective review of charts from the provincial Genetics clinic from January 1, 2000-May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT). Data was stratified and compared pre and post the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP versus clinic referrals (CR). ResultsBetween 2014-2021, 50/101 (49.5%) index cases were identified by the LSSP compared to 51/101 (50.5%) from CR. The proportion of PMS2 variants was 34% (17/50) for LSSP index cases compared to 21.6% (11/51) for CR 2014-2021 (p<0.001). Amongst CRs 2014-2021, 24/51 (47.1%) of families met the Amsterdam criteria, compared to 11/50 (22.0%) for the LSSP (p= 0.01). CGT occurred among 46.8% (95/203; average 1.9 relatives/index) of first-degree relatives (FDRs) of CR index cases versus 36.5% (84/230; average 1.7 relatives/index) of FDRs of LSSP index cases (p=0.03). Daughters were most likely to undergo CGT. ConclusionsA tumour screening program is more effective at detecting individuals with lower penetrant gene variants and families who do not meet traditional family history-based criteria. Cascade genetic testing is higher among clinic referrals compared to the screening program. These findings suggest a complementary role of these two ascertainment methods for Lynch syndrome.