Province-Wide Ascertainment of Lynch Syndrome in Manitoba

Heidi Rothenmund; Pascal Lambert; Deirdre Khan; Christina Kim; Bhavya Sharma; Kim Serfas; Bernard Chodirker; Harminder Singh

doi:10.1016/j.cgh.2023.10.005

Province-Wide Ascertainment of Lynch Syndrome in Manitoba

Clin Gastroenterol Hepatol. 2024 Mar;22(3):642-652.e2. doi: 10.1016/j.cgh.2023.10.005. Epub 2023 Oct 23.

Authors

Heidi Rothenmund¹, Pascal Lambert², Deirdre Khan², Christina Kim³, Bhavya Sharma⁴, Kim Serfas¹, Bernard Chodirker⁵, Harminder Singh⁶

Affiliations

¹ Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
² Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Manitoba, Canada.
³ Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Manitoba, Canada; Section of Hematology/Oncology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁴ Section of Gastroenterology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁶ Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Manitoba, Canada; Section of Hematology/Oncology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Section of Gastroenterology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: Harminder.singh@umanitoba.ca.

PMID: 37879520
DOI: 10.1016/j.cgh.2023.10.005

Abstract

Background & aims: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years.

Methods: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to 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 were stratified and compared before and after the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP vs clinic referrals (CRs).

Results: Between 2014 and 2021, 50 of 101 (49.5%) index cases were identified by the LSSP compared with 51 of 101 (50.5%) from CRs. The proportion of PMS2 variants was 34% (17 of 50) for LSSP index cases compared with 21.6% (11 of 51) for CRs from 2014 to 2021 (P < .001). Among CRs from 2014 to 2021, 24 of 51 (47.1%) families met the Amsterdam criteria, compared with 11 of 50 (22.0%) for the LSSP (P = .01). CGT occurred among 46.8% (95 of 203; average, 1.9 relatives/index) of first-degree relatives of CR index cases vs 36.5% (84 of 230; average, 1.7 relatives/index) of first-degree relatives of LSSP index cases (P = .03). Daughters were most likely to undergo CGT.

Conclusions: A tumor 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 with the screening program. These findings suggest a complementary role of these 2 ascertainment methods for Lynch syndrome.

Keywords: Cascade Testing; Colorectal Cancer; Endometrial Cancer; Genetic Testing; Universal Screening.

MeSH terms

Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
Colorectal Neoplasms, Hereditary Nonpolyposis* / epidemiology
Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
DNA Mismatch Repair
Genetic Testing / methods
Germ-Line Mutation
Humans
Manitoba / epidemiology
Retrospective Studies