47 - Differences in Lynch Syndrome Colonoscopy Surveillance by Pathogenic Variant

Elena Gibson, MD¹, Haojia Li, MS¹, Judith Staub, MD¹, Megan Keener, CCRC², Priyanka Kanth, MD, MS^3
1University of Utah, Salt Lake City, UT; ²Huntsman Cancer Institute, Salt Lake City, UT; ³MedStar Georgetown University Hospital, Washington, DC

Introduction: Lynch syndrome is caused by pathogenic variants in 4 mismatch repair genes: MLH1, MSH2, MSH6, & PMS2. There is limited data on differences in endoscopic surveillance by pathogenic variant, and surveillance for colorectal cancer (CRC) with colonoscopy every 1-2 years is recommended for all patients. It is not known if occurrence of colonic lesions differs by mutation status. We aimed to evaluate colonoscopy surveillance outcomes in patients with Lynch syndrome overall and compare findings between patients by variant.

Methods: We retrospectively reviewed colonoscopy results in patients with Lynch syndrome at our institution. Of 221 patients identified by participation in the Hereditary Gastrointestinal Cancer Registry (HGCR), 101 were included after excluding those without >1 colonoscopy available and 1 patient with a hereditary polyposis syndrome. Baseline variables and surveillance results from diagnosis to May 2020 were compared by variant (MLH1, MSH2, MSH6, PMS2). Primary outcomes included development and recurrence of adenoma, CRC, high grade dysplasia (HGD), advanced adenoma (AA), and sessile serrated lesions (SSL). Logistic regression analyses were completed to evaluate the relationship between pathogenic variant and development or recurrence of adenoma, SSL, and AA/HGD/CRC. A survival analysis evaluated the development of the primary outcomes in patients with > 2 colonoscopies.

Results: 327 colonoscopies were reviewed. Baseline characteristics did not differ by variant, and patients with MLH1 had more colonoscopies completed (Table 1). PMS2 was associated with decreased odds of AA/HGD/CRC development compared to MLH1 (OR .102, 95% CI .013-.507) and adenoma development compared to MSH2 (OR .240, 95% CI .057-.902). Among those with >2 colonoscopies (n=71), there was no significant difference in adenoma or AA/HGD/CRC development, but MSH2 had a lower risk of SSL compared to MLH1 (HR .053, 95% CI .004-.762) and MSH6 (HR .067, 95% CI .005-.861). For recurrence, PMS2 had a lower risk of adenoma recurrence compared to MLH1 (OR=.021, 95% CI .021-.001) and MSH2 (OR .084, 95% CI .006-.726). Similarly, MSH6 (OR .068, CI .004-.652) had a lower risk of adenoma recurrence compared to MLH1.

Discussion: Surveillance colonoscopy outcomes, including SSL risk, differed in patients with Lynch Syndrome based on the pathogenic variant present. These findings suggest the need to further evaluate appropriate surveillance intervals based on variant.



Disclosures:


Elena Gibson, MD¹, Haojia Li, MS¹, Judith Staub, MD¹, Megan Keener, CCRC², Priyanka Kanth, MD, MS³, 47, Differences in Lynch Syndrome Colonoscopy Surveillance by Pathogenic Variant, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.