Yield of Lynch Syndrome Surveillance for Patients With Pathogenic Variants in DNA Mismatch Repair Genes

AbstractBackground & AimsPatients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with...

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Published in:	Clinical gastroenterology and hepatology Vol. 18; no. 5; pp. 1112 - 1120.e1
Main Authors:	Goverde, A, Eikenboom, E.L, Viskil, E.L, Bruno, M.J, Doukas, M, Dinjens, W.N.M, Dubbink, H.J, van den Ouweland, A.M.W, Hofstra, R.M.W, Wagner, A, Spaander, M.C.W
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-05-2020
Subjects:	Colon Gastroenterology and Hepatology Genetics Hereditary Cancer Prevention MMR colon hereditary cancer prevention genetics MMR Hereditary Cancer Prevention CRC LS Genetics Colon IQR MAP
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Summary:	AbstractBackground & AimsPatients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with these variants in MLH1, MSH2, MSH6, and PMS2. MethodsWe analyzed data on colonoscopy surveillance, including histopathology analysis, from all patients diagnosed with Lynch syndrome (n=264) at a single center. We compared the development of (advanced) adenomas and CRC among patients with pathogenic variants in the DNA mismatch repair genes MLH1 (n=55), MSH2 (n=44), MSH6 (n=143), or PMS2 (n=22) over 1836 years of follow-up (median follow-up of 6 years per patient). ResultsAt first colonoscopy, CRC was found in 8 patients. During 916 follow-up colonoscopies, CRC was found in 9 patients. No CRC was found in patients with variants in MSH6 or PMS2 over the entire follow-up period. There were no significant differences in the number of colonoscopies with adenomas or advanced adenomas among the groups. The median time of adenoma development was 3 years (IQR, 2–6 years). There were no significant differences in time to development of adenoma. However, patients with variants in MSH6 had a significant longer time to development of advanced neoplasia (advanced adenoma or CRC) than patients in the other groups. Six carriers died during follow up (5 from cancer, 3 from pancreatic cancer). ConclusionsNo CRC was found during follow-up of patients with Lynch syndrome carrying pathogenic variants in MSH6; advanced neoplasia developed over shorter follow-up time periods in patients with pathogenic variants in MLH1 or MSH2. The colonoscopy interval for patients with pathogenic variants in MSH6 might be increased to 3 years from the regular 2-year interval.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1542-3565 1542-7714
DOI:	10.1016/j.cgh.2019.08.043