Literature DB >> 31470178

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

Anne Goverde1, Ellis L Eikenboom1, Ellemieke L Viskil2, Marco J Bruno3, Michael Doukas4, Winand N M Dinjens4, Erik Jan Dubbink4, Ans M W van den Ouweland2, Robert M W Hofstra2, Anja Wagner2, Manon C W Spaander5.   

Abstract

BACKGROUND & AIMS: Patients 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.
METHODS: We 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).
RESULTS: At 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, of which 3 from pancreatic cancer).
CONCLUSIONS: No 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.
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Colon; Genetics; Hereditary Cancer Prevention; MMR

Year:  2019        PMID: 31470178     DOI: 10.1016/j.cgh.2019.08.043

Source DB:  PubMed          Journal:  Clin Gastroenterol Hepatol        ISSN: 1542-3565            Impact factor:   11.382


  3 in total

Review 1.  Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome.

Authors:  Hans F A Vasen
Journal:  Fam Cancer       Date:  2021-01-19       Impact factor: 2.375

2.  Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome.

Authors:  Fay Kastrinos; Myles A Ingram; Elisabeth R Silver; Aaron Oh; Monika Laszkowska; Anil K Rustgi; Chin Hur
Journal:  Gastroenterology       Date:  2021-04-09       Impact factor: 33.883

3.  Cost-effectiveness analysis of genetic diagnostic strategies for Lynch syndrome in Italy.

Authors:  Roberta Pastorino; Michele Basile; Alessia Tognetto; Marco Di Marco; Adriano Grossi; Emanuela Lucci-Cordisco; Franco Scaldaferri; Andrea De Censi; Antonio Federici; Paolo Villari; Maurizio Genuardi; Walter Ricciardi; Stefania Boccia
Journal:  PLoS One       Date:  2020-07-01       Impact factor: 3.240

  3 in total

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