Colorectal cancer and advanced adenoma characteristics according to causative mismatch repair gene variant in Japanese colorectal surveillance for Lynch syndrome

J Gastroenterol. 2024 Aug;59(8):699-708. doi: 10.1007/s00535-024-02128-5. Epub 2024 Jun 21.

Abstract

Background: The optimal interval of colonoscopy (CS) surveillance in cases with Lynch syndrome (LS), and stratification according to the causative mismatch repair gene mutation, has received much attention. To verify a feasible and effective CS surveillance strategy, we investigated the colorectal cancer (CRC) incidence at different intervals and the characteristics of precancerous colorectal lesions of LS cases.

Methods: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path_) were analyzed according to the data of 1,756 registered CS.

Results: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path_MLH1, path_MSH2, and path_MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path_MSH6 cases as compared with that for path_MLH1 and path_MSH2 cases.

Conclusions: In cases with path_MLH1, path_MSH2, and path_MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path_MSH6 cases could be stratified with path_MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset.

Keywords: Advanced adenoma; Interval colorectal cancer; Lynch syndrome; Quality indicator; Surveillance stratification.

Publication types

  • Multicenter Study

MeSH terms

  • Adenoma* / epidemiology
  • Adenoma* / genetics
  • Adenoma* / pathology
  • Adult
  • Aged
  • Colonoscopy*
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / epidemiology
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
  • DNA Mismatch Repair* / genetics
  • DNA-Binding Proteins / genetics
  • Early Detection of Cancer / methods
  • East Asian People
  • Female
  • Germ-Line Mutation
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • MutL Protein Homolog 1* / genetics
  • MutS Homolog 2 Protein* / genetics
  • Retrospective Studies
  • Time Factors

Substances

  • MutL Protein Homolog 1
  • MLH1 protein, human
  • MutS Homolog 2 Protein
  • MSH2 protein, human
  • DNA-Binding Proteins
  • G-T mismatch-binding protein