Background: Identifying genetic disease-susceptible individuals through population screening is considered as a promising approach for disease prevention. DNA mismatch repair (MMR) genes including MLH1, MSH2, MSH6 and PMS2 play essential roles in maintaining microsatellite stability through DNA mismatch repair, and pathogenic variation in MMR genes causes microsatellite instability and is the genetic predisposition for cancer as represented by the Lynch syndrome. While the prevalence and spectrum of MMR variation has been extensively studied in cancer, it remains largely elusive in the general population. Lack of the knowledge prevents effective prevention for MMR variation-caused cancer. In the current study, we addressed the issue by using the Chinese population as a model.

Methods: We performed extensive data mining to collect MMR variant data from 18 844 ethnic Chinese individuals and comprehensive analyses for the collected MMR variants to determine its prevalence, spectrum and features of the MMR data in the Chinese population.

Results: We identified 17 687 distinct MMR variants. We observed substantial differences of MMR variation between the general Chinese population and Chinese patients with cancer, identified highly Chinese-specific MMR variation through comparing MMR data between Chinese and non-Chinese populations, predicted the enrichment of deleterious variants in the unclassified Chinese-specific MMR variants, determined MMR pathogenic prevalence of 0.18% in the general Chinese population and determined that MMR variation in the general Chinese population is evolutionarily neutral.

Conclusion: Our study provides a comprehensive view of MMR variation in the general Chinese population, a resource for biological study of human MMR variation, and a reference for MMR-related cancer applications.