Deficient Mismatch Repair Represents a Distinct Molecular Feature of Early-Onset Colorectal Cancer in Chinese Single-Center Cohort.

Authors

Deng Tang, Zhigang Mao, Siqi Lan, Yali Song, Si Chen, Yuemei Chen, Mi Su, Yufei Tang, Chengyi Zhu, Ruiting Yan, Ji Zhang, Yufang Wang

Published in

International journal of cancer. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50 years, is increasing worldwide, with a similar trend emerging in China. However, the clinicopathological and mismatch repair features of EOCRC in Chinese patients remain insufficiently characterized. We retrospectively reviewed 23,414 colorectal neoplasia cases diagnosed at West China Hospital between November 2008 and June 2023. Among these, 4,159 colorectal cancer cases with complete immunohistochemical assessment of MLH1, PMS2, MSH2, and MSH6 were included in the primary analysis. Clinicopathological characteristics and mismatch repair status were compared between EOCRC and late-onset colorectal cancer (LOCRC), with additional stratification by documented family history. Multivariable logistic regression was used to evaluate the independent association between early-onset status and deficient mismatch repair (dMMR). Compared with LOCRC, EOCRC showed less favorable clinicopathological features, including higher proportions of poor differentiation, T4 tumors, nodal involvement, and advanced TNM stage. EOCRC also had a significantly higher prevalence of dMMR. In multivariable analysis, early-onset status was independently associated with dMMR in the overall cohort (adjusted OR, 2.27; 95% CI, 1.60-3.22; p < 0.001), and among patients without documented family history (adjusted OR, 1.95; 95% CI, 1.33-2.86; p < 0.001). Patterns of MMR protein loss differed according to documented family history status. In conclusion, EOCRC in this Chinese MMR-tested cohort was associated with more advanced clinicopathological features and a higher prevalence of dMMR, supporting routine MMR assessment in young patients with colorectal cancer.

PMID:
42538607
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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