Risk Factors for Gastric Cancer in Patients with Lynch Syndrome: A Systematic Review and Meta-analysis.

Abstract

Lynch syndrome (LS) is an inherited disorder associated with an increased risk of colorectal and extracolonic malignancies, including gastric cancer (GC). This study quantifies the association between specific risk factors and GC development in patients with LS. We searched the PubMed and Scopus databases for prospective and retrospective cohort studies that evaluated patients with genetically confirmed LS and reported associations between demographic, clinical, or genetic characteristics and GC. We conducted a meta-analysis to pool risk ratios (RR) for key risk factors, including sex, genetic mutations, family history of GC, and Helicobacter pylori (HP) infection. We assessed heterogeneity using Cochran's Q test and the I² statistic. A total of 14 studies comprising 29,170 patients with LS met the inclusion criteria, of which 13 were included in the meta-analysis. Male sex (RR 2.8; 95% CI 2.2, 3.6; p < 0.001; I² = 0%), MLH1 (RR 1.8; 95% CI 1.4, 2.3; p < 0.001; I² = 0%) and MSH2 variants (RR 2.5; 95% CI 2.0, 3.2; p < 0.001; I² = 0%), family history of GC (RR 3.5; 95% CI 2.0, 5.8; p < 0.001; I² = 0%), and HP infection (RR 2.8; 95% CI 1.2, 6.8; p = 0.023; I² = 12.8%) were associated with increased GC risk. In contrast, the MSH6 variant was associated with lower GC risk (RR 0.6; 95% CI 0.4, 0.8; p = 0.006; I² = 0%). Our findings confirm that male sex, MLH1 and MSH2 variants, family history of GC, and HP infection are significant risk factors for GC in individuals with LS. These findings support the need for individualized surveillance strategies and targeted risk-reduction measures to improve early detection and patient outcomes.