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

Abstract

Background: Lynch Syndrome (LS) is an inherited disorder associated with increased risk of colorectal and extracolonic malignancies including gastric cancer (GC). This systematic review and meta-analysis aimed to quantify the association between risk factors and GC development in individuals with LS. Methods: A systematic literature search was conducted in PubMed and Scopus. We included prospective and retrospective cohort studies that assessed patients with genetically confirmed LS and reported the association between demographic, clinical, or genetic characteristics and GC. We performed meta-analysis of pooled risk ratios (RR) for key risk factors, including sex, genetic mutations, family history of GC, and Helicobacter pylori (HP) infection. Heterogeneity was assessed using Cochran's Q test and the I² statistic. Results: Fourteen studies, comprising 29,170 patients with LS, met the inclusion criteria, of which 13 included in 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. The MSH6 variant was associated with lower GC risk (RR=0.6; 95%CI=0.4; 0.8; p=0.006; I2=0%). Discussion: This study confirms male sex, MLH1 and MSH2 variants, family history of GC, and HP infection as significant risk factors for GC in individuals with LS. These findings emphasize the need for individualized surveillance strategies and targeted risk-reduction measures to improve early detection and patient outcomes.