Gastric cancer risk and BRCA1/2 mutations: a systematic review and meta-analysis

Gastric cancer is an aggressive and heterogeneous disease, primarily sporadic, with only 1-3% of cases being hereditary. However, gastric cancer is a component of several hereditary cancer syndromes. The BRCA1 and BRCA2 genes encode key DNA repair proteins involved in homologous recombination. Studies suggest a significantly increased risk of gastric cancer in first-degree relatives of BRCA1/2 mutation carriers. We systematically searched PubMed, Scopus, and Web of Science for relevant studies. Risk ratios (RRs) with 95% confidence intervals (CIs) were computed using DerSimonian and Laird random-effect models. Heterogeneity was assessed via I2 statistics. Statistical analyses were performed using R (version 4.2.3). Fourteen studies with 160,551 patients were included, of whom 25,934 had BRCA1/2 mutations (BRCA1: 14322; BRCA2: 11612). BRCA1 and BRCA2 mutations were significantly associated with increased gastric cancer risk (RR 2.30; 95% CI: 1.33-3.97; p = 0.003; I2 = 82% and RR 2.45; 95% CI: 1.82-3.28; p < 0.001; I2 = 25%). Among the gastric cancer patients, BRCA1 and BRCA2 mutations were associated with RRs of 3.02 (p = 0.101; I2 = 65%) and 4.86 (p < 0.001; I2 = 0%), respectively. This meta-analysis suggests that BRCA1/2 mutation carriers have a higher risk of developing gastric cancer.