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 2 = 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 2 = 0%), respectively. This meta-analysis suggests that BRCA1/2 mutation carriers have a higher risk of developing gastric cancer. Stomach cancer is one of the most common and deadly cancers worldwide. While most cases happen by chance, a small number are linked to inherited genetic changes. Two important genes, BRCA1 and BRCA2, are known for increasing the risk of breast and ovarian cancer, especially in women. However, recent studies suggest that changes in these genes might also raise the risk of stomach cancer. In this study, we reviewed and combined data from multiple previous studies to better understand the link between BRCA1/2 mutations and stomach cancer. We found that people with these mutations are more likely to develop the disease. This risk was especially clear in those with BRCA2 mutations. We also found that stomach cancer patients who carry these mutations may be more common than expected. Our findings highlight the importance of genetic testing in people with a family history of stomach cancer, even if they have not had breast or ovarian cancer. Men, who are often less likely to be tested for BRCA mutations, may also benefit from earlier screening. This research may help doctors identify high-risk individuals and offer personalized strategies for prevention, early detection, and treatment.