Risk of gastric cancer among people with BRCA pathogenic gene variants: A systematic review and meta-analysis.

Abstract

e16153 Background: Patients with BRCA pathogenic gene variants (PGVs) have an increased risk for breast, ovarian, pancreatic, and prostate cancer, with emerging evidence suggesting an association with gastric cancer. It is critical to evaluate the strength of this association to guide optimal cancer risk-management recommendations. Methods: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO no.: CRD42024551721). Systematic searches in Ovid MEDLINE, Embase, and Cochrane CENTRAL were conducted in May 2024 to identify studies evaluating the association of gastric cancer with germline BRCA PGV status. Data from eligible studies were meta-analyzed. Results: Nineteen studies were included. Among 13,688 gastric cancer patients, the pooled prevalence of BRCA1/2 PGVs was 1.8% (95% CI 1.2% - 2.5%), with the pooled prevalence of BRCA1 PGVs being 1.5% (95% CI 0.7% - 2.2%), and that of BRCA2 PGVs being 0.8% (95% CI 0.4% - 1.3%). Among 10,683 gastric cancer patients compared to 42,184 controls, the pooled OR of having a BRCA1 PGV was 2.92 (95% CI 0.98 – 0.68); there were insufficient data to meta-analyze the pooled OR for BRCA2 PGVs. Conclusions: This systematic review and meta-analysis demonstrate that nearly 2% of patients with gastric cancer have germline PGVs in BRCA1/2. We found extremely limited data comparing the rate of germline BRCA PGVs in gastric cancer patients compared to control populations, and as such a conclusive meta-analysis for this was not possible. Given the pooled prevalence of germline BRCA PGVs among gastric cancer patients in our results is 3-4 times higher the general population frequency of these PGVs, it is critical to further investigate the risk of gastric cancer among BRCA PGV carriers with high-quality prospective studies to inform cancer risk management among these patients.