Effects of agents acting on the renin-angiotensin system on the incidence of gastric cancer: A two-sample Mendelian randomization study

The purpose of this study was to investigate whether there is a causal relationship between agents acting on the renin-angiotensin system (RAS) and gastric cancer (GC) using Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis using publicly available Genome-Wide Association Study data. The inverse-variance weighted (IVW) method served as the primary analytical approach, while complementary methods, including weighted median, weighted mode, and MR-Egger regression, were also applied. Sensitivity analyses included MR-Egger regression to test for pleiotropy and the application of Cochran Q statistics via IVW and MR-Egger regression to assess heterogeneity. MR analysis demonstrated a significant inverse association between agents acting on the RAS and GC risk (IVW odds ratio = 0.797; 95% confidence interval: 0.723-0.879; P < .001). Sensitivity analyses showed no evidence of heterogeneity or horizontal pleiotropy, supporting the robustness and validity of the findings. These results suggest a potential causal relationship, highlighting the protective role of these agents in reducing GC risk. This study provides genetic evidence supporting a potential causal relationship between agents acting on the RAS and reduced GC risk, which requires further clinical validation.