Bidirectional Mendelian randomization analysis of hypertension, coronary artery disease, and gastric cancer with supplementary clinical data

Background: The relationship between gastric cancer and cardiovascular traits, including hypertension and coronary artery disease (CAD), remains incompletely understood. Observational studies are prone to confounding and reverse causation, and genetic evidence may help clarify the nature of these associations. Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) summary statistics to investigate the relationships between gastric cancer, hypertension, and CAD. Multiple MR methods and sensitivity analyses were applied to assess robustness. To provide supplementary clinical context, we additionally conducted a small retrospective clinical analysis of 45 individuals, including gastric cancer cases and non-cancer controls, using logistic regression adjusted for age and sex. Results: MR analyses showed no evidence that genetic liability to gastric cancer was associated with the risk of hypertension or CAD. In contrast, genetic predisposition to hypertension was inversely associated with gastric cancer risk. These findings were consistent across sensitivity analyses. In the retrospective cohort, hypertension was not significantly associated with gastric cancer risk. Conclusions: This study provides genetic evidence supporting an inverse association between hypertension liability and gastric cancer risk. However, the supplementary retrospective clinical analysis was limited by its small sample size and did not provide independent validation of the MR findings. Larger observational studies are needed. Further studies are warranted to clarify the underlying biological mechanisms.