Objective: This study assessed the causal link between lipid traits influenced by lipid-lowering drug targets like HMGCR and PCSK9 and gastric cancer risk. Methods We employed Mendelian randomization with genetic instruments based on genome-wide association study data LDL-C as exposure and gastric cancer as outcome. Analytical approaches included inverse variance weighting as primary method alongside MR-Egger weighted median and mode methods. Sensitivity analyses evaluated result robustness. Results Inverse variance weighting analysis showed HMGCR inhibitor treatment was associated with higher gastric cancer risk OR 1.532 95% CI 1.109-2.118 P 0.010. PCSK9 inhibition similarly elevated risk OR 1.466 95% CI 1.098-1.957 P 0.009. Sensitivity analyses detected no heterogeneity P greater than 0.05. Conclusion In conclusion LDL-C causally affects gastric cancer development. HMGCR and PCSK9 inhibitors appear to raise gastric carcinogenesis risk.
