Abstract
BACKGROUND: Observational studies have investigated the association between lipid-lowering drugs and breast cancer (BC) and endometrial cancer (EC), but some controversy remains. OBJECTIVE: This paper aims to explore the causal relationship between genetic proxies for lipid-lowering drugs and breast and endometrial cancers using drug-target Mendelian randomization (MR). METHODS: Analyses were mainly performed using inverse variance weighted (IVW), heterogeneity and horizontal pleiotropy tests, and sensitivity analysis to assess the robustness of the results and causal relationship. RESULTS: HMGCR, APOB, and NPC1L1 increased the risk of breast cancer, LPL increased the risk of endometrial cancer, and APOC3 decreased the risk of breast and endometrial cancer. No heterogeneity or horizontal pleiotropy was detected, and nor was there any evidence of an association between other lipid-lowering drugs and breast and endometrial cancer. CONCLUSION: Our study demonstrated genetically that HMGCR inhibition, APOB inhibition, and NPC1L1 inhibition decrease the risk of breast cancer, LPL agonist increases the risk of endometrial cancer, and APOC3 inhibition decreases the risk of breast cancer and endometrial cancer, and these findings provide genetic insights into the potential risks of lipid-lowering drug therapy.