Chunxiao Dang,1,* Xiaofeng Wang,2,* Pengfei Liu,1 Jinxing Liu,1 Xiao Yu3 

1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 3Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiao Yu, Affiliated Hospital of Shandong University of Traditional Chinese Medicine Affiliated Hospital, Lixia District, Jinan City, Shandong Province, People’s Republic of China, Tel +8615969675751, Email yux276@126.com Jinxing Liu, Shandong University of Traditional Chinese Medicine, Lixia District, Jinan City, Shandong Province, People’s Republic of China, Tel +8615966696662, Email dcx20151726@163.com

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.

Keywords: lipid-lowering drugs, breast cancer, endometrial cancer, drug-target Mendelian randomization