Genetically Proxied Therapeutic Effect of Lipid-Lowering Drugs Use, Breast Cancer, and Endometrial Cancer's Risk: A Drug Target-Based Mendelian Randomization Study.
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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.
期刊介绍：
International Journal of Women''s Health is an international, peer-reviewed, open access, online journal. Publishing original research, reports, editorials, reviews and commentaries on all aspects of women''s healthcare including gynecology, obstetrics, and breast cancer. Subject areas include: Chronic conditions including cancers of various organs specific and not specific to women Migraine, headaches, arthritis, osteoporosis Endocrine and autoimmune syndromes - asthma, multiple sclerosis, lupus, diabetes Sexual and reproductive health including fertility patterns and emerging technologies to address infertility Infectious disease with chronic sequelae including HIV/AIDS, HPV, PID, and other STDs Psychological and psychosocial conditions - depression across the life span, substance abuse, domestic violence Health maintenance among aging females - factors affecting the quality of life including physical, social and mental issues Avenues for health promotion and disease prevention across the life span Male vs female incidence comparisons for conditions that affect both genders.
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