Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study

• Published in: BMC cancer Vol. 24; no. 1; pp. 667 - 7
• Main Authors: Li, Jinshuai, Yang, Zixian, Wang, Tao, Li, Mengqi, Wu, Xiangjian, Fu, Xiaoyan, Yang, Chunfeng, Li, Yangpu, Wang, Ximing, Lan, Zhiming, Li, Minfang, Chen, Sheng
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.05.2024; BioMed Central; BMC
• Subjects: Analysis; Anticholesteremic agents; Apoptosis; Cardiovascular disease; Causal inference; Cervical cancer; Cholesterol; Coenzyme A; Confounding (Statistics); Coronary artery disease; Datasets; Dosage and administration; Drug targeting; Female; Genetic diversity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Heart diseases; HMGCR; Hormone replacement therapy; Humans; Hydroxymethylglutaryl CoA Reductases - genetics; Hydroxymethylglutaryl-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypolipidemic Agents - adverse effects; Hypolipidemic Agents - therapeutic use; Kexin; Kinases; Lipids; Mendelian Randomization Analysis; Methods; Observational studies; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; PCSK9; Polymorphism, Single Nucleotide; Prevention; Proprotein Convertase 9 - genetics; Proprotein convertases; Risk factors; Statins; Therapeutic targets; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; China; PCSK9; HMGCR; MR; Cervical cancer; Ovarian cancer
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-12434-z

The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.