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. 2024 May 31;24(1):667.
doi: 10.1186/s12885-024-12434-z.

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

Jinshuai Li  1   2 , Zixian Yang  3 , Tao Wang  1   2 , Mengqi Li  4 , Xiangjian Wu  1   2 , Xiaoyan Fu  1   2 , Chunfeng Yang  1   2 , Yangpu Li  1   2 , Ximing Wang  1   2 , Zhiming Lan  1   2 , Minfang Li  1   2 , Sheng Chen  5   6
Affiliations

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

Jinshuai Li et al. BMC Cancer. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cervical cancer; HMGCR; MR; Ovarian cancer; PCSK9.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study overview and design of MR analysis of drug targets
Fig. 2
Fig. 2
Effects of HMGCR and PCSK9 inhibitors on CHD, OC, and CC
Fig. 3
Fig. 3
Repeated analyses were conducted to assess the effects of HMGCR and PCSK9 inhibitors on CHD, OC, and CC
See this image and copyright information in PMC

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