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Association Between Genetically Proxied Lipid-Lowering Drug Targets and Renal Cell Carcinoma: A Mendelian Randomization Study

Authors :
Luyang Liu
Chao Sheng
Zhangyan Lyu
Hongji Dai
Kexin Chen
Source :
Frontiers in Nutrition, Vol 8 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Observational studies suggested inconsistent associations between lipid-lowering drugs, such as statins, and renal cell carcinoma (RCC) risk. In a two-sample Mendelian randomization (MR) framework, we assessed the causal influence of lipid-lowering agents and circulating lipid traits on overall and sex-specific RCC risk. Genetic variants of six drug-target genes were selected to proxy the effects of low-density lipoprotein cholesterol (LDL-C) lowering therapies. Instrumental variables for circulating lipid traits were constructed from two large genome-wide association studies. We used endpoints for RCC from summary statistics of two studies [International Agency for Research on Cancer [IARC], N = 13,230; National Cancer Institute [NCI], N = 4,735]. The robustness of results was assessed through conventional MR sensitivity analyses. Overall, there was no significant association between genetically proxied HMG-CoA reductase (HMGCR) inhibition and RCC risk [Odds ratio [OR] = 1.42, 95% CI, 0.29–6.99]. In the sex-stratified analysis, we observed a positive association for genetically proxied drug targets with RCC risk. Specifically, genetically proxied proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition was associated with a higher risk of RCC in men [OR = 2.20 [95% CI, 1.24–3.89]], and the difference by sex was moderate. This study suggested genetically proxied inhibition of HMGCR was not associated with RCC risk, while genetically proxied PCSK9 inhibition might be associated with a higher risk of RCC in male.

Details

Language :
English
ISSN :
2296861X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Nutrition
Publication Type :
Academic Journal
Accession number :
edsdoj.6ed1062f4404eab8fcae4884b37eb4a
Document Type :
article
Full Text :
https://doi.org/10.3389/fnut.2021.755834