AUTHOR=Liu Luyang , Sheng Chao , Lyu Zhangyan , Dai Hongji , Chen Kexin 

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

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.755834

DOI=10.3389/fnut.2021.755834

ISSN=2296-861X

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 trait on overall and sex-specific RCC risk. Genetic variants of 6 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 (IARC, N =13,230; NCI, N =4,735). 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% confidence interval [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 PCSK9 inhibition was associated with a higher risk of RCC in males (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.