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Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Carter, Paul 
Vithayathil, Mathew 
Kar, Siddhartha 
Potluri, Rahul 
Mason, Amy M 

Abstract

Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. Here we assess the potential effect of statin therapy on cancer risk using evidence from human genetics. We obtained associations of lipid-related genetic variants with the risk of overall and 22 site-specific cancers for 367,703 individuals in the UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (odds ratio [OR] per one standard deviation decrease in low-density lipoprotein [LDL] cholesterol 0.76, 95% confidence interval [CI] 0.65-0.88, p=0.0003) but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically predicted LDL-cholesterol was not associated with overall cancer risk (OR per standard deviation increase 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk but other lipid-lowering treatments do not. This suggests that statins reduce cancer risk through a cholesterol independent pathway.

Description

Keywords

Mendelian randomization, causal inference, cell biology, cholesterol, chromosomes, gene expression, genetic epidemiology, human, lipids, statins, Biological Specimen Banks, Genetic Variation, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mendelian Randomization Analysis, Neoplasms, Prevalence, Risk Factors, United Kingdom

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd

Rights

All rights reserved
Sponsorship
Wellcome Trust (204623/Z/16/Z)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
Medical Research Council (MC_UU_00002/7)