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

Paul Carter, Mathew Vithayathil, Siddhartha Kar, Rahul Potluri, Amy M Mason, Susanna C Larsson, Stephen Burgess*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
15 Downloads (Pure)

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.
Original languageEnglish
Article numbere57191
Number of pages17
JournaleLife
Volume9
DOIs
Publication statusPublished - 13 Oct 2020

Keywords

  • Research Article
  • Cell Biology
  • Chromosomes and Gene Expression
  • genetic epidemiology
  • statins
  • lipids
  • causal inference
  • Mendelian randomization
  • cholesterol

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