The association between statin use, genetic variation, and prostate cancer risk.

Abstract

Background: The association between statin medication use and prostate cancer remains inconclusive. Evidence shows that genetic variation modifies lipid-lowering efficacy of statins, however, there are limited data on the pharmacogenomics of statins in prostate cancer chemoprevention.

Methods: Clinical and germline data were extracted from the prostate biopsy database at the University Health Network, Toronto, Canada (1996-2014). A genome-wide association study (GWAS) and a custom array of 54 single nucleotide polymorphisms (SNPs) related to statin metabolism were performed. Using a case-control design, we examined the associations between statin use and overall and high-grade (Grade Group ≥2) prostate cancer risk. A case-only design was employed to explore interactions between candidate/GWAS SNPs and the statin-cancer association.

Results: Among 3481 patients, 1104 (32%) were using statins at biopsy. Statin users were older and had higher body mass index, greater number of positive cores, and higher Gleason scores. In total, 2061 participants (59%) were diagnosed with prostate cancer, with 922 cases (45%) classified as high-grade. When adjusted for baseline characteristics, the use of statins was not associated with decreased risk of overall or high-grade prostate cancer. Two unique SNPs implicated in statin metabolism showed significant interaction with the statin-cancer association. In particular, statin users harboring the GG genotype (n = 668; 24%) of rs10276036 had significantly lower prostate cancer risk (HR 0.71, 95% CI 051-1.00). However, none of the SNPs achieved genome-wide significance.

Conclusions: In our study, statin use was not associated with either prostate cancer or high-grade prostate cancer risk. While one candidate SNP that influences statin metabolism may be associated with a lower cancer risk among statin users and thus warrants further study, neither this nor any other SNPs achieved genome-wide significance. Thus, our findings do not add evidence in support of a prostate cancer chemopreventive role for statins.