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

Abstract

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. 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. 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. 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.