SNP genotypes in CYP2C9 and VKORC1 genes do not affect prostate cancer or cancer mortality among warfarin users in Finnish prostate cancer patients

Abstract

The coagulation cascade is thought to contribute to cancer progression. Although in vitro studies suggest that anticoagulants, such as warfarin, might reduce cancer progression, epidemiological data indicate that warfarin users may have a higher risk of cancer mortality. However, single nucleotide polymorphisms (SNPs) that influence warfarin dosing might affect this association. We investigated the risk associations between warfarin use and prostate cancer (PCa) survival, considering the SNP genotypes of CYP2C9 and VKORC1, which are known to impact both warfarin pharmacokinetics and pharmacodynamics, resulting in lower warfarin dose requirement. We genotyped 2,246 Finnish men with PCa from two different cohorts for SNPs rs1057910, rs1799853, and rs9923231. Genotyping was done using a custom Illumina iSelect genotyping array (iCOGs). Using Cox regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for the risk of overall death, cancer deaths overall, and PCa-specific death after PCa diagnosis based on SNP genotypes. Data on warfarin purchases was obtained from a national registry. Our findings revealed that the SNPs did not alter the risk of cancer or PCa death in either cohort, nor did they modify the risk among warfarin users. However, overall mortality was higher among warfarin users compared to non-users, particularly in carriers of all three SNPs. Even though the increased mortality is likely due to confounding by indication, warfarin use may increase overall mortality especially in men with lower warfarin dose requirements due to SNP carrier status. However, we need further studies with larger populations to confirm these findings.