Warfarin pharmacogenes do not modify the risk association between warfarin use and cancer mortality among men with prostate cancer

Abstract

Abstract Although platelets and thrombosis play a role in cancer progression, anticoagulant drug warfarin has not been independently associated with prostate cancer (PCa) survival. SNPs altering warfarin metabolism may in theory affect the association. We investigated the risk associations by warfarin use stratified by the SNP-profile of CYP2C9 and VKORC1 enzymes known to affect warfarin metabolism. A total of 3,241 men participating in the FinRSPC and 1,436 men with PCa and treated at Tampere University Hospital were genotyped for CYP2C9 SNP rs1057910 and VKORC1 SNP rs9923231 known to affect warfarin metabolism. Cox regression method was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of death overall, cancer death and PCa death after PCa diagnosis. Data on warfaring purchases was obtained from national registry. The SNPs did not modify the risk association between warfarin use and cancer death (HR 1.02, 95% CI 0.77-1.35), PCa progression, clinical features of PCa or the risk of PCa death. Overall risk of death was non-statistically elevated among warfarin users compared to non-users independent of SNP carrier status. SNPs in CYP2C9 and VKORC1 do not modify the association between warfarin use and PCa risk or outcomes among men with PCa. However, use of warfarin is associated with higher overall risk of death independent of metabolic genotype. Our results confirm the previously demonstrated association between anticoagulant use and increased cancer mortality, and suggests the association is not directly caused by warfarin as it is not modified by warfarin metabolism.