CYP17 Polymorphisms and Prostate Cancer Outcomes

OBJECTIVE. Cytochrome P450 17 alpha-hydroxylases-C-(17,20)-lyase (CYP17) is a key enzyme involved with the androgen biosynthesis pathway and has recently been targeted for therapy in men with advanced prostate cancer (PCa). However, studies relating prostate cancer outcomes with CYP17 gene variants have conflicting results. In this study we analyzed Single Nucleotide Polymorphisms (SNPs) spanning the CYP17 gene for association with PCa survival. METHODS. The cohort was comprised of Caucasian men, aged 40-64, diagnosed with PCa between 1993 and 1996 in King County, Washington who participated in a population-based case control study. CYP17 SNPs were selected to capture variation across the gene and known regulatory regions. PCa-specific mortality (PCSM) was obtained by linking to the SEER cancer registry. Recurrence/progression of PCa was determined from patient survey data and medical records. Cox proportional hazards regression analysis was used to generate hazard ratios for patient outcomes. RESULTS. Genotypes were available for 598 cases. With a median follow-up of 13.2 years, 44 PCa deaths were observed. Recurrence/progression events were observed in 30% of subjects. No genetic association with disease progression were identified. However, men with the variant A allele in rs10883783 had a 56% risk reduction in PCSM (HR 0.44, 95% CI 0.21-0.98). CONCLUSION. These data suggest that genetic variation in the CYP17 gene in Caucasian men is associated with PCa survival. Prostate 70: 1094-1101, 2010. (C) 2010 Wiley-Liss, Inc.