Clinical implications of a prostate cancer risk SNP profile in two treatment cohorts.

Abstract

e16000 Background: Prostate cancer (PCa) has a heritable risk and genome-wide association studies (GWAS) have so far identified 76 single nucleotide polymorphisms (SNPs) associated with PCa risk. Currently these SNPs have only been evaluated against overall PCa risk and several disease parameters. Their clinical utility remains undefined. We explore the potential prognostic role of the risk SNP profile in 2 PCa cohorts; Active Surveillance (AS) and androgen deprivation therapy (ADT). Methods: PCa patients at the Royal Marsden Hospital who consented for DNA analyses were eligible. 2 separate cohorts were identified; those undergoing AS and those receiving ADT. The risk SNPs were genotyped using Sequenom or Fluidigm platforms. The cumulative SNP risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies (log-additive model). For the AS group, the risk scores were analysed against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. For the ADT group, the risk scores were assessed against time to relapse, defined by either biochemical relapse or evidence of progression on imaging. Results: In the AS group, 391 patients’ DNA were studied. 31% of those have since undergone treatment and 30% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between the risk scores and biopsy upgrade or time to treatment (p>0.05). When analysing differences in outcomes between the higher and lower risk groups (top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p>0.05). In the ADT group, 567 patients’ DNA were studied. The mean duration of response was 30 months. No significant associations were found when risk scores were analysed as a continuous variable against time to relapse on ADT, or when analysing difference between the top and bottom 25% of the risk distribution (p>0.05). Conclusions: PCa SNP risk scores have not been shown to be prognostic factors in either AS or ADT. This is the first study analysing the potential prognostic role of the latest GWAS risk SNPs in PCa treatment cohorts.