Association of single nucleotide polymorphism in four genes and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC).

Abstract

224 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict time to response to androgen deprivation therapy (ADT) in aHSPC, serve as prognostic and predictive biomarkers, and guide towards more individualized upfront therapy. Methods: 706 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 59 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to onset of castration resistance prostate cancer (CRPC) in 171 Caucasian men with aHSPC, i.e. those progressing after definitive treatment (biochemical recurrence alone, or onset of metastatic disease), undergoing treatment with ADT. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Five SNPs in four genes showed evidence of association with time to CRPC on ADT while controlling for Gleason Score (p < .0002) (Table). Each of these genes had other nearby SNPs with at least nominal (p < 0.05) significance and so, don’t appear to be false positives. Conclusions: Although none of these SNPs exceeded a strict Bonferoni multiple testing correction (p < 0.00007), that threshold is almost certainly conservative as the SNPs and tests are correlated. These results are being validated in a larger cohort and may serve as predictive markers to ADT in this setting. [Table: see text]