Abstract

Abstract 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: 795 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 60 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 118 Caucasian men with aHSPC, i.e. those progressing after definitive treatment, 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: Three SNPs in STS (steroid sulfatase gene), and three SNPs in SULT2B1 (sulfotransferase 2B1 gene) were significantly associated with time to CRPC on ADT while controlling for Gleason Score (p < .005). Conclusions: SNPs in STS and SULT2B1 significantly associated with time to CRPC on ADT in aHSPC, and may serve as predictive markers to ADT in this setting. Data are being validated in a larger cohort. Citation Format: Neeraj Agarwal, Tyler Buckley, James Farnham, Shiven B. Patel, Archana Agarwal, Srinivas Tantravahi, Craig Teerlink, Frederick S. Albright, Robert A. Stephenson, Anitha Alex, Lisa Cannon-Albright. Association of single nucleotide polymorphisms (SNPs) in STS and SULT2B1 and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC). [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 39.

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