Association of SLCO transport genes with intraprostatic abiraterone (ABI) levels and pathologic outcomes in men with high-risk localized prostate cancer (PCa).

Abstract

5013 Background: Germline variation in solute carrier organic anion (SLCO) transport genes influences cellular uptake of steroids and has been associated with PCa outcomes. We hypothesized that due to its steroidal structure, ABI may undergo SLCO-mediated transport, and that germline variation in SLCO genes may influence intracellular ABI levels and pathologic outcomes in men with PCa. Methods: We measured ABI levels in prostatectomy tissue from 58 men with localized PCa treated with 6 months of castration plus ABI prior to radical prostatectomy (RP). Buffy coat DNA was genotyped for13 SNPs (minimum allele frequency > 0.07) in 6 SLCO genes using TaqMan SNP assays. Transcript expression of SLCO genes was evaluated by qRT-PCR in microdissected tumor samples from a subset of patients. Results: SNPs in SLCO1B3 (rs4149177, p = 0.07) and SLCO2B1 (rs12422149, p = 0.0004; rs949069, p = 0.008; rs1789693, p = 0.01) were associated with significant differences in mean tissue ABI levels at RP. Contingency analysis sh...