Differential associations of SLCO transporters with prostate cancer aggressiveness between African Americans and European Americans

Abstract

Background:Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCOs) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AAs) and European Americans (EAs). Methods:Single nucleotide polymorphisms (SNPs) in 11 SLCO members were selected with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1045 SNPs were genotyped and analyzed in 993 AAs and 1057 EAs from the North Carolina-Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using quantitative RT-PCR, immunohistochemistry, and in situ RNA hybridization in independent sets of prostate cancer cases. Results:Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (P for interaction <0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively. Conclusions:SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs. Impact:The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.