Asp85Tyr polymorphism in the UDP-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer

Purpose: An amino acid changing polymorphism in the UDP-glucuronosyltransferase (UGT) 2B15 gene has been described at codon 85 (aspartate>tyrosine). The UGT2B15^85Asp allele exhibits 2-fold decreased activity for dihydrotestosterone, which was suggested to be associated with the risk of prostate cancer based on in vitro functional analysis. We determined whether this polymorphism can be used to predict individual susceptibility to prostate cancer. Materials and Methods: UGT2B15 expression was determined by reverse transcription-polymerase chain reaction of normal prostate tissues. Prevalence of the UGT2B15 Asp85Tyr polymorphism was compared between cases and controls by allele specific polymerase chain reaction analysis using genomic DNA isolated from 155 incident white patients with primary prostate cancer and 155 individually age matched (±5 years) white controls. Results: UGT2B 15 mRNA was detected in all prostate tissues tested. A significant association was found between UGT2B15 genotypes and prostate cancer risk. A significantly increased risk of prostate cancer was observed in subjects with the homozygous UGT2B15^85Asp/Asp genotype (OR 2.7, 95% CI 1.1 to 6.6). Conclusions: These results suggest that the UGT2B15 enzyme may have a role in the metabolism of dihydrotestosterone in prostate tissue and UGT2B15 Asp85Tyr polymorphism is associated with prostate cancer risk.