An allele-specific polymerase chain reaction method for the determination of the D85Y polymorphism in the human UDP-glucuronosyltransferase 2B15 genein a case-control study of prostate cancer

Background: UDP-glucuronosyltransferase 2B15 (UGT2B15) catalyzes the inacti vation of dihydrotestosterone (DHT) by forming the DHT-glucuronide and is e xpressed in normal and hyperplastic prostate tissue. Alterations in the act ivity of this enzyme could be a major contributing factor to the bioavailab ility of androgens in target tissue such as the prostate. Methods: A polymorphism (D-85 to Y-85) has been identified in the UGT2B15 g ene(1) that results in a 50% reduction in enzyme activity. Previously, dete ction of the polymorphic nucleotide has required direct sequencing. We have developed and validated an allele-specific polymerase chain reaction (PCR) assay to identify the polymorphic base pair in the UGT2B15 gene. This assa y was used to examine the distribution of the UGT2B15 polymorphism in a sma ll case-control group (64 cases and 64 controls) from a prostate cancer stu dy. Results: The results of this analysis show that prostate cancer patients we re significantly more likely to be homozygous for the lower activity D85 UG T2B15 allele than control individuals (41% versus 19%, respectively, odds r atio = 3.0 (95% confidence intervals 1,3-6.5)), Conclusions: These results suggest that individuals who are homozygous for the lower activity allele may be at increased risk for developing prostate cancer.