A polymorphism in the UDP-Glucuronosyltransferase 2B15 gene (D85Y) is not associated with prostate cancer risk.

Introduction UGT, a family of Phase II detoxification enzymes, catalyzes the transfer of the glucuronyl group from uridine diphosphogluronic acid to many substrates, including steroid hormones (1). Glucuronidation, an irreversible step in the pathway of steroid metabolism, converts steroids into polar, water soluble derivatives and may alter the levels of active androgens in steroid target tissues, such as the prostate. UGT2B15, a member of the UGT2B subfamily, is expressed in the liver as well as in several extrahepatic tissues, including the prostate, and is responsible for the glucuronidation of androgens (2). In the human UGT2B15 gene, a guanine-to-thymine single bp polymorphism has been identified that results in an amino acid change from aspartate (D) to tyrosine (Y) at position 85 (2). UGT2B15(D) and UGT2B15(Y) have similar substrate specificities. However, UGT2B15(Y) has a 2-fold higher Vmax than UGT2B15(D ) for C19 steroids, such as 5 -androstane-3 ,17 -diol and dihydrotestosterone (3). Because UGT2B enzymes play an important role in steroid metabolism and excretion, we investigated the association of the UGT2B15(DY) polymorphism and prostate cancer in a case control study of 190 patients with histologically verified, previously untreated prostate cancer and 190 age-matched control patients with BPH.