Modulation of UDP Glucuronosyltransferase 2B15 and 2B17 and prostate cancer risk : current perspectives

Thind, Jasmine, Jenkinson, Carl, Naughton, Declan and Petroczi, Andrea (2013) Modulation of UDP Glucuronosyltransferase 2B15 and 2B17 and prostate cancer risk : current perspectives. Advances in Cancer: Research & Treatment, 2013(ID 81212),


UDP glucuronosyltransferases (UGTs) are a family of enzymes that glucuronidate a variety of exogenous and endogenous compounds, including androgens; which makes them more hydrophilic, changes biological activity, and aids biological excretion. UGT2B17 has been identified as the major enzyme for testosterone glucuronidation, where UGT2B15 has been suggested to play a minor role. A deletion polymorphism in the UGT2B17 gene and an amino acid change in the UGT2B15 gene at codon 85 (aspartate>tyrosine) has been described where the resulting reduced rate of glucuronidation was implicated in the increased risk of prostate cancer. This review aims to analyse the impact that UGT2B15 and UGT2B17 genetic polymorphisms have on the risk of prostate cancer, through the use of studies previously conducted assessing the level of expression of each independent UGT2B enzyme, whereby ethnicity was taken into account. Positive and negative outcomes of clinical studies have been outlined for both UGT2B15 and UGT2B17, where conflicting evidence has led to inconclusive results for determining the consequence of UGT2B enzymes in prostate cancer risk. Additionally, inhibitors of testosterone glucuronidation such as non-steroidal, antiinflammatory drugs (diclofenac and ibuprofen), tea and red wine extracts have been identified to potentially affect the level of circulating testosterone by inhibiting UGT2B enzymes, thus potentially exacerbating prostate cancer risk. Future trials would involve a wider examination of other food substances and pharmaceuticals that can be attributed to the inhibition of UGT2B enzymes.

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