UGT pharmacogenomics: implications for cancer risk and cancer therapeutics

Abstract

UDP-glucuronosyltransferases (UGTs) belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds including bilirubin, hormones, various drugs as well as environmental carcinogens. Glucuronidation predominantly serves as a pathway for elimination of the different glucuronidated compounds. Seventeen human UGT transcripts have been identified thus far, and the UGT proteins are differentially expressed in a wide-range of human tissues. Genetic variants have been identified in coding and non-coding sequences of several UGT genes, and similar observations should be anticipated for all UGTs. As glucuronidation plays a critical part in the inactivation or elimination of countless substrates, genetic variants in this enzyme family that lead to altered expression or activity of UGTs are likely to have some physiologic and pharmacological consequences. This article focuses on the potential impact of various UGTs or their variants on cancer risk and cancer therapeutics.