title: Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.
abstract: Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field.
authors.affiliation: a Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer , Flinders University School of Medicine, Flinders Medical Centre , Bedford Park, SA , Australia.
authors.forename: Dong Gui
authors.initials: DG
authors.lastname: Hu
authors.affiliation: a Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer , Flinders University School of Medicine, Flinders Medical Centre , Bedford Park, SA , Australia.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Mackenzie
authors.affiliation: a Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer , Flinders University School of Medicine, Flinders Medical Centre , Bedford Park, SA , Australia.
authors.forename: Ross A
authors.initials: RA
authors.lastname: McKinnon
authors.affiliation: a Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer , Flinders University School of Medicine, Flinders Medical Centre , Bedford Park, SA , Australia.
authors.forename: Robyn
authors.initials: R
authors.lastname: Meech
mesh_terms: D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D014453:Glucuronosyltransferase
keywords: UDP-glucuronosyltransferase; cancer risk; case-control study; pharmacogenetics; polymorphism; single nucleotide polymorphism