TY - JOUR
T1 - Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer
AU - Nagar, S.
AU - Remmel, R. P.
PY - 2006/3/13
Y1 - 2006/3/13
N2 - The uridine diphosphoglucuronosyltransferases (UGTs) belong to a superfamily of enzymes that catalyse the glucuronidation of numerous endobiotics and xenobiotics. Several human hepatic and extrahepatic UGT isozymes have been characterized with respect to their substrate specificity, tissue expression and gene structure. Genetic polymorphisms have been identified for almost all the UGT family members. A wide variety of anticancer drugs, dietary chemopreventives and carcinogens are known to be conjugated by members of both UGT1A and UGT2B subfamilies. This review examines in detail each UGT isozyme known to be associated with cancer and carcinogenesis. The cancer-related substrates for several UGTs are summarized, and the functionally relevant genetic polymorphisms of UGTs are reviewed. A number of genotype-phenotype association studies have been carried out to characterize the role of UGT pharmacogenetics in several types of cancer, and these examples are discussed here. In summary, this review focuses on the role of the human UGT genetic polymorphisms in carcinogenesis, chemoprevention and cancer risk.
AB - The uridine diphosphoglucuronosyltransferases (UGTs) belong to a superfamily of enzymes that catalyse the glucuronidation of numerous endobiotics and xenobiotics. Several human hepatic and extrahepatic UGT isozymes have been characterized with respect to their substrate specificity, tissue expression and gene structure. Genetic polymorphisms have been identified for almost all the UGT family members. A wide variety of anticancer drugs, dietary chemopreventives and carcinogens are known to be conjugated by members of both UGT1A and UGT2B subfamilies. This review examines in detail each UGT isozyme known to be associated with cancer and carcinogenesis. The cancer-related substrates for several UGTs are summarized, and the functionally relevant genetic polymorphisms of UGTs are reviewed. A number of genotype-phenotype association studies have been carried out to characterize the role of UGT pharmacogenetics in several types of cancer, and these examples are discussed here. In summary, this review focuses on the role of the human UGT genetic polymorphisms in carcinogenesis, chemoprevention and cancer risk.
KW - Drug metabolism
KW - Genetic polymorphisms
KW - Uridine diphosphoglucuronosyltransferase
UR - http://www.scopus.com/inward/record.url?scp=33645120407&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645120407&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1209375
DO - 10.1038/sj.onc.1209375
M3 - Review article
C2 - 16550166
AN - SCOPUS:33645120407
SN - 0950-9232
VL - 25
SP - 1659
EP - 1672
JO - Oncogene
JF - Oncogene
IS - 11
ER -
