Uridine 5´-Diphospho-Glucuronosyltransferase Genetic Polymorphisms and Response to Cancer Chemotherapy

Abstract

Pharmacogenetics aims to elucidate how genetic variation affects the efficacy and side effects of drugs, with the ultimate goal of personalizing medicine. Clinical studies of the genetic variation in the uridine 5'-diphosphoglucuronosyltransferase gene have demonstrated how reduced-function allele variants can predict the risk of severe toxicity and help identify cancer patients who could benefit from reduced-dose schedules or alternative chemotherapy. Candidate polymorphisms have also been identified in vitro, although the functional consequences of these variants still need to be tested in the clinical setting. Future approaches in uridine 5'-diphosphoglucuronosyltransferase pharmacogenetics include genetic testing prior to drug treatment, genotype-directed dose-escalation studies, study of genetic variation at the haplotype level and genome-wide studies.