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Potential Role of UGT Pharmacogenetics in Cancer Treatment and Prevention

Focus on Tamoxifen

Authors


  • These studies were supported by Public Health Service grant R01-DE13158 (Lazarus) from the National Institutes of Health, and a formula grant under the Pennsylvania Department of Health's Health Research Formula Funding Program, State of PA, Act 2001-77 – part of the PA Tobacco Settlement Legislation (Lazarus).

Address for correspondence: Philip Lazarus, Ph.D., Penn State Cancer Institute, Penn State University College of Medicine, Rm. C3739D, MC-H069, 500 University Drive, Hershey, Pennsylvania 17033. Fax: +717-531-0480. plazarus@psu.edu

Abstract

Tamoxifen (TAM) is a selective estrogen receptor modulator that is widely used in the prevention and treatment of estrogen receptor-positive (ER+) breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30–50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and occurrence of contralateral breast cancer. However, in patients treated with TAM there is substantial interindividual variability in the development of resistance to TAM therapy, and in the incidence of TAM-induced adverse events, including deep vein thrombosis, hot flashes, and the development of endometrial cancer. This article will focus on the UDP glucuronosyltransferases, a family of metabolizing enzymes that are responsible for the deactivation and clearance of TAM and TAM metabolites, and how interindividual differences in these enzymes may play a role in patient response to TAM.

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