2001 WHRG Grant Program

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Symposia

Genetic Differences in Tamoxifen Metabolizing Enzymes
in Breast Cancer Patients

Hetal Sheth
School of Medicine, University of Maryland, Baltimore

Tamoxifen (TAM) is a commonly used treatment for women with estrogen responsive (ER+) breast tumors. One study has shown that African-American breast cancer patients have higher mortaility rates than Caucasian breast cancer patients, despite being on similar TAM regimens. One possible explanation for this racial difference in mortality is differential response to treatment. Four major metabolites are formed from the breakdown of tamoxifen, each with a different potency. TAM is generally metabolized by the cytochrome p450 (CYP450) family of enzymes, including CYP1A1. The gene encoding the enzyme contains a polymorphism which has been found to be associated with breast cancer in African-American women. The goal of this study is to test the hypothesis that TAM is metabolized differently in African-American women and Caucasian women, and that racial differences in TAM metabolism are due, in part, to genetic polymorphisms in CYP1A1. In the proposed study, 60 African-American and 60 Caucasian postmenopausal women with breast cancer will be recruited from a single clinical practice. Polymorphic status in these breast cancer patients will be determined by using PCR methods and restriction enzyme digest. Statistical methods will be used to determine possible associations between polymorphic status and specific side effects. In addition, the genetic polymorphism will be evaluated for its correlation to the amounts of specific TAM metabolites. Any association found between CYP1A1 polymorphic status and/or metabolites could provide a basis for investigating the clinical utility of this polymorphism as a possible biological marker for differential tamoxifen metabolism in women with breast cancer.