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Pharmacogenetics of Estrogen Metabolism and Transport in Relation to Cancer

[ Vol. 4 , Issue. 6 ]


Nehal J. Lakhani, Jurgen Venitz, William D. Figg and Alex Sparreboom   Pages 505 - 513 ( 9 )


Exposure to estrogens has been long associated with the genesis of human malignancies, including breast, ovarian, and endometrial cancer. A variety of phase I and II enzymes are involved in the metabolic activation and deactivation of estrogens, including cytochrome P450 isoforms, estrone sulfatase, sulfotransferases, catechol-o-methyltransferase, and uridine-5-diphosphate glucuronosyltransferase. In addition, at least one ATP-binding cassette gene (i.e., ABCG2) is involved in estrogen transport. Variability in the expression levels of these proteins may have important consequences for an individuals susceptibility to certain malignancies. Naturally occurring variants in the genes involved in estrogen exposure levels have been identified that might affect protein function and expression. This review focuses on recent advances in the pharmacogenetics of these proteins, and discusses potential clinical ramifications of these genetic variants.


estrogen, metabolism, transport, cancer, pharmacogenetics


Clinical Pharmacology Research Core, Center for Cancer Research, National Cancer Institute,National Institutes of Health, Bldg 10, Rm 5A01, 9000 Rockville Pike, Bethesda, MD 20892, USA.

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