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CYP2D6 polymorphisms and the impact on tamoxifen therapy

✍ Scribed by Jacob N. Beverage; Tristan M. Sissung; Amy M. Sion; Romano Danesi; William D. Figg

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
122 KB
Volume
96
Category
Article
ISSN
0022-3549

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✦ Synopsis

The cytochrome P450 2D6 (CYP2D6) is an enzyme known to metabolize a variety of xenobiotics and drugs. Inter-individual variation in the metabolic capacity of this enzyme has been extensively studied and associations with genotype have been established. Genetic polymorphisms have been grouped as nonfunctional, reduced function, functional, and multiplication alleles phenotypically. Individuals carrying these alleles are presumed to correspond to poor, intermediate, extensive, and ultrarapid metabolizers (UM), respectively. Tamoxifen has been shown to be metabolized by CYP2D6 to the more potent metabolite endoxifen. Poor metabolizers (PM) of tamoxifen have lower levels of endoxifen and poorer clinical outcomes as compared to extensive metabolizers (EM). Here, we will provide an overview of the history and application of CYP2D6 pharmacogenetics, and will discuss the clinical implications of recent developments relating to the involvement of CYP2D6 in tamoxifen treatment. ß 2007

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