Re: Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4

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Abstract
In the recent study on a new variant of the cytochrome P450 3A4 (CYP3A4) gene by Rebbeck et al. ( 1 ), the authors did not provide data that demonstrate an alteration of CYP3A4 function as a consequence of the polymorphism. They suggested that the variant allele might alter disposition of the androgenic substrates of CYP3A4 as a result of decreased enzymatic activity. Worse clinical presentation of prostate cancer ( 1 ) and a decreased risk for treatment-related leukemia ( 2 ) were reported to be associated with the variant allele, the former probably due to increased bioavailability of testosterone and the latter probably due to reduced production of leukemogenic metabolites of anticancer drugs. Thus, we investigated the possible relationship between CYP3A4 genotypes and nifedipine oxidation activity, a prototype reaction of the encoded enzyme, by use of a human liver microsome system in vitro.
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