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

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Abstract
The variable expression and activity of CYP3A isozymes observed in the population has been discussed as a factor that affects both response to therapies and the individual cancer predisposition. The CYP3A4-V gene variant in the 5`-regulatory region of the CYP3A4 gene (herein referred to as CYP3A4*1B) was associated with high-grade prostate cancer (1) and with a reduced risk for treatment-related leukemia (2). It has been postulated that CYP3A4*1B might reduce CYP3A4 expression and thereby decrease both steroid metabolism in the prostate and production of DNA-damaging chemotherapeutic metabolites (1,2). However, although the single nucleotide polymorphism disrupts a putative regulatory element in the CYP3A4 promoter, several studies did not detect any substantial effect of CYP3A4*1B on CYP3A4 expression or activity [(3) and references therein].
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