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

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CYP3A4 is a member of the cytochrome P450 supergene family that mediates the metabolism of numerous compounds involved in human carcinogenesis, including steroid hormones such as testosterone. Recently, a variant in the 5′ regulatory region of CYP3A4 (CYP3A4-V) was reported to confer higher stage prostate tumors compared with homozygous wild-type CYP3A4 (CYP3A4-W) in both Caucasians and African-Americans (1,2). To date, these associations have not been supported by data that address the functional significance of this polymorphism.

Westlind et al. (3) recently reported that CYP3A4-V had no effect on testosterone 6β-hydroxylation (T6βH). However, this inference was made without any formal statistical analysis. By using the raw data provided in that paper, genotype-specific mean values of T6βH were computed. The mean T6βH in CYP3A4-W homozygotes (n = 36) was 1660.6 pmol/mg per minute, whereas the mean T6βH in carriers of a CYP3A4-V allele (n = 3) was 4850.0 pmol/mg per minute. This difference was highly statistically significant by analysis of variance with F_1,37 = 13.85 (P = .0007) and by Kruskal-Wallis analysis of variance by ranks with χ²₁ = 5.63 (P = .02). Thus, despite the small sample size, these data support the inference that CYP3A4-V is associated with altered testosterone metabolism.