Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial
Cindy H. Chau, Douglas K. Price, Cathee Till, Phyllis J. Goodman, Xiaohong Chen, Robin J. Leach, Teresa L. Johnson-Pais, Ann Wu Hsing, Ashraful M. Hoque, Catherine M. Tangen, et al.
PLoS ONE2015
Summary (paraphrased)
Using a nested case-control design inside the Prostate Cancer Prevention Trial, the authors measured serum finasteride by validated LC-MS and tested 27 SNPs in finasteride target and metabolism genes for association with drug concentrations. Five SNPs in CYP3A4 (rs2242480, rs4646437, rs4986910) and CYP3A5 (rs776746, rs15524) were associated with finasteride levels: variant alleles at three SNPs raised mean concentrations more than 1.5-fold, while homozygous variants at the other two halved them. No SRD5A2 or SRD5A3 variants associated with concentrations, and finasteride concentration itself showed no concentration-dependent association with prostate cancer risk. The authors conclude CYP3A4/5 genetics substantially modify systemic finasteride exposure.
Why it’s in the systems review
This is the only human study found that directly ties common genetic variants to finasteride blood levels — the exposure variable at the very start of any PFS causal chain — with effect sizes large enough to matter (halving to 1.5x-plus). It converts "CYP3A4 metabolizes finasteride" from textbook fact into a quantified susceptibility factor and belongs at the intake end of the corpus's causal-pathway map, upstream of the neurosteroid and epigenetic findings.
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