The V89L polymorphism in the 5 alpha-reductase type 2 gene and risk of prostate cancer

5 alpha-Reductase type 2, the predominant prostatic isozyme of this protein , converts testosterone to dihydrotestosterone. It has been hypothesized th at individuals with greater 5 alpha-reductase activity are at increased ris k for prostate cancer (CaP). A single nucleotide polymorphism of the 5 alph a-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (l eu) for valine (val) at codon 89 (V89L), the, presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect. of th is polymorphism on the risk of prostate cancer in a prospective, nested, ca se-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasm a AAG levels available, there mac; no significant association between AAG l evels and V89L genotype. We also detected no significant association betwee n risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% conf idence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be com pletely excluded.