TY - JOUR
T1 - The V89L polymorphism in the 5α-reductase type 2 gene and risk of prostate cancer
AU - Febbo, Phillip G.
AU - Kantoff, Philip W.
AU - Platz, Elizabeth A.
AU - Casey, Daniel
AU - Batter, Steve
AU - Giovannucci, Edward
AU - Hennekens, Charles H.
AU - Stampfer, Meir J.
PY - 1999/12/1
Y1 - 1999/12/1
N2 - 5α-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5α-reductase activity are at increased risk for prostate cancer (CAP). A single nucleotide polymorphism of the 5α-reductase type 2 gene (SRDSA2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case- control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between 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% confidence 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 completely excluded.
AB - 5α-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5α-reductase activity are at increased risk for prostate cancer (CAP). A single nucleotide polymorphism of the 5α-reductase type 2 gene (SRDSA2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case- control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between 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% confidence 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 completely excluded.
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M3 - Article
C2 - 10606227
AN - SCOPUS:0033233173
SN - 0008-5472
VL - 59
SP - 5878
EP - 5881
JO - Cancer Research
JF - Cancer Research
IS - 23
ER -