V89L polymorphism of the 5alpha-reductase Type II gene (SRD5A2), endogenous sex hormones, and prostate cancer risk.
We examined the combined effect of circulating sex hormones and SRD5A2 V89L polymorphism on prostate cancer risk in a case-control study (300 cases and 300 controls) nested within the Carotene and Retinol Efficacy Trial. A moderate increase in risk associated with above-median serum levels of androstenedione and dehydroepiandrosterone sulfate (DHEAS) was present irrespective of V89L genotype. However, in L/L or V/L men, above-median DHEAS levels were associated with an increased risk of aggressive tumors [odds ratios (OR), 3.12; 95% confidence interval (95% CI), 1.28-7.63] but not of nonaggressive ones (OR, 0.56; 95% CI, 0.25-1.25). Above-median serum levels of free estradiol were associated with a lower risk, especially for aggressive cancer. The association with aggressive disease was more pronounced in men with a V/V genotype (OR, 0.34; 95% CI, 0.14-0.81), than in men with an L/L or V/L genotype (OR, 0.77; 95% CI, 0.37-1.60). Above-median levels of 3alpha-diol G were associated with an increased risk, but only in men with the L/L or V/L genotype (OR, 2.16; 95% CI, 1.31-3.56). The increase in risk in L/L and V/L men was restricted to aggressive tumors. Our study observed that only in men with the L/L or V/L genotype were increased serum levels of DHEAS and 3alpha-diol G positively associated with a higher risk of aggressive prostate cancer. Free estradiol levels were negatively associated with risk of aggressive prostate cancer in men with the V/V genotype. However, the absence of an overall association between V89L genotype and aggressive prostate cancer argues for a cautious interpretation of these observations.
Boger-Megiddo
Inbal
I
Program in Epidemiology, Division of Public Health, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Weiss
Noel S
NS
Barnett
Matt J
MJ
Goodman
Gary E
GE
Chen
Chu
C
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors
D012739:Gonadal Steroid Hormones; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase