Carcinogenesis, Vol. 20, No. 9, 1727-1731,
September 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2)
Laboratory of Computational Biology and Risk Assessment and
1 Epidemiology Branch and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 and
2 Department of Surgery, Division of Urology, University of North Carolina, Chapel Hill, NC, USA
Prostate cancer is the most common malignancy in males and is the second most common cause of cancer mortality in American men. Polymorphisms have been identified in two genes, the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5-reductase type II gene (SRD5A2) that are involved with androgen biosynthesis and metabolism. The CYP17 A2 allele contains a T
C transition in the 5' promoter region that creates an additional Sp1-type (CCACC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels. We tested genotypes in 108 prostate cases and 167 controls along with samples (n = 340) from several different ethnic groups. The CYP17 A2 allele (combined A1/A2 and A2/A2 genotypes) occurred at a higher frequency in Caucasian patients with prostate cancer (70%) than in Caucasian clinical control urology patients (57%), suggesting that the A2 allele may convey increased risk for prostate cancer [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.0–3.0]. Blacks and Caucasians had a similar frequency of the A2 genotype (16 and 17%, respectively) while Taiwanese had the highest frequency (27%). The SRD5A2 leucine genotype was most frequent in Taiwanese (28%), intermediate in Caucasians (8.5%) and lowest in Blacks (2.5%). Genotypes having a SRD5A2 leucine allele were somewhat more common in prostate cancer cases (56%) than in controls (49%) (OR = 1.4, 95% CI = 0.8–2.2) but this difference was not significant. These results support the hypothesis that some allelic variants of genes involved in androgen biosynthesis and metabolism may be associated with prostate cancer risk.
Abbreviations: AR, androgen receptor; AR–DHT, androgen receptor–dihydroxytestosterone complex; BPH, benign prostate hypertrophy; CI, confidence interval; CYP17, 17-hydroxylase cytochrome P450; DHT, dihydroxytestosterone; OR, odds ratio; PCR, polymerase chain reaction; SRD5A2, steroid 5-reductase type II.
3 To whom correspondence should be addressed at Molecular and Genetic Epidemiology Section, NIEHS, Mail Drop A3–05, PO Box 12233, Research Triangle Park, NC 27709, USA Email: taylor{at}niehs.nih.gov
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