title: A polymorphism in the CYP17 gene and risk of prostate cancer.
abstract: Steroid hormones are important in the etiology and progression of prostate cancer, and expression of genes involved in hormone production may alter susceptibility. One such gene is CYP17, which encodes the cytochrome P450c17a enzyme responsible for the biosynthesis of testosterone. A T to C transition (A2 allele) in the 5' promoter region of the gene is hypothesized to increase the rate of gene transcription, increase androgen production, and thereby increase risk of prostate cancer. To test this hypothesis, germ-line DNA samples from a large population-based study of incident prostate cancer cases (n = 590) and controls (n = 538) of similar age without the disease were genotyped. The frequency of the A2 allele was similar in cases and controls. Compared with men with the A1/A1 genotype, the adjusted odds ratio was 0.81 for the A1/A2 and 0.87 for the A2/A2 genotype. Risk estimates did not vary substantially by age or race. However, stratification by family history of prostate cancer revealed that among white men with an affected first-degree relative, homozygotes for the A2 allele had a significant elevation in risk (odds ratio = 19.2; 95% confidence interval, 2.2-157.4) compared with men who were homozygous for the A1 allele (interaction P = 0.0005). These results suggest that the CYP17 A2/A2 genotype predicts susceptibility to prostate cancer in white men with a family history of the disease. It is also possible that CYP17 interacts with other genes that influence risk of familial prostate cancer.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle 98109, USA. jstanfor@fhcrc.org
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Noonan
authors.forename: Lori
authors.initials: L
authors.lastname: Iwasaki
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.forename: Robert B
authors.initials: RB
authors.lastname: Chadwick
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism*; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D014861:Washington / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D000728:Androgens; D013254:Steroid 17-alpha-Hydroxylase