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The Relationship between a Polymorphism in CYP17 with Plasma Hormone Levels and Prostate Cancer¹

Departments of Epidemiology [C. A. H., M. J. S., E. G., D. J. H.] and Nutrition [M. J. S., E. G., D. J. H.] and the Harvard Center for Cancer Prevention [C. A. H., D. J. H.], Harvard School of Public Health, Boston, Massachusetts 02115; Channing Laboratory [M. J. S., E. G., J. M., D. J. H.], Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts 02115; Lank Center for Genitourinary Oncology [P. W. K.] and the Department of Adult Oncology [N. E. D., P. W. K.], Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the Department of Preventive Medicine [C. A. H.], University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90089

The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men and women. We prospectively assessed the association between the A2 allele of CYP17 and prostate cancer risk among 590 cases and 782 controls in a case-control study nested within the Physicians’ Health Study cohort. We also evaluated associations between CYP17 genotype and plasma steroid hormones among controls and the potential interaction between CYP17 and SRD5A2 V89L polymorphisms in relationship with prostate cancer risk and circulating steroid hormone levels. We observed a borderline significant association between the A2 allele and prostate cancer risk (odds ratio, 1.23; 95% confidence interval, 0.99–1.54), however, we did not observe evidence of a gene-dosage effect (versus A1/A1 genotype: A1/A2 genotype; odds ratio, 1.26; 95% confidence interval, 0.99–1.59; A2/A2 genotype: odds ratio, 1.17; 95% confidence interval, 0.85–1.61). The A2 allele was not overrepresented among cases with advanced prostate cancer. Among controls, carriers of the A2 allele had steroid hormone levels similar to noncarriers. We also found no evidence of a gene-gene interaction between CYP17 and SRD5A2 V89L polymorphisms on prostate cancer risk or endogenous steroid hormone levels. These results suggest that CYP17 genotype may possibly confer a small increased susceptibility to prostate cancer but is not a strong predictor of endogenous steroid hormone levels in men.

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