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CYP17 Promoter Variant Associated with Prostate Cancer Aggressiveness in African Americans¹

National Human Genome Center at Howard University [R. A. K., R. K. P., W. C., A. M., G. M. D.], Washington, DC 20059; Division of Urology, Howard University Hospital [R. A. K., C. A., A. J.], Washington, DC 20059; Howard University Cancer Center [R. A. K., F. U., L. A-C., G. M. D.], Washington, DC 20059; and The Johns Hopkins University Cancer Center, Baltimore, Maryland [W. I.]

Androgens play an important role in the etiology of prostate cancer. The CYP17 gene encodes the cytochrome P450c17 enzyme, which is the rate-limiting enzyme in androgen biosynthesis. A T to C polymorphism in the 5' promoter region has recently been associated with prostate cancer. However, contradictory data exists concerning the risk allele. To investigate further the involvement of the CYP17 variant with prostate cancer, we typed the polymorphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotyped the CYP17 polymorphism in Nigerian (n = 56), European-American (n = 74), and African-American (n = 111) healthy male volunteers, along with African-American men affected with prostate cancer (n = 71), using pyrosequencing. Genotype and allele frequencies did not differ significantly across the different control populations. African-American men with the CC CYP17 genotype had an increased risk of prostate cancer (odds ratio, 2.8; 95% confidence interval, 1.0–7.4) compared with those with the TT genotype. A similar trend was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was significantly associated with higher grade and stage of prostate cancer (odds ratio, 7.1; 95% confidence interval, 1.4–36.1). The risk did not differ significantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prostate cancer risk and clinically advanced disease in African Americans.

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