CYP17 promoter variant associated with prostate cancer aggressiveness in African Americans

Androgens play an important role in the etiology of prostate cancer. The CY P17 gene encodes the cytochrome P450c17 alpha enzyme, which is the rate-lim iting enzyme in androgen biosynthesis. A T to C polymorphism in the 5' prom oter region has recently been associated with prostate cancer. However, con tradictory data exists concerning the risk allele. To investigate further t he involvement of the CYP17 variant with prostate cancer, we typed the poly morphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotype d 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 dif ferent 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 tren d was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was sig nificantly 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 sig nificantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prosta te cancer risk and clinically advanced disease in African Americans.