Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients

Prostate cancer incidence, clinical presentation, and mortality rates vary among different ethnic groups. A genetic variant of CYP3A4, a gene involved in the oxidative deactivation of testosterone, has been associated recentl y with prostate cancer development in Caucasians, To further investigate th is variant, we evaluated its genotype frequencies in different ethnic group s and its association,vith clinical presentation of prostate cancer in Afri can Americans. CYP3A4 genotypes were assayed in healthy male Caucasian (n = 117), Hispanic (n = 121), African-American (n = 116), Chinese (n = 46), an d Japanese (n = 34) volunteers using the TaqMan assay. The association betw een CYP3A4 genotype and prostate cancer presentation was determined in 174 affected African-American men. Genotype frequency of the CYP3A4 variant dif fered substantially across ethnic groups, with African Americans much more likely to carry one or two copies than any other group (two-sided P < 0.000 1), Among African Americans, 46% (80 of 174) of men with prostate cancer we re homozygous for the CYP3A4 variant, whereas only 28% (32 of 116) of Afric an-American healthy volunteers were homozygous (two-sided P < 0.005), A con sistent positive association was observed between being homozygous for the CYP3A4 variant in African-American prostate cancer patients and clinical ch aracteristics. Men homozygous for the CYP3A4 variant were more likely to pr esent with higher grade and stage of prostate cancer in a recessive model [ odds ratio (OR), 1.7; 95% confidence interval (CI), 0.9-3.4]. This associat ion was even stronger for men who were >65 years of age at diagnosis (n = 1 03; OR, 2.4; 95% CI, 1.1-5.4). In summary, the CYP3A4 genotype frequency in different ethnic groups broadly followed trends in prostate cancer inciden ce, presentation, and mortality in the United States. African-American pros tate cancer patients had a higher frequency of being homozygous for the CYP 3A4 variant than healthy African-American volunteers who were matched solel y based on ethnicity. Among the patients, those who were homozygous for the CYP3A4 variant were more likely to present with clinically more advanced p rostate cancer.