Impact of a genetic variant in CYP3A4 on risk and clinical presentation of prostate cancer among white and African-American men

• Published in: Urologic oncology 2006, Vol.24 (1), p.21-27
• Main Authors: Bangsi, Dieudonne, Zhou, JunYing, Sun, Yezhou, Patel, Nimesh P., Darga, Linda L., Heilbrun, Lance K., Powell, Isaac J., Severson, Richard K., Everson, Richard B.
• Format: Article
• Language: English
• Subjects: African Americans - genetics; Aged; Biological and medical sciences; Case-Control Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - genetics; European Continental Ancestry Group - genetics; Genetic polymorphisms; Genetic Predisposition to Disease; Genotype; Humans; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Odds Ratio; Polymorphism, Genetic; Prognosis; Prostate cancer; Prostatic Neoplasms - genetics; Racial disparity; Risk Factors; Tumors; Tumors of the urinary system; Urban Population; Urinary tract. Prostate gland
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2005.09.005

Genes involved in androgen metabolism are strong candidates for having an important role in the pathogenesis of prostate cancer. CYP3A4, a protein in the cytochrome P-450 supergene family, facilitates the oxidative deactivation of testosterone. In previous studies, patients with the G variant of a genetic polymorphism in CYP3A4 had prostate cancers with clinically aggressive characteristics at diagnosis. The association was strongest among elderly men. We investigated whether the CYP3A4 variant was linked with the diagnosis or clinical presentation of prostate cancer in a case control study of a multiethnic urban population. Biologic specimens were genotyped for CYP3A4, and analyzed for the impact of this genotype on risk and tumor characteristics at presentation, controlling for the effect of several cofactors. The CYP3A4 variant was more common among African-Americans than among white men. Race-stratified analyses revealed little association between the CYP3A4 variant and prostate cancer risk among white men but were limited by the small number of white men with the CYP3A4 variant. Of African-American men, while the variant G allele was not associated with prostate cancer that had less aggressive characteristics, it was associated with risk of aggressive prostate cancer when men with the AG genotype (odds ratio = 9.3, 95% confidence interval 1.3−411) or GG genotype (odds ratio = 11.9 95% confidence interval 1.6−533) were compared with those with the AA genotype. The association between the CYP3A4 genotype and aggressive prostate cancer in African-American men is consistent with findings of other studies.