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CYP3A43 Pro³⁴⁰Ala Polymorphism and Prostate Cancer Risk in African Americans and Caucasians

¹ Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas; ² Central Arkansas Veteran's Health Care System; ³ Arkansas Cancer Research Center; and ⁴ Department of Surgery, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas; ⁵ Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York; and ⁶ BioServe Biotechnologies, Inc., Laurel, Maryland

Requests for reprints: Angie Stone, Central Arkansas Veteran's Health Care System, Research Service Slot 151, 4301 West 7th Street, Little Rock, AR 72205. Phone: 501-257-4850; Fax: 501-257-4822. E-mail: Stoneannjanette{at}uams.edu

The human cytochrome P450 3A subfamily of enzymes is involved in the metabolism of steroid hormones, carcinogens, and many drugs. A cytosine-to-guanine polymorphism in CYP3A43 results in a proline-to-alanine substitution at codon 340. Although the functional significance of this polymorphism is unknown, we postulate that the substitution of proline, an -imino acid, with alanine, an amino acid, could be of biochemical significance. In a case-control study with 490 incident prostate cancer cases (124 African Americans and 358 Caucasians) and 494 controls (167 African Americans and 319 Caucasians), we examined the association between CYP3A43 Pro³⁴⁰Ala polymorphism and prostate cancer risk. When all subjects were considered, there was a 3-fold increase in risk of prostate cancer among individuals with the CYP3A43-Ala/Ala genotype (odds ratio, 3.0; 95% confidence interval, 1.2-7.2) compared with those with the CYP3A43-Pro/Pro genotype after adjusting for age, race, and smoking. The prevalence of the polymorphism was significantly higher in African Americans than Caucasians (45% versus 13%). In African Americans, there was a 2.6-fold increase in prostate cancer risk among individuals with the CYP3A43-Ala/Ala genotype (odds ratio, 2.6; 95% confidence interval, 1.0-7.0) compared with those with the CYP3A43-Pro/Pro genotype. Among Caucasians, the small number of homozygotes precluded computing risk estimates; there were only three individuals with the CYP3A43-Ala/Ala genotype. Our results suggest that the CYP3A43-Pro³⁴⁰Ala polymorphism contributes to prostate cancer risk.

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