CYP3A43 Pro340Ala Polymorphism and Prostate Cancer Risk in African Americans and Caucasians
- Angie Stone1,
- Luke D. Ratnasinghe1,3,4,
- Ginny L. Emerson1,
- Rama Modali6,
- Terri Lehman6,
- Gail Runnells3,
- Alindria Carroll3,
- Weleetka Carter3,
- Samuel Barnhart3,
- Al A. Rasheed3,
- Graham Greene3,
- Don E. Johnson2,
- Christine B. Ambrosone5,
- Fred F. Kadlubar1 and
- Nicholas P. Lang2,3,4
- 1Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas; 2Central Arkansas Veteran's Health Care System; 3Arkansas Cancer Research Center; and 4Department of Surgery, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas; 5Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York; and 6BioServe 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
Abstract
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 α-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.
- Cytochrome P450 3A43
- Prostate Cancer
- steroid hormones
- testosterone metabolism
- matrix-assisted laser desorption time-of-flight mass spectrometry
Footnotes
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Grant support: Arkansas Bioscience Institute, National Cancer Institute grant R01CA55751, National Institute on Aging grant R01AG15722-02, NIH GCRC grant M01RR14288, and National Center for Toxicological Research-Food and Drug Administration protocol E0702101. G.L. Emerson was supported as a postdoctoral research associate through the Oak Ridge Institute for Science and Education.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 2, 2004.
- Received July 19, 2004.
- Revision received November 4, 2004.
