title: CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk in African Americans and Caucasians.
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 alpha-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 Pro(340)Ala 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-Pro(340)Ala polymorphism contributes to prostate cancer risk.
authors.affiliation: Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR, USA. Stoneannjanette@uams.edu
authors.forename: Angie
authors.initials: A
authors.lastname: Stone
authors.forename: Luke D
authors.initials: LD
authors.lastname: Ratnasinghe
authors.forename: Ginny L
authors.initials: GL
authors.lastname: Emerson
authors.forename: Rama
authors.initials: R
authors.lastname: Modali
authors.forename: Terri
authors.initials: T
authors.lastname: Lehman
authors.forename: Gail
authors.initials: G
authors.lastname: Runnells
authors.forename: Alindria
authors.initials: A
authors.lastname: Carroll
authors.forename: Weleetka
authors.initials: W
authors.lastname: Carter
authors.forename: Samuel
authors.initials: S
authors.lastname: Barnhart
authors.forename: Al A
authors.initials: AA
authors.lastname: Rasheed
authors.forename: Graham
authors.initials: G
authors.lastname: Greene
authors.forename: Don E
authors.initials: DE
authors.lastname: Johnson
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Fred F
authors.initials: FF
authors.lastname: Kadlubar
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Lang
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000409:Alanine / Q000235:genetics; D001131:Arkansas / Q000453:epidemiology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D011392:Proline; D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; D000409:Alanine