title: Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population.
abstract: In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1), locations (SNPs in exons were preferred), and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18) was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43) was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68) and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11) showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.
authors.forename: Jun Hyun
authors.initials: JH
authors.lastname: Han
authors.forename: Yong Seong
authors.initials: YS
authors.lastname: Lee
authors.forename: Hae Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Advanced Urogenital Disease Research Center; Research Institute for Translational System Biomics; Department of Urology, Chung-Ang University Hospital, Seoul 156-756, Korea.
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Myung
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D012720:Severity of Illness Index; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; D051544:Cytochrome P-450 CYP3A; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; C510163:CYP3A4 protein, human