Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population  

韩国人群中细胞色素CYP17A1 CYP3A4和CYP3A43基因的多态性与前列腺癌致癌风险和侵袭力的关系

作　　者：Jun Hyun Han Yong Seong Lee Hae Jong Kim Shin Young Lee Soon Chul Myung 

机构地区：[1]Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si 445-170, Korea [2]Department of Urology, Hallym University Kangnam Sacred Heart Hospital, Seoul 150-950, Korea [3]Advanced Urogenital Disease Research Center, Chung-Ang University College of Medicine, Seoul 156-756, Korea [4]Research Institute for Translational System Biomics, Chung-Ang University College of Medicine, Seoul 156-756, Korea [5]Department of Urology, Seoul Medical Center, Seoul 131-865, Korea [6]Department of Urology, Chung-Ang University Hospital, Seou1156-756, Korea.

出　　处：《Asian Journal of Andrology》2015年第2期285-291,I0010,共8页亚洲男性学杂志（英文版）

摘　　要：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 singie-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 （d = 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 [Cl], 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% Ch 1.04-3.68） and CYP17A1 Ht-4 （OR： 2.01; 95% Ch 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.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 singie-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 （d = 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 [Cl], 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% Ch 1.04-3.68） and CYP17A1 Ht-4 （OR： 2.01; 95% Ch 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.

关 键 词：ANDROGENS CYP17A1 CYP3A4 CYP3A43 GENETICS prostatic neoplasms 

分 类 号：R[医药卫生]