Prawan A, Kukongviriyapan V, Tassaneeyakul W, Pairojkul C, Bhudhisawasdi V
Department of Pharmacologygery, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, 40002, Thailand.
Eur J Cancer Prev. 2005 Jun;14(3):245-50. doi: 10.1097/00008469-200506000-00008.
Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and 1F), six NAT1 alleles (NAT14 wild-type, *3, *10, *11, *14A and 14B) and seven NAT2 alleles (NAT24 wild-type, *5, 6A, 6B, 7A, 7B and 13), which are the major alleles found in most populations, were analysed. Although CYP1A21A allele, NAT110 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A21A/1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A21F/1F. Frequency distributions of rapid NAT213 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA.
人类细胞色素P450 1A2（CYP1A2）和芳胺N - 乙酰基转移酶分别由多态性的CYP1A2和NAT基因编码，已显示其代谢能力存在广泛的个体差异，并且可能是个体对某些类型癌症易感性的潜在调节因子。本研究旨在评估CYP1A2、NAT1和NAT2基因多态性与胆管癌（CCA）之间的关系，胆管癌是泰国东北部最常见的癌症。通过基于聚合酶链反应和限制性片段长度多态性的检测方法，对总共216例CCA患者和233例对照受试者进行基因分型。分析了两个CYP1A2等位基因（CYP1A21A野生型和1F）、六个NAT1等位基因（NAT1*4野生型、*3、10、11、14A和14B）以及七个NAT2等位基因（NAT24野生型、5、6A、6B、7A、7B和13），这些是大多数人群中发现的主要等位基因。尽管CYP1A21A等位基因、NAT110等位基因和NAT2慢乙酰化酶等位基因与CCA风险无关，但在男性受试者中，与CYP1A21F/1F相比，CYP1A21A/1A基因型使患癌风险降低（调整后的优势比（OR）为0.28，95%置信区间（CI）为0.08 - 0.94）。快速NAT213以及两个慢等位基因（6B和7A）的频率分布与较低的CCA风险相关，但其他主要等位基因则不然。与不包含这些等位基因的基因型相比，由这些等位基因中至少一个组成的基因型的调整后OR显著降低了患癌风险（OR为0.26，95% CI为0.15 - 0.44）。本研究表明，NAT2基因多态性可能是个体患CCA风险的调节因子。
