Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma.

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.