Relationship between polymorphism of N-acetyltransferase gene and susceptibility to colorectal carcinoma in a Chinese population.

Human hepatic N-acetyltransferase (NAT2) is subject to a genetic polymorphism. Because NAT2 is an important enzyme for the detoxification and/or bioactivation of several carcinogenic arylamines, it has been postulated that the polymorphism of NAT2 gene is associated with the occurrence of colorectal and bladder carcinomas. Several mutations have been described in the human NAT2 gene that have been associated with reduced NAT2 activity. However, the majority are single base substitutions at positions 481 (NAT2*5A), 590 (NAT2*6A) and 857 (NAT2*7A) of the NAT2 gene. This study was performed to evaluate the relative distribution of NAT2 alleles and genotypes in 216 colorectal carcinoma patients and 187 normal individuals. The frequencies of NAT2 alleles and genotypes in the sampled Chinese population were characterized by allele-specific polymerase chain reaction. No differences were observed in the distribution of the genotypes coding rapid acetylation (homozygous wild-type and heterozygous wild-type with any of the mutations) when comparing colorectal carcinoma patients with control individuals (P > 0.05). However, the rapid acetylation genotype was associated with cancer occurring on the right site of the colon. The frequencies of the NAT2*4, NAT2*5A, NAT2*6A and NAT2*7A alleles of the NAT2 gene (0.51, 0.07, 0.32 and 0.10, respectively) in control individuals were significantly different from those in patients (0.49, 0.06, 0.26 and 0.19, respectively, P < 0.01). There was a significant increase in the frequency of patients who were compound heterozygotes of NAT2*7A and a variant non-NAT2*7A allele. The NAT2*7A allele was also seen more frequently in distal cancer.