Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer

Abstract

The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 *5A), M2 (NAT2*6A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancer patients and controls in the WT, M2 and M3 alleles (p < 0.05). However, only M2 and M3 allele frequencies were different between colorectal cancer patients and controls (p < 0.05). There was a marginal significant difference in the distribution of rapid and slow acetylator genotypes between lung cancer patients and controls (p = 0.06 and p = 0.05, respectively), but not between colorectal cancer patients and controls (p = 1.0 and p = 0.95, respectively). Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR): 0.51, 95% confidence interval (95% CI): 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectal cancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectal cancer susceptibility in Jordan.

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“…19 The nat2*6 allele was among the most frequent alleles in populations of European and African descent, whereas nat2*7 was specific to the Asian population. 20,21 With respect to nat2 gene phenotypes, intermediate metabolizers were dominant (61.4%) in the north of Cameroon. This results were similar to those obtained previously in Garoua, Mutengene and Bangolan, where slow and intermediate metabolizers dominated.…”

Effects of NAT2 Polymorphism on Lung Cancer Risk, and the Interaction Between Smoking and NAT2: A Meta-analysis

“…Individual differences in activities of these enzymes can in uence the biological responses to xenobiotic exposure, cancer susceptibility, and eventual adverse drug reactions [5,6]. N-acetyltransferase 2 (NAT2) is polymorphic and widely exists in lung, colon, breast, prostate and liver [7]. Nacetylation (deactivation) and O-acetylation (activation) of a variety of HCAs, PAHs and other carcinogens can be catalyzed by NAT2 [8].…”

“…Nacetylation (deactivation) and O-acetylation (activation) of a variety of HCAs, PAHs and other carcinogens can be catalyzed by NAT2 [8]. The main function of NAT2 is to transfer an acetyl group from acetyl CoA to the nitrogen of the substrate [7]. Polymorphisms of the NAT2 gene locus led to the difference of NAT2 enzyme activity between different individuals [9].…”

“…Polymorphisms of the NAT2 gene locus led to the difference of NAT2 enzyme activity between different individuals [9]. Rapid acetylation phenotype, intermediate phenotype and slow acetylation phenotype are the three phenotypes of NAT2 [7]. The rapid acetylation phenotype consists of two copies of wild type alleles (WT) [7].…”

“…Rapid acetylation phenotype, intermediate phenotype and slow acetylation phenotype are the three phenotypes of NAT2 [7]. The rapid acetylation phenotype consists of two copies of wild type alleles (WT) [7]. The intermediate phenotype consists of a wild type allele and a mutant allele [7].…”