Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms

The focus of this review is the molecular genetics, including consensus NAT 1 and NAT2 nomenclature, and cancer epidemiology of the NAT1 and NAT2 acety lation polymorphisms. Two N-acetyltransferase isozymes, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation (usually deactivation) and O-ac etylation (usually activation) of aromatic and heterocyclic amine carcinoge ns. Epidemiological studies suggest that the NAT1 and NAT2 acetylation poly morphisms modify risk of developing urinary bladder, colorectal, breast, he ad and neck, lung, and possibly prostate cancers. Associations between slow NAT2 acetylator genotypes and urinary bladder cancer and between rapid NAT 2 acetylator genotypes and colorectal cancer are the most consistently repo rted. The individual risks associated with NAT1 and/or NAT2 acetylator geno types are small, but they increase when considered in conjunction with othe r susceptibility genes and/or aromatic and heterocyclic amine carcinogen ex posures. Because of the relatively high frequency of some NAT1 and NAT2 gen otypes in the population, the attributable cancer risk may be high. The eff ect of NAT1 and NAT2 genotype on cancer risk varies with organ site, probab ly reflecting tissue-specific expression of NAT1 and NAT2, Ethnic differenc es exist in NAT1 and NAT2 genotype frequencies that may be a factor in canc er incidence, Large-scale molecular epidemiological studies that investigat e the role of NAT1 and NAT2 genotypes and/or phenotypes together with other genetic susceptibility gene polymorphisms and biomarkers of carcinogen exp osure are necessary to expand our current understanding of the role of NAT1 and NAT2 acetylation polymorphisms in cancer risk.