Hein D W, Doll M A, Fretland A J, Leff M A, Webb S J, Xiao G H, Devanaboyina U S, Nangju N A, Feng Y
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Kentucky 40292, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):29-42.
The focus of this review is the molecular genetics, including consensus NAT1 and NAT2 nomenclature, and cancer epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Two N-acetyltransferase isozymes, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation (usually deactivation) and O-acetylation (usually activation) of aromatic and heterocyclic amine carcinogens. Epidemiological studies suggest that the NAT1 and NAT2 acetylation polymorphisms modify risk of developing urinary bladder, colorectal, breast, head and neck, lung, and possibly prostate cancers. Associations between slow NAT2 acetylator genotypes and urinary bladder cancer and between rapid NAT2 acetylator genotypes and colorectal cancer are the most consistently reported. The individual risks associated with NAT1 and/or NAT2 acetylator genotypes are small, but they increase when considered in conjunction with other susceptibility genes and/or aromatic and heterocyclic amine carcinogen exposures. Because of the relatively high frequency of some NAT1 and NAT2 genotypes in the population, the attributable cancer risk may be high. The effect of NAT1 and NAT2 genotype on cancer risk varies with organ site, probably reflecting tissue-specific expression of NAT1 and NAT2. Ethnic differences exist in NAT1 and NAT2 genotype frequencies that may be a factor in cancer incidence. Large-scale molecular epidemiological studies that investigate the role of NAT1 and NAT2 genotypes and/or phenotypes together with other genetic susceptibility gene polymorphisms and biomarkers of carcinogen exposure are necessary to expand our current understanding of the role of NAT1 and NAT2 acetylation polymorphisms in cancer risk.
本综述的重点是分子遗传学，包括NAT1和NAT2的一致命名法，以及NAT1和NAT2乙酰化多态性的癌症流行病学。两种N - 乙酰转移酶同工酶NAT1和NAT2具有多态性，可催化芳香族和杂环胺类致癌物的N - 乙酰化（通常为失活）和O - 乙酰化（通常为活化）。流行病学研究表明，NAT1和NAT2乙酰化多态性会改变患膀胱癌、结直肠癌、乳腺癌、头颈癌、肺癌以及可能的前列腺癌的风险。NAT2慢乙酰化基因型与膀胱癌之间以及NAT2快乙酰化基因型与结直肠癌之间的关联是报道最为一致的。与NAT1和/或NAT2乙酰化基因型相关的个体风险较小，但与其他易感基因和/或芳香族及杂环胺类致癌物暴露同时考虑时，风险会增加。由于人群中某些NAT1和NAT2基因型的频率相对较高，因此可归因的癌症风险可能较高。NAT1和NAT2基因型对癌症风险的影响因器官部位而异，这可能反映了NAT1和NAT2的组织特异性表达。NAT1和NAT2基因型频率存在种族差异，这可能是癌症发病率的一个影响因素。有必要开展大规模分子流行病学研究，调查NAT1和NAT2基因型和/或表型与其他遗传易感基因多态性以及致癌物暴露生物标志物的共同作用，以扩展我们目前对NAT1和NAT2乙酰化多态性在癌症风险中作用的理解。
