N-乙酰转移酶的多态性及其对肿瘤风险性的影响

N-乙酰转移酶是Ⅱ相药物代谢酶,在人体内由两个不同的基因编码,产生两个同酶NAT1和NAT2。NAT2的表达具有多态性,其慢乙酰化表型为NAT2基因编码区点突变所致。NAT1亦具有基因结构上的变异,不同的突变等位基因其酶表达水平不同。生化学研究表明NAT1和NAT2在致癌物质的代谢激活或灭活过程中起重要作用。流行病学研究则提示NATs的多态性与某些肿瘤的风险性有关,代谢基因型/表现型将通过影响DNA结合物的水平进而影响肿瘤的发生。如果肿瘤的遗传易感性这一生物标记能够成功地建立起来,将有助于更好地预防和控制人类疾病。

N-acetyltransferase polymorphism:effect on risk of cancer

N-acetyltransferase are phase II code proteins with overlapping substrate specifici-DMEs, and two highly similar human NAT gene ty. NAT2 is a polymorphic acetyltransferase gene (designated NAT1 and NAT2) are shown to en- locus and "slow acetylation" in humans is due tonutations in the single coding exon of the NAT2 gene. It was also demonstrated that there exist discrete NAT1 structural variants, and differences in tissue levels of NAT1 among humans are related to specific sequence differences in the NAT1 structural gene. Biochemical studies have shown that NAT1 and NAT2 play an important role in the metabolism of some carcinogens, epidemiological studies have revealed an association between ploy-morphisms of NATs and increased cancer risk.Metabolic phenotypes/genotypes can significantly influence DAN adduct formation and could ultimately lead to alterations in cancer risk. If unequivocal biomarkers of genetic susceptibility to cancer can be developed successfully, then identification of individuals at increased risk would be very helpful in the fields of public health and preventive medicine.