Ma Qing-Wen, Lin Guo-Fang, Chen Ji-Gang, Xiang Cui-Qing, Guo Wei-Chao, Golka Klaus, Shen Jian-Hua
Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
Biomed Environ Sci. 2004 Sep;17(3):291-8.
Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism.
NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A.
The wild allele NAT2 4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT26A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P < 0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients.
The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.
芳胺N - 乙酰基转移酶(NATs)参与芳香胺和肼的解毒过程。为了探讨在中国联苯胺暴露或未暴露个体中NAT2基因多态性与膀胱癌风险之间的可能关联,对健康受试者、上海染料行业中联苯胺暴露队列的膀胱癌患者以及一组无已知芳香胺职业暴露史的膀胱癌患者进行了NAT2基因多态性基因分型。
采用一组限制性片段长度多态性(RFLP)程序对基因编码区的七个主要多态性位点进行NAT2基因分型:G191A、C282T、T341C、C481T、G590A、A803G和G857A。
野生型等位基因NAT2 4是健康个体中最常见的等位基因(59%)。等位基因NAT26A和NAT2*7B也经常被观察到(分别为21%和17%)。与白种人相比,慢乙酰化者的比例较低(中国人中为12%,白种人中为58%;P < 0.001)。在健康受试者与两组膀胱癌患者之间,对于纯合快速、杂合快速/慢和纯合慢乙酰化基因型未观察到相关差异。
本研究不支持NAT2基因的慢乙酰化基因型与中国人群膀胱癌风险升高之间存在关联,而在白种人中它被证明是一个重要的遗传决定风险因素。不同机制可能在不同种族或民族中与芳香胺暴露相关的膀胱癌个体易感性中起作用。