Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China
Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China
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DOI：
10.1016/s0140-6736(00)02631-3
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发表时间：
2000-08-26
期刊：
影响因子：
168.9
通讯作者：
Yu, MC
中科院分区：
文献类型：
--
作者：
London, SJ;Yuan, JM;Yu, MC
在实验动物中，饮食中的异硫氰酸酯抑制肺癌的发生，但人类的数据有限。谷胱甘肽s -转移酶M1和T1 （GSTM1和GSTT1）结合异硫氰酸酯导致更快的消除，GSTM1和GSTT1的常见缺失多态性会破坏酶的活性。我们假设，当缺乏促进其消除的酶时，异硫氰酸酯的化学预防作用可能会增强。方法对1986年至1997年在中国上海进行随访的18244例男性肺癌患者中的232例和710例对照者进行诊断前尿液中总异硫氰酸盐浓度与肺癌发病风险的关系分析。采用PCR检测GSTM1和GSTT1基因的纯合缺失。发现尿液中检测到异硫氰酸酯的个体患肺癌的风险降低（吸烟调整后肺癌的相对风险=0.65 [95% CI 0.43-0.97]）。异硫氰酸酯的这种保护作用主要出现在GSTT1纯合缺失的个体中（0.36[0.20-0.63]），特别是GSTM1和GSTT1同时缺失的个体（0.28[0.13-0.57]）。解释异硫氰酸酯似乎降低了中国男性患肺癌的风险。在基因上缺乏能迅速消除这些化学预防化合物的酶的人群中，风险的降低幅度最大。
Background Dietary isothiocyanates inhibit lung carcinogenesis in laboratory animals but human data are limited. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) conjugate isothiocyanates leading to more rapid elimination, Common deletion polymorphisms of GSTM1 and GSTT1 abolish enzyme activity. We hypothesised that chemopreventive effects of isothiocyanates might be heightened when enzymes that enhance their elimination are lacking.Methods We examined the relation between total isothiocyanate concentrations in urine, collected before diagnosis, and the subsequent risk of lung cancer among 232 incident cases of lung cancer and 710 matched controls from a cohort of 18 244 men in Shanghai, China, followed from 1986 to 1997. Homozygous deletion of the GSTM1 and GSTT1 genes were determined by PCR.Findings Individuals with detectable isothiocyanates in the urine were at decreased risk of lung cancer (smoking-adjusted relative risk for lung cancer=0.65 [95% CI 0.43-0.97]). This protective effect of isothiocyanates was seen primarily among individuals with homozygous deletion of GSTT1 (0.36 [0.20-0.63]) and particularly with deletion of both GSTM1 and GSTT1 (0.28 [0.13-0.57]).Interpretation Isothiocyanates appeared to reduce lung-cancer risk in this cohort of Chinese men. Reduction in risk was strongest among persons genetically deficient in enzymes that rapidly eliminate these chemopreventive compounds.