London S J, Yuan J M, Chung F L, Gao Y T, Coetzee G A, Ross R K, Yu M C
USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
Lancet. 2000 Aug 26;356(9231):724-9. doi: 10.1016/S0140-6736(00)02631-3.
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.
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.
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 GSTM1 (0.36 [0.20-0.63]) and particularly with deletion of both GSTM1 and GSTT1 (0.28 [0.13-0.57]).
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.
膳食异硫氰酸盐可抑制实验动物的肺癌发生，但相关人体数据有限。谷胱甘肽S-转移酶M1和T1（GSTM1和GSTT1）可使异硫氰酸盐结合，从而加速其清除。GSTM1和GSTT1常见的缺失多态性会导致酶活性丧失。我们推测，当缺乏增强异硫氰酸盐清除的酶时，其化学预防作用可能会增强。
我们检测了中国上海18244名男性队列中232例肺癌新发病例和710名匹配对照在诊断前收集的尿液中总异硫氰酸盐浓度与随后患肺癌风险之间的关系，该队列随访时间为1986年至1997年。通过聚合酶链反应（PCR）确定GSTM1和GSTT1基因的纯合缺失情况。
尿液中可检测到异硫氰酸盐的个体患肺癌的风险降低（调整吸烟因素后的肺癌相对风险=0.65[95%可信区间0.43 - 0.97]）。异硫氰酸盐的这种保护作用主要见于GSTM1纯合缺失的个体（0.36[0.20 - 0.63]），尤其是同时缺失GSTM1和GSTT1的个体（0.28[0.13 - 0.57]）。
异硫氰酸盐似乎降低了该中国男性队列中的肺癌风险。在基因上缺乏能快速清除这些化学预防化合物的酶的人群中，风险降低最为显著。
