Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China

Background Dietary isothiocyanates inhibit lung carcinogenesis in laborator y animals but human data are limited. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) conjugate isothiocyanates leading to more rapid eliminati on, Common deletion polymorphisms of GSTM1 and GSTT1 abolish enzyme activit y. 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 concentration s in urine, collected before diagnosis, and the subsequent risk of lung can cer 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. Homoz ygous deletion of the GSTM1 and GSTT1 genes were determined by PCR. Findings Individuals with detectable isothiocyanates in the urine were at d ecreased risk of lung cancer (smoking-adjusted relative risk for lung cance r=0.65 [95% CI 0.43-0.97]). This protective effect of isothiocyanates was s een 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 [0.1 3-0.57]). Interpretation Isothiocyanates appeared to reduce lung-cancer risk in this cohort of Chinese men. Reduction in risk was strongest among persons geneti cally deficient in enzymes that rapidly eliminate these chemopreventive com pounds.