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 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 GSTM1 (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.