Dietary isothiocyanates, glutathione S-transferase-M1,-T1 polymorphisms and lung cancer risk among Chinese women in Singapore

Chinese populations consume a diet relatively high in isothiocyanates (ITCs ), a derivative of cruciferous vegetables known to have cancer-protective e ffects. This class of compounds is metabolized by the glutathione S-transfe rase family of enzymes, which are also involved in the detoxification of to bacco-related carcinogens such as polycyclic aromatic hydrocarbons and alky l halides. We evaluated the association between dietary isothiocyanate inta ke, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese wome n: 233 histologically confirmed lung cancer patients and 187 hospital contr ols. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmo kers. An allele-specific PCR method was used to detect the presence or abse nce of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Hig her weekly intake of ITCs (above the control median value of 53.0 mu mol) r educed the risk of lung cancer to a greater extent in smokers [adjusted odd s ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmoker s (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the r isk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsm okers this effect may be primarily confined to GST-null individuals. Conjug ation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.