Chinese populations consume a diet relatively high in
isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have
cancer-protective effects. This class of compounds is metabolized by the
glutathione S-transferase family of
enzymes, which are also involved in the detoxification of tobacco-related
carcinogens such as
polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary
isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and
lung cancer risk in 420 Chinese women: 233 histologically confirmed
lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in
DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of
lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (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 risk 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 nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation 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.