We have continued to explore cofactors that may influence the relationship between cigarette smoking and lung cancer risk. As summarized above in collaboration with Fung-Lung Chung of the American Health Foundation, we developed and validated, via a metabolic experiment, a urinary assay for total dietary isothiocyanate (ITC) exposure in humans. The primary source of ITC exposure in humans is via consumption of cruciferous vegetables, and we have quantified the total ITC contents of nine commonly consumed cruciferous vegetables among Chinese, which also include all commonly eaten cruciferous vegetables in western populations. Later, we demonstrated a highly significant correlation between dietary (based on a validated food frequency questionnaire) and urinary levels of ITC in Singapore Chinese, a highly-exposed population, thus validating the use of spot urine measurements as biomarkers of ITC exposures in epidemiologic studies. We also provided the first set of human data showing glutathione S-transferases (GSTs) as major catalysts for ITC metabolism.

ITCs are potent chemopreventive agents in animal models of lung carcinogenesis. As described above we recently reported on the first epidemiologic study showing an inverse and statistically significant association between personal levels of urinary ITC and lung cancer risk in Shanghai Chinese. Moreover, the protective effect of ITC was largely confined to subjects possessing the GST-null genotypes, an observation that is consistent with GSTs playing a major role in ITC excretion as we have noted earlier in Singapore Chinese.