Urinary Total Isothiocyanate (ITC) in a Population-based Sample of Middle-Aged and Older Chinese in Singapore: Relationship with Dietary Total ITC and Glutathione S-Transferase Mi/Ti/Pi

Isothiocyanates (ITCs), degradation products of glucosinolates (which occur naturally in a variety of cruciferous vegetables), have been shown to exhibit chemopreventive activity. These compounds are metabolized in vivo to form the corresponding dithiocarbamates, which are the major urinary metabolites of ITCs, by a pathway involving the glutathione S-transferase (GST) class of enzymes. Using a newly developed assay that measures total ITC (primarily ITC conjugates) in urine, we examined the relationships between cruciferous vegetable intake (obtained from a food frequency/portion size questionnaire administered in person); dietary total ITC level; GSTMJ, GSTTJ, and GSTPJ genotypes; and levels of total ITC in spot urine samples collected from 246 Singapore Chinese (111 men and 135 women), ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Consumption level of cruciferous vegetables was high in study subjects (mean consumption = 345 times per year, mean daily intake = 40.6 g), which was >3 times the comparable level of intake in the United States. Mean daily intake of total ITC among study subjects was 9.1 mol, and there was a 2.5-fold difference between the 25th and 75th percentile values. Seventy-three % of study subjects tested positive for ITC in urine, and there was a 4-fold difference between the 25th and 75th percentile values among the positive subjects. There was a highly significant positive association between dietary intake and urinary excretion levels of total ITC (two-sided P Received 1/16/98; revised 6/5/98; accepted 6/16/98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. I Supported by National Cancer Institute Grant R35 CA53890. 2 To whom requests for reprints should be addressed, at USC/Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles. CA 90033-0800. 0.0003) that was stronger than the association between overall cruciferous vegetable intake and urinary ITC level, which also was statistically significant (P 0.0004). There was no difference in urinary ITC levels between GSTMJ-null and GSTMJ-positive study subjects (P = 0.61) or between subjects with differing GSTPJ genotypes (P = 0.77), but urinary excretion of ITC was significantly higher among GSTTI-positive subjects, relative to GSTTJ-null subjects (P = 0.006). The strength of the association between GSTTJ genotype and urinary total ITC level was highly dependent on the level of cruciferous vegetable consumption (or dietary ITC level) in study subjects. Among subjects in the lowest tertile of cruciferous vegetable intake, there was little evidence of an association between GSTTJ genotype and urinary total ITC level (P 0.67). In contrast, there was a strong and statistically significant association between GS1TJ genotype and urinary total ITC among subjects in the highest tertile of cruciferous vegetable intake (P 0.02), whereas those in the middle tertile of cruciferous vegetable conswnption exhibited an association of intermediate strength (P 0.04). These results suggest the presence of GSTT1 inducers in cruciferous vegetables.