Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk

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Abstract
Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. ITCs down‐regulate cytochrome P‐450 biotransformation enzyme levels, activate Phase II detoxifying enzymes and induce apoptosis. On the other hand, ITCs also serve as a substrate for GSTs. Experimental evidences suggest that ITCs have anticarcinogenic effect on bladder cancer. Therefore, we evaluated dietary intake of ITCs, GSTM1, GSTT1 and NAT2 polymorphisms, and bladder cancer risk in a case–control study. There were 697 newly diagnosed bladder cancer cases identified from The University of Texas M. D. Anderson Cancer Center and 708 healthy controls matched to cases by age (±5), gender and ethnicity. Participants underwent an in‐person interview, in which epidemiologic and food frequency questionnaires were administered to collect demographic and dietary intake data. Median ITC intake per day was statistically significantly lower in cases than in controls (0.23 vs. 0.33, p < 0.001). High ITC intake was associated with 29% decreased risk of bladder cancer [Odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.57, 0.89]. The protective effect was more evident in older individuals (≥64‐years‐old), men, ever smokers and heavy smokers in stratified analysis. Compared with NAT2 rapid acetylator, NAT2 slow acetylator had an increased risk of bladder cancer in Caucasians (OR = 1.31, 95% CI = 1.02, 1.69). There was no main effect associated with the GSTM1 or GSTT1 genotypes. The protective effect of ITCs against bladder cancer was not modified by GSTM1, GSTT1 or NAT2 genotypes. This is the first epidemiological report that ITCs from cruciferous vegetable consumption protect against bladder cancer.