GST Polymorphism and Excretion of Heterocyclic Aromatic Amine and Isothiocyanate Metabolites after Brassica Consumption

Brassica vegetable intake has been associated with decreased risk and well-done meat intake has been associated with increased risk of cancers at multiple organ sites in epidemiologic studies. Experimental studies suggest a role of modulation of phase I and phase II metabolizing enzymes as one mechanism for these associations. Heterocyclic aromatic amines (HAAs) are carcinogens formed in meat that has been cooked to well-done and at high temperatures. Phase I metabolizing enzymes catalyze the activation of HAAs, and phase II metabolizing enzymes serve to detoxify the active carcinogens. The glutathione S-transferase (GSTs) are a family of phase II metabolizing enzymes that are induced by, and act to conjugate, isothiocyanates (ITCs), phytochemicals found in Brassica vegetables. This review summarizes the results of feeding studies in humans that examine effects of polymorphisms in GSTs on ITC metabolite excretion, reviews the evidence for modulation of HAA mutagenicity by ITCs, and discusses the need for feeding studies examining potential interactions among polymorphic genes encoding phase I and phase II metabolizing enzymes, meat intake, and Brassica intake to elucidate their role in cancer etiology