Colorectal cancer and genetic polymorphisms ofCYP1A1,GSTM1andGSTT1: A case-control study in the Grampian region of Scotland


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Abstract

Cytochrome P-450 CYP1A1 is involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) that are derived from meat intake and tobacco smoking. Expression of theCYP1A1gene is induced by compounds present in cruciferous vegetables. The glutathioneS-transferases play a central role in the detoxification of carcinogens, including PAHs. We investigated the association between colorectal cancer and three variants (CYP1A1*2A, CYP1A1*2C, CYP1A1*4) of theCYP1A1gene, and homozygosity for the null deletion of theGSTM1andGSTT1genes, and the joint effects of these genotypes and smoking, meat intake and intake of green leafy vegetables in a population-based study of 264 cases and 408 controls in Northeast Scotland. There was an inverse association with theCYP1A1*4(m4) variant (OR 0.3, 95% CI 0.13–0.70). The OR for theCYP1A1*2C(m2) variant was 1.3 (95% CI 0.59–2.91), which is similar to a combined estimate for previous studies (OR 1.2, 95% CI 0.95–1.41). We observed no association with theCYP1A1*2A(m1) variant, or theGSTM1andGSTT1polymorphisms. Significant interactions between all 3CYP1A1variants and meat intake, and between the m1 and m2 variants and intake of green leafy vegetables, were observed. There was no evidence of interaction betweenCYP1A1and smoking, and no evidence of interaction between theGSTM1orGSTT1polymorphisms and smoking, meat intake, green leafy vegetable intake,CYP1A1variants or each other.

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