Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Sistema Enzimático do Citocromo P-450/genética , Glutationa Transferase/genética , Adenoma/etiologia , Neoplasias Colorretais/etiologia , Dieta , Feminino , Genótipo , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Polimorfismo Genético , Sigmoidoscopia , Fumar/efeitos adversos , Inquéritos e Questionários , Reino UnidoRESUMO
NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens.
Assuntos
Adenoma/genética , Consumo de Bebidas Alcoólicas , Neoplasias Colorretais/genética , Epóxido Hidrolases/genética , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo Genético , Fumar , Adenoma/patologia , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Dieta , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
OBJECTIVE: The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps. METHODS: We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening Trial (UKFSS). RESULTS: Investigation of the effect of the MTHFR C677T polymorphism in this large UKFSS study revealed no overall association on adenoma risk (P>0.05). However the MTHFR 1298C allele was linked, for the first time, to high risk adenomas, although in males only (odds ratio (OR) for A/C+C/C compared with A/A 1.55; 95% confidence interval (CI), 1.08-2.22; P=0.018). CONCLUSIONS: In this, the largest study of these polymorphisms in relation to colorectal adenoma, there was no evidence for an interaction with alcohol in combination with the variant forms of MTHFR (P>0.05).