Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study.

TitleRole of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study.
Publication TypeJournal Article
Year of Publication2007
AuthorsMitrou, PN, Watson, MA, Loktionov, AS, Cardwell, C, Gunter, MJ, Atkin, WS, Macklin, CP, Cecil, T, D Bishop, T, Primrose, J, Bingham, SA
JournalCarcinogenesis
Volume28
Issue4
Pagination875-82
Date Published2007 Apr
ISSN0143-3334
KeywordsAdenoma, Aged, Alcohol Drinking, Case-Control Studies, Colorectal Neoplasms, Diet, Epoxide Hydrolases, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Mass Screening, Middle Aged, NAD(P)H Dehydrogenase (Quinone), Odds Ratio, Polymorphism, Genetic, Risk Factors, Smoking
Abstract

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.

DOI10.1093/carcin/bgl194
Alternate JournalCarcinogenesis
Citation Key10.1093/carcin/bgl194
PubMed ID17082176
Grant ListG9615910 / / Medical Research Council / United Kingdom
MC_U105630924 / / Medical Research Council / United Kingdom