Carcinogenesis Advance Access published online on November 1, 2006
Carcinogenesis, doi:10.1093/carcin/bgl194
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1 Dunn Human Nutrition Unit, MRC/Wellcome Trust Building, Hills Road, Cambridge, CB2 2XY, UK
* To whom correspondence should be addressed. NADP(H):quinine oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolise a number of compounds including polycyclic aromatic hydrocarbons (PAH) 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 Trial (UKFSS). 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.
Received June 6, 2006
Revised September 19, 2006
Accepted October 3, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study
Panagiota N. Mitrou 1, Mark A. Watson 2, Alexandre S. Loktionov 1, Christopher Cardwell 3, Marc J. Gunter 1, Wendy S. Atkin 3, Christopher P. Macklin 4, Tom Cecil 5, D. Timothy Bishop 4, John Primrose 5, and Sheila A. Bingham 1 *
2 Department of General Surgery, Norfolk and Norwich Health Care NHS Trust, Norwich. NR4 7U4, UK; Dorset County Hospital, Williams Avenue, Dorchester, Dorset DT3 5NR, UK
3 Cancer Research U.K., St Mark's Hospital, Northwick Park, Harrow, HA1 3UJ, UK
4 Cancer Research UK Genetic Epidemiology Section, St James's University Hospital, Leeds, LS9 7TF, UK
5 Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, UK
Sheila A. Bingham, E-mail: sab{at}mrc-dunn.cam.ac.uk
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