Carcinogenesis Advance Access originally published online on November 1, 2006
Carcinogenesis 2007 28(4):875-882; doi:10.1093/carcin/bgl194
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study
1 Dunn Human Nutrition Unit, MRC/Wellcome Trust Building Hills Road, Cambridge CB2 2XY, UK
2 Department of General Surgery, Norfolk and Norwich Health Care NHS Trust, Norwich NR4 7U4, UK and Dorset County Hospital, Williams Avenue Dorchester, Dorset DT3 5NR, UK
3 Cancer Research UK, 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
*To whom correspondence should be addressed. Tel: +44 1223 252760; Fax: +44 1223 252765; Email: sab{at}mrc-dunn.cam.ac.uk
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.
Abbreviations: CI, confidence interval; NQO1, NADP(H):quinine oxidoreductase 1; OR, odds ratio; PAHs, polycyclic aromatic hydrocarbons; UKFSS, UK Flexible Sigmoidoscopy Screening
Received June 6, 2006; revised September 19, 2006; accepted October 3, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. J. Shrubsole, H. Wu, R. M. Ness, Y. Shyr, W. E. Smalley, and W. Zheng Alcohol Drinking, Cigarette Smoking, and Risk of Colorectal Adenomatous and Hyperplastic Polyps Am. J. Epidemiol., May 1, 2008; 167(9): 1050 - 1058. [Abstract] [Full Text] [PDF]
|
|