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

Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS study
Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS study
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.
care, sigmoidoscopy, carcinogenesis, smoking, nad(p)h-quinone oxidoreductase, quinone oxidoreductase 1, activation, high-risk, microsomal epoxide hydrolase, susceptibility, carriers, time, colon-cancer, lung-cancer, population, trial, risk, gene, candidate, cigarette-smoking, flexible sigmoidoscopy, polymorphisms, multicenter randomized trial, risk-factors, variant
0143-3334
875-882
Mitrou, Panagiota N.
af30d670-36ed-44ef-8f7b-89bcbca04616
Watson, Mark A.
48aea4a8-00cb-441b-b090-b4350b00a98d
Loktionov, Alexandre S.
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Cardwell, Christopher
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Gunter, Marc J.
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Atkin, Wendy S.
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Macklin, Christopher P.
be3a7fe0-c3ed-421e-b50a-02c6e023a53f
Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Bishop, D. Timothy
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Primrose, John
d85f3b28-24c6-475f-955b-ec457a3f9185
Bingham, Sheila A.
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Mitrou, Panagiota N.
af30d670-36ed-44ef-8f7b-89bcbca04616
Watson, Mark A.
48aea4a8-00cb-441b-b090-b4350b00a98d
Loktionov, Alexandre S.
bef20815-afc2-4a37-bf24-b435d161552f
Cardwell, Christopher
11595aee-491e-4da2-a906-65399fa10732
Gunter, Marc J.
8dde34f9-71b3-4f43-a3bb-f53e0c135154
Atkin, Wendy S.
9bd5a0aa-dbcb-4709-8ec1-a65f110062a7
Macklin, Christopher P.
be3a7fe0-c3ed-421e-b50a-02c6e023a53f
Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Bishop, D. Timothy
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Primrose, John
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Bingham, Sheila A.
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Mitrou, Panagiota N., Watson, Mark A., Loktionov, Alexandre S., Cardwell, Christopher, Gunter, Marc J., Atkin, Wendy S., Macklin, Christopher P., Cecil, Tom, Bishop, D. Timothy, Primrose, John and Bingham, Sheila A. (2007) Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS study. Carcinogenesis, 28 (4), 875-882. (doi:10.1093/carcin/bgl194).

Record type: Article

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.

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More information

Published date: 2007
Keywords: care, sigmoidoscopy, carcinogenesis, smoking, nad(p)h-quinone oxidoreductase, quinone oxidoreductase 1, activation, high-risk, microsomal epoxide hydrolase, susceptibility, carriers, time, colon-cancer, lung-cancer, population, trial, risk, gene, candidate, cigarette-smoking, flexible sigmoidoscopy, polymorphisms, multicenter randomized trial, risk-factors, variant

Identifiers

Local EPrints ID: 62850
URI: http://eprints.soton.ac.uk/id/eprint/62850
ISSN: 0143-3334
PURE UUID: c8ca94b0-72f7-4c28-a01f-3256217e6abc
ORCID for John Primrose: ORCID iD orcid.org/0000-0002-2069-7605

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Date deposited: 11 Sep 2008
Last modified: 16 Mar 2024 02:47

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Contributors

Author: Panagiota N. Mitrou
Author: Mark A. Watson
Author: Alexandre S. Loktionov
Author: Christopher Cardwell
Author: Marc J. Gunter
Author: Wendy S. Atkin
Author: Christopher P. Macklin
Author: Tom Cecil
Author: D. Timothy Bishop
Author: John Primrose ORCID iD
Author: Sheila A. Bingham

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