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Carcinogenesis Advance Access originally published online on January 23, 2009
Carcinogenesis 2009 30(4):615-620; doi:10.1093/carcin/bgp020
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa

H. A. Billson1, K. L. Harrison1, N. P. Lees1,2,3,4, C. N. Hall2, G. P. Margison3 and A. C. Povey1,*

1 Occupational and Environmental Health Research Group, School of Translational Medicine, University of Manchester, Manchester M13 9PL, UK
2 Department of General Surgery, Wythenshawe Hospital, Manchester M23 9LT, UK
3 Cancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK
4 Department of Colorectal Surgery, Salford Royal Hospital, Salford M6 8HD, UK

* To whom correspondence should be addressed. Tel: +44 161 275 5232; Fax: +44 161 275 5595; Email: apovey{at}manchester.ac.uk

Components of human diets may influence the incidence of colorectal adenomas, by modifying exposure or susceptibility to DNA-damaging alkylating agents. To examine this hypothesis, a food frequency questionnaire was used to assess the diet of patients recruited for a case–referent study where biopsies of normal colorectal mucosa were collected during colonoscopy and subsequently analysed for DNA N7-methylguanine (N7-MeG) levels, as an indicator of exposure, and activity of the DNA repair protein O6-alkylguanine DNA-alkyltransferase (MGMT), as an indicator of potential susceptibility. Cases with histologically proven colorectal adenomas (n = 38) were compared with referents (n = 35) free of gastrointestinal neoplasia. The case group consumed significantly more red meat (4.5 versus 3.4 servings/week, P < 0.05), processed meats, (4.7 versus 3.2 servings/week, P < 0.05) and % food energy as fat (34.9 versus 30.7%, P < 0.001). N7-MeG [mean: 95% confidence interval (CI)] levels were significantly lower in the group that consumed the highest proportion of dietary fibre/1000 kcal in comparison with the group with the lowest intake (0.61; 0.35–0.86 versus 1.88; 0.88–2.64 µmol/mol dG, P < 0.05). N7-MeG levels were also inversely associated with folate consumption (P < 0.05). MGMT activity (mean; 95% CI) was significantly higher in the group with the lowest consumption of vegetables than in the group with the greatest vegetable consumption (7.02; 5.70–8.33 versus 4.93; 3.95–5.91 fmol/µg DNA, P < 0.05). Our results are consistent with the hypothesis that dietary factors may modify exposure or susceptibility, respectively, to DNA damage by alkylating agents.

Abbreviations: CRC, colorectal cancer; CI, confidence interval; FFQ, food frequency questionnaire; MGMT, O6-alkylguanine DNA-alkyltransferase; N7-MeG, DNA N7-methylguanine; O6-MeG, O6-methylguanine

Received August 8, 2008; revised December 29, 2008; accepted January 13, 2009.


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