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Carcinogenesis Advance Access published online on January 23, 2009
Carcinogenesis, 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 Billson1, KL Harrison1, NP Lees1,2,3,4, CN Hall2, GP Margison3 and AC Povey1

1 Occupational and Environmental Health Research Group, University of Manchester
2 Department of General Surgery, Wythenshawe Hospital, Manchester
3 Cancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester
4 Department of Colorectal Surgery, Salford Royal Hospital, Salford

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 to referents (n = 35) free of gastrointestinal neoplasia. The case group consumed significantly more red meat (4.5 vs. 3.4 servings/week, p < 0.05), processed meats, (4.7 vs. 3.2 servings/week, p < 0.05) and % food energy as fat (34.9% vs. 30.7%, p < 0.001). N7-MeG (mean:95%CI) levels were significantly lower in the group that consumed the highest proportion of dietary fibre/1000kcal in comparison with the group with the lowest intake (0.61; 0.35-0.86 vs 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 vs 4.93; 3.95-5.91 fmol/µgDNA, 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.

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


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