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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 proteinO  6-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 &lt; 0.05), processed meats, (4.7 versus 3.2 servings/week,P &lt; 0.05) and % food energy as fat (34.9 versus 30.7%,P &lt; 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 &lt; 0.05). N7-MeG levels were also inversely associated with folate consumption (P &lt; 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 &lt; 0.05). Our results are consistent with the hypothesis that dietary factors may modify exposure or susceptibility, respectively, to DNA damage by alkylating agents.

carcinogenesis

Dietary variables associated with DNA N7-methylguanine levels and               O  6              -alkylguanine DNA-alkyltransferase activity in human colorectal mucosa