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

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    Authors
    Billson, H A
    Harrison, Kathryn L
    Lees, Nicholas P
    Hall, C Nicholas
    Margison, Geoffrey P
    Povey, Andrew C
    Affiliation
    Occupational and Environmental Health Research Group, School of Translational Medicine, University of Manchester, Manchester M13 9PL, UK.
    Issue Date
    2009-04
    
    Metadata
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    Abstract
    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 micromol/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/microg 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.
    Citation
    Dietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa. 2009, 30 (4):615-20 Carcinogenesis
    Journal
    Carcinogenesis
    URI
    http://hdl.handle.net/10541/73958
    DOI
    10.1093/carcin/bgp020
    PubMed ID
    19168588
    Type
    Article
    Language
    en
    ISSN
    1460-2180
    ae974a485f413a2113503eed53cd6c53
    10.1093/carcin/bgp020
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Carcinogenesis Group

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