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

2.50
Hdl Handle:
http://hdl.handle.net/10541/73958
Title:
Dietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa.
Authors:
Billson, H A; Harrison, Kathryn L; Lees, Nicholas P; Hall, C Nicholas; Margison, Geoffrey P; Povey, Andrew C
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.
Affiliation:
Occupational and Environmental Health Research Group, School of Translational Medicine, University of Manchester, Manchester M13 9PL, UK.
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
Issue Date:
Apr-2009
URI:
http://hdl.handle.net/10541/73958
DOI:
10.1093/carcin/bgp020
PubMed ID:
19168588
Type:
Article
Language:
en
ISSN:
1460-2180
Appears in Collections:
All Paterson Institute for Cancer Research; Carcinogenesis Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBillson, H A-
dc.contributor.authorHarrison, Kathryn L-
dc.contributor.authorLees, Nicholas P-
dc.contributor.authorHall, C Nicholas-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorPovey, Andrew C-
dc.date.accessioned2009-07-15T16:16:04Z-
dc.date.available2009-07-15T16:16:04Z-
dc.date.issued2009-04-
dc.identifier.citationDietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa. 2009, 30 (4):615-20 Carcinogenesisen
dc.identifier.issn1460-2180-
dc.identifier.pmid19168588-
dc.identifier.doi10.1093/carcin/bgp020-
dc.identifier.urihttp://hdl.handle.net/10541/73958-
dc.description.abstractComponents 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.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subjectGastrointestinal Canceren
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAdenoma-
dc.subject.meshAged-
dc.subject.meshCase-Control Studies-
dc.subject.meshCohort Studies-
dc.subject.meshColonic Polyps-
dc.subject.meshColonoscopy-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshDNA-
dc.subject.meshDNA Modification Methylases-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshDiet-
dc.subject.meshFemale-
dc.subject.meshGastrointestinal Neoplasms-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshTumor Suppressor Proteins-
dc.titleDietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa.en
dc.typeArticleen
dc.contributor.departmentOccupational and Environmental Health Research Group, School of Translational Medicine, University of Manchester, Manchester M13 9PL, UK.en
dc.identifier.journalCarcinogenesisen

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