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dc.contributor.authorAcladious, N N
dc.contributor.authorHarrison, Kathryn L
dc.contributor.authorSutton, C J
dc.contributor.authorPovey, Andrew C
dc.contributor.authorMandal, D
dc.contributor.authorKitchener, Henry C
dc.date.accessioned2009-08-24T15:28:43Z
dc.date.available2009-08-24T15:28:43Z
dc.date.issued2004-06
dc.identifier.citationLevels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia. 2004, 93 (3):605-9 Gynecol. Oncol.en
dc.identifier.issn0090-8258
dc.identifier.pmid15196851
dc.identifier.doi10.1016/j.ygyno.2004.03.005
dc.identifier.urihttp://hdl.handle.net/10541/78358
dc.description.abstractOBJECTIVE: To determine whether exposure to methylating agents was a risk factor for treatment failure in women undergoing colposcopic examination. METHODS: Nine hundred fifty-eight women attending for colposcopic examination after abnormal cervical smear test results were recruited into the study cohort. Information on demographic factors, smoking and other risk factors was obtained and a pre-treatment biopsy was taken and stored at -70 degrees C. After follow-up, cases who had treatment failure of cervical intraepithelial neoplasia (CIN) within 2 years following treatment were identified (n = 77) and matched to women with no treatment failure of CIN in this time period (controls, n = 154). DNA was extracted from the pre-treatment biopsies and levels of N7-methyl-deoxyguanosine (N7-MedG), a marker of exposure to methylating agents, were quantified as the ring-opened form of the base damage by a validated immunoslotblot assay. RESULTS: Sufficient DNA for N7-MedG analysis was extracted from 61 subjects corresponding to 20 matched case control pairs. N7-MedG was detected in cervical DNA with levels ranging from non-detected (<0.1 micromol/mol dG) to 4.83 micromol/mol dG. N7-MedG levels were significantly higher in cases (geometric mean 0.99 micromol/mol dG) than controls (0.33 micromol/mol dG; P = 0.01). There were no associations between N7-MedG levels and HPV or smoking status. Log N7-MedG content, after adjustment for HPV status at time of treatment, was found to be significantly associated with increased risk of treatment failure (OR 5.74, 95% CI 1.05-31.23). CONCLUSIONS: The association between pre-treatment levels of DNA damage induced by methylating agents and subsequent treatment failure implicates methylating agent exposure as a causative factor in treatment failure.
dc.language.isoenen
dc.subjectDNA Canceren
dc.subjectUterine Cervical Canceren
dc.subject.meshAdult
dc.subject.meshAlkylating Agents
dc.subject.meshBiopsy
dc.subject.meshCervical Intraepithelial Neoplasia
dc.subject.meshCohort Studies
dc.subject.meshDNA Adducts
dc.subject.meshDNA, Neoplasm
dc.subject.meshDeoxyguanosine
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshProspective Studies
dc.subject.meshRisk Factors
dc.subject.meshSmoking
dc.subject.meshTreatment Outcome
dc.subject.meshUterine Cervical Neoplasms
dc.titleLevels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Genito-Urinary Medicine, Manchester Royal Infirmary, Manchester, UK.en
dc.identifier.journalGynecologic Oncologyen
html.description.abstractOBJECTIVE: To determine whether exposure to methylating agents was a risk factor for treatment failure in women undergoing colposcopic examination. METHODS: Nine hundred fifty-eight women attending for colposcopic examination after abnormal cervical smear test results were recruited into the study cohort. Information on demographic factors, smoking and other risk factors was obtained and a pre-treatment biopsy was taken and stored at -70 degrees C. After follow-up, cases who had treatment failure of cervical intraepithelial neoplasia (CIN) within 2 years following treatment were identified (n = 77) and matched to women with no treatment failure of CIN in this time period (controls, n = 154). DNA was extracted from the pre-treatment biopsies and levels of N7-methyl-deoxyguanosine (N7-MedG), a marker of exposure to methylating agents, were quantified as the ring-opened form of the base damage by a validated immunoslotblot assay. RESULTS: Sufficient DNA for N7-MedG analysis was extracted from 61 subjects corresponding to 20 matched case control pairs. N7-MedG was detected in cervical DNA with levels ranging from non-detected (<0.1 micromol/mol dG) to 4.83 micromol/mol dG. N7-MedG levels were significantly higher in cases (geometric mean 0.99 micromol/mol dG) than controls (0.33 micromol/mol dG; P = 0.01). There were no associations between N7-MedG levels and HPV or smoking status. Log N7-MedG content, after adjustment for HPV status at time of treatment, was found to be significantly associated with increased risk of treatment failure (OR 5.74, 95% CI 1.05-31.23). CONCLUSIONS: The association between pre-treatment levels of DNA damage induced by methylating agents and subsequent treatment failure implicates methylating agent exposure as a causative factor in treatment failure.


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