Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78358
Title:
Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.
Authors:
Acladious, N N; Harrison, Kathryn L; Sutton, C J; Povey, Andrew C; Mandal, D; Kitchener, Henry C
Abstract:
OBJECTIVE: 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.
Affiliation:
Department of Genito-Urinary Medicine, Manchester Royal Infirmary, Manchester, UK.
Citation:
Levels 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.
Journal:
Gynecologic Oncology
Issue Date:
Jun-2004
URI:
http://hdl.handle.net/10541/78358
DOI:
10.1016/j.ygyno.2004.03.005
PubMed ID:
15196851
Type:
Article
Language:
en
ISSN:
0090-8258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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

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