Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.
dc.contributor.author | Acladious, N N | |
dc.contributor.author | Harrison, Kathryn L | |
dc.contributor.author | Sutton, C J | |
dc.contributor.author | Povey, Andrew C | |
dc.contributor.author | Mandal, D | |
dc.contributor.author | Kitchener, Henry C | |
dc.date.accessioned | 2009-08-24T15:28:43Z | |
dc.date.available | 2009-08-24T15:28:43Z | |
dc.date.issued | 2004-06 | |
dc.identifier.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. | en |
dc.identifier.issn | 0090-8258 | |
dc.identifier.pmid | 15196851 | |
dc.identifier.doi | 10.1016/j.ygyno.2004.03.005 | |
dc.identifier.uri | http://hdl.handle.net/10541/78358 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | DNA Cancer | en |
dc.subject | Uterine Cervical Cancer | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Alkylating Agents | |
dc.subject.mesh | Biopsy | |
dc.subject.mesh | Cervical Intraepithelial Neoplasia | |
dc.subject.mesh | Cohort Studies | |
dc.subject.mesh | DNA Adducts | |
dc.subject.mesh | DNA, Neoplasm | |
dc.subject.mesh | Deoxyguanosine | |
dc.subject.mesh | Female | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Prospective Studies | |
dc.subject.mesh | Risk Factors | |
dc.subject.mesh | Smoking | |
dc.subject.mesh | Treatment Outcome | |
dc.subject.mesh | Uterine Cervical Neoplasms | |
dc.title | Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia. | en |
dc.type | Article | en |
dc.contributor.department | Department of Genito-Urinary Medicine, Manchester Royal Infirmary, Manchester, UK. | en |
dc.identifier.journal | Gynecologic Oncology | en |
html.description.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. |