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

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    Authors
    Acladious, N N
    Harrison, Kathryn L
    Sutton, C J
    Povey, Andrew C
    Mandal, D
    Kitchener, Henry C
    Affiliation
    Department of Genito-Urinary Medicine, Manchester Royal Infirmary, Manchester, UK.
    Issue Date
    2004-06
    
    Metadata
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    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.
    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
    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
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ygyno.2004.03.005
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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