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    Tumour suppressor gene methylation and cervical cell folate concentration are determinants of high-risk human papillomavirus persistence: a nested case control study.

    Flatley, Janet E; Sargent, Alexandra; Kitchener, Henry C; Russell, Jean M; Powers, Hilary J

    BMC cancer. 2014;14:803.

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    Abstract

    BACKGROUND: Persistent infection with one or more high-risk human papillomavirus [HR-HPV] types increases the risk of intraepithelial neoplasia and cervical cancer. A nested case-control study was conducted to investigate the importance of cervical cell folate concentration and tumour suppressor gene methylation as risk factors for HR-HPV persistence. METHODS: Cervical cell samples from 955 women with HR-HPV infection and normal, borderline or mild dyskaryosis were retrieved from the archive of a population-based screening trial. Women were classified as cases or controls, reflecting the presence or absence [respectively] of any HR-HPV infection at a follow-up clinic at least 6 months from baseline. Cervical cell folate concentration and promoter methylation of five tumour suppressor genes were measured in independent samples from cases and controls. RESULTS: A higher cervical cell folate concentration [P = 0.015] was an independent predictor of infection at follow-up, together with infection with HPV-16 or infection with multiple HR-HPV types. Methylation of the tumour suppressor gene DAPK was associated with a 2.64-fold [95% CI, 1.35-5.17] increased likelihood of HPV infection whilst CDH1 methylation was associated with a 0.53-fold [95% CI, 0.331-0.844] likelihood of HR-HPV infection at follow-up. When considering women with normal or abnormal cytology, the predictive effect of higher cervical cell folate was only seen in women with mild cytology [P = 0.021]; similarly the effect of DAPK methylation was seen in women with mild or borderline cytology [P < 0.05]. CONCLUSIONS: Higher cervical cell folate concentration and promoter methylation of the tumour suppressor gene, DAPK, in women with cervical cell dyskaryosis, are associated with increased risk of HR-HPV persistence.

    Bibliographic metadata

    Type of resource:
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    Publication type:
    Published date:
    Journal title:
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    ISSN:
    Place of publication:
    England
    Volume:
    14
    Pagination:
    803
    Digital Object Identifier:
    10.1186/1471-2407-14-803
    Pubmed Identifier:
    25367268
    Pii Identifier:
    1471-2407-14-803
    Access state:
    Active

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    Record metadata

    Manchester eScholar ID:
    uk-ac-man-scw:240270
    Created by:
    Kitchener, Henry
    Created:
    19th November, 2014, 10:30:26
    Last modified by:
    Kitchener, Henry
    Last modified:
    11th April, 2016, 09:04:39

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