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    WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis.

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    Authors
    Paige, Adam J.W.
    Zucknick, Manuela
    Janczar, Szymon
    Paul, Jim
    Mein, Charles A.
    Taylor, Karen J.
    Stewart, Moira
    Gourley, Charlie
    Richardson, Sylvia
    Perren, Timothy
    Ganesan, Trivadi S.
    Smyth, John F.
    Brown, Robert
    Gabra, Hani
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    Affiliation
    Imperial College London
    Issue Date
    2010-03
    
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    Abstract
    WWOX is a bona fide tumour suppressor, with hypomorphic and knockout mouse models exhibiting increased tumour susceptibility. In ovarian cancer cells WWOX transfection abolishes tumourigenicity, suppresses tumour cell adhesion to extracellular matrix and induces apoptosis in non-adherent cells. One-third of ovarian tumours show loss of WWOX expression, and this loss significantly associates with clear cell and mucinous histology, advanced stage, low progesterone receptor expression and poor survival, suggesting that WWOX status affects ovarian cancer progression and prognosis. Genetic variation in other tumour suppressors (e.g. p53 and XPD) is reported to modify cancer progression/outcome, and single nucleotide polymorphisms (SNPs) within the WWOX gene are reported to associate with prostate cancer risk. We previously identified polymorphic variants within WWOX, some of which have potential to affect its expression. We therefore examined a cancer modifier role for these WWOX variants. Eight SNPs, based upon location, frequency and potential to affect WWOX expression, were genotyped in 554 ovarian cancer patients (CGP samples), and associations with pathological and survival data were examined. The CGP samples demonstrated significant associations after Bonferroni correction between Isnp1 and both tumour grade (p(corr)=0.033) and histology (p(corr)=0.046), Isnp8 and tumour grade (p(corr)=0.032) and T1497G and progression-free survival (p(corr)=0.037). None of these positive associations were confirmed in an independent ovarian cancer population (Scotroc1 samples, n=863). While these results may suggest that the associations are false positives, differences between the two populations cannot be excluded, and thus highlight the challenges in validation studies.
    Citation
    Paige, A.J.W. et al (2010) 'WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis' Eur. J. Cancer 46 (4):818-825
    Publisher
    Elsevier
    Journal
    European journal of cancer (Oxford, England : 1990)
    URI
    http://hdl.handle.net/10547/228936
    DOI
    10.1016/j.ejca.2009.12.021
    PubMed ID
    20074932
    Additional Links
    http://www.ncbi.nlm.nih.gov/pubmed/20074932
    http://www.sciencedirect.com/science/article/pii/S0959804909009332
    Type
    Article
    Language
    en
    ISSN
    1879-0852
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2009.12.021
    Scopus Count
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    Cell and Cryobiology Research Group

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