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WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis

  • Jo Richards
    ,
  • Adam Paige
    ,
  • Manuela Zucknick
    ,
  • Szymon Janczar
    ,
  • Jim Paul
    ,
  • Charles A. Mein
  • German Cancer Research Center
    ,
  • Imperial College London
    ,
  • Beatson Institute for Cancer Research
    ,
  • Queen Mary University of London
    ,
  • Cancer Research UK
    ,
  • Leeds Teaching Hospitals NHS Trust
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 818-825

Journal (Volume, Issue Number)

European journal of cancer (Volume 46, Issue 4)

Publication milestones

  • Published - 01/03/2010

Publication status

Published - 01/03/2010

External Publication IDs

  • handle.net: 10547/228936
  • Scopus: 76249122288

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