2.50
Hdl Handle:
http://hdl.handle.net/10547/228936
Title:
WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis.
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
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.
Affiliation:
Imperial College London
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)
Issue Date:
Mar-2010
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
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorPaige, Adam J.W.en_GB
dc.contributor.authorZucknick, Manuelaen_GB
dc.contributor.authorJanczar, Szymonen_GB
dc.contributor.authorPaul, Jimen_GB
dc.contributor.authorMein, Charles A.en_GB
dc.contributor.authorTaylor, Karen J.en_GB
dc.contributor.authorStewart, Moiraen_GB
dc.contributor.authorGourley, Charlieen_GB
dc.contributor.authorRichardson, Sylviaen_GB
dc.contributor.authorPerren, Timothyen_GB
dc.contributor.authorGanesan, Trivadi S.en_GB
dc.contributor.authorSmyth, John F.en_GB
dc.contributor.authorBrown, Roberten_GB
dc.contributor.authorGabra, Hanien_GB
dc.date.accessioned2012-06-14T11:44:16Zen
dc.date.available2012-06-14T11:44:16Zen
dc.date.issued2010-03en
dc.identifier.citationPaige, A.J.W. et al (2010) 'WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis' Eur. J. Cancer 46 (4):818-825en_GB
dc.identifier.issn1879-0852en
dc.identifier.pmid20074932en
dc.identifier.doi10.1016/j.ejca.2009.12.021en
dc.identifier.urihttp://hdl.handle.net/10547/228936en
dc.description.abstractWWOX 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.en_GB
dc.language.isoenen
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/20074932en_GB
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0959804909009332en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshFemaleen
dc.subject.meshGene Frequencyen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMiddle Ageden
dc.subject.meshNeoplasm Stagingen
dc.subject.meshOvarian Neoplasmsen
dc.subject.meshOxidoreductasesen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshPrognosisen
dc.subject.meshSurvival Analysisen
dc.subject.meshTumor Suppressor Proteinsen
dc.subject.meshYoung Adulten
dc.titleWWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis.en
dc.typeArticleen
dc.contributor.departmentImperial College Londonen_GB
dc.identifier.journalEuropean journal of cancer (Oxford, England : 1990)en_GB

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