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WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis

Publication Type : Journal Article

Publisher : European Journal of Cancer

Source : European Journal of Cancer, Volume 46, Number 4, p.818-825 (2010)

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Keywords : 80 and over, adolescent, adult, aged, article, cancer survival, female, gene frequency, genomic DNA, genotype, human, human tissue, Humans, Kaplan Meier method, major clinical study, middle aged, Neoplasm Staging, Ovarian Neoplasms, ovary cancer, Oxidoreductases, Polymorphism, priority journal, Prognosis, progression free survival, protein expression, protein p53, Single Nucleotide, single nucleotide polymorphism, Survival Analysis, tumor suppressor gene, Tumor Suppressor Proteins, wwox gene, xeroderma pigmentosum group D protein, Young Adult

Year : 2010

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

Cite this Research Publication : A. J. Wa Paige, Zucknick, Mbh, Janczar, Sa, Paul, Jc, Mein, C. Ad, Taylor, K. Je, Stewart, Me, Gourley, Ce, Richardson, Sb, Perren, Tf, Ganesan, T. Sg, Smyth, J. Fe, Brown, Ra, and Gabra, Ha, “WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis”, European Journal of Cancer, vol. 46, pp. 818-825, 2010.

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