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Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder neoplasms 

Authors: Somali Sanyal ab;  Petra J. De Verdier a;  Gunnar Steineck ac;  Per Larsson a;  Erik Oneloumlv a;  Kari Hemminki bd; Rajiv Kumar bd
Affiliations:   a Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
b Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Novum, Sweden
c Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska Academy, Goumlteborg University, Goumlteborg, Sweden
d Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
DOI: 10.1080/02841860600812693
Publication Frequency: 8 issues per year
Published in: journal Acta Oncologica, Volume 46, Issue 1 2007 , pages 31 - 41
Subject: Oncology;
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Abstract

We conducted a follow-up study on 311 patients with urinary bladder neoplasms to investigate the association of polymorphisms in DNA repair and cell growth regulatory genes with the clinical outcomes of this disease. We found that patients carrying the variant allele of XPD (K751Q) polymorphism were at lower risk of death (p = 0.04) than the non-carriers. Patients that were simultaneous carriers of variant alleles from XPD (K751Q) and XPC (K939Q) polymorphisms, showed lower risk of death than the other patients (p = 0.001). The variant allele carriers of MSH6 (G39E) polymorphism showed a higher risk for highly malignant disease (TaG3+T1) than the non-carriers (p = 0.03). The variant allele carriers of XRCC1 (R399Q) polymorphism showed lower risk for recurrence (TaG2; p = 0.05) and death (T2+; p = 0.03) after instillation and radiotherapy than the non-carriers. After radiotherapy, an inverse association of the variant allele of OGG1 (S326C) polymorphism was observed with the risk of death (T2+; p = 0.04). A significant low-risk for stage progression (p = 0.03) was observed in patients carrying the variant allele of H-ras (H27H) polymorphism. Our results are consistent with the notion that the XPD (K751Q) polymorphism either individually or in combination with the XPC (K939Q) polymorphism modulates the risk of death in patients with urinary bladder neoplasms.
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