IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ DevelopmentLima L.a–c · Silva J.d · Amaro T.e · Morais A.f · Lopes C.a, g · Medeiros R.d, g, h · Videira P.A.i · Santos L.a, h, j
aExperimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, bICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, cNucleo de Investigação em Farmácia, Centro de Estudos em Saúde e Ambiente, School of Allied Health Sciences, Polytechnic Institute of Porto, dMolecular Oncology Group, Portuguese Institute of Oncology, eDepartment of Pathology and fDepartment of Urology, Portuguese Institute of Oncology, gDepartment of Pathology and Molecular Immunology, ICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, and hHealth Faculty of University Fernando Pessoa, Porto; iCEDOC, Department of Immunology, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisbon; jDepartment of Surgical Oncology, Portuguese Institute of Oncology, Porto, Portugal
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Introduction: This study evaluates the influence of clinicopathological characteristics, bacillus Calmette-Guérin (BCG) therapeutic schedule [maintenance (mBCG) or induction (iBCG)], and TNF-α and IL-4 polymorphisms on the outcome of non-muscle-invasive bladder cancer patients treated with BCG. Material and Methods: DNA was extracted from 125 bladder cancer patients treated with BCG; TNF-308G/A and IL4-590C/T polymorphisms were genotyped. Results: The TNF-308A allele carriers had an increased risk of developing multiple tumors (OR: 2.80, p = 0.031). However, IL4-590 T carriers also had an increased risk of developing multiple and carcinoma in situ tumors (OR: 2.52, p = 0.033). For these polymorphisms, no association was found with BCG treatment outcome. When treated with iBCG, patients with multiple tumors had shorter recurrence-free survival (RFS) compared with those with a single tumor (p = 0.004); nevertheless, patients with multifocal tumors have improved RFS when treated with mBCG. Conclusions: Overall, the results suggest that multiple tumors and/or carcinoma in situ development are associated with the IL4-590C/T and TNF-308G/A polymorphisms, and emphasize the effectiveness of the mBCG schedule.
© 2011 S. Karger AG, Basel
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