title: IL-4 and TNF-α polymorphisms are associated with risk of multiple superficial tumors or carcinoma in situ development.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, University of Porto, Porto, Portugal. luis14lima @ gmail.com
authors: Luís
authors: L
authors: Lima
authors: Joana
authors: J
authors: Silva
authors: Teresina
authors: T
authors: Amaro
authors: António
authors: A
authors: Morais
authors: Carlos
authors: C
authors: Lopes
authors: Rui
authors: R
authors: Medeiros
authors: Paula A
authors: PA
authors: Videira
authors: Lúcio
authors: L
authors: Santos
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001500:BCG Vaccine / Q000627:therapeutic use; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011174:Portugal; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; C508598:IL4 protein, human; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4