IL-4 and TNF-α polymorphisms are associated with risk of multiple superficial tumors or carcinoma in situ development

Urol Int. 2011;87(4):457-63. doi: 10.1159/000331882. Epub 2011 Nov 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • BCG Vaccine / therapeutic use
  • Carcinoma in Situ / drug therapy
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / immunology
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology
  • Chi-Square Distribution
  • Disease-Free Survival
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-4 / genetics*
  • Kaplan-Meier Estimate
  • Neoplasms, Multiple Primary / drug therapy
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / immunology
  • Neoplasms, Multiple Primary / mortality
  • Neoplasms, Multiple Primary / pathology
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Portugal
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • BCG Vaccine
  • IL4 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-4