Specific-mutational patterns of p53 gene in bladder transitional cell carcinoma among a group of Iraqi patients exposed to war environmental hazards

BMC Res Notes. 2012 Aug 28:5:466. doi: 10.1186/1756-0500-5-466.

Abstract

Background: To unfold specific-mutational patterns in TP53 gene due to exposures to war environmental hazards and to detect the association of TP53 gene alteration with the depth of bladder cancer.

Methods: Twenty-nine bladder carcinomas were analyzed for TP53 alterations. PCR-single strand conformational polymorphism analysis, DNA sequencing and immunohistochemical analysis using monoclonal mouse anti-human p53 antibody (Clone DO-7) were employed.

Results: TP53 gene mutations occurred in 37.9% of the cases while TP53 overexpression occurred in 58.6%. Both of them were associated with deep invasive-tumors. Single mutations were seen in 63.6%, whereas only 27.3% have shown double mutations. Four mutations were frameshifted (30.8%); two of them showed insertion A after codon 244. There was no significant association between TP53 mutations and protein overexpression (P>0.05), while a significant association was observed between TP53 alterations and tumors progression (P ≤ 0.01).

Conclusion: The infrequent TP53mutations, especially insertion A and 196 hotspot codon, may represent the specific-mutational patterns in bladder carcinoma among the Iraqi patients who were exposed to war environmental hazards. TP53 alteration associated with bladder cancer progression should be analyzed by both mutational and protein expression analysis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Carcinogens, Environmental / adverse effects*
  • Carcinoma, Transitional Cell / chemically induced*
  • Carcinoma, Transitional Cell / chemistry
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / pathology
  • Cell Transformation, Neoplastic / chemically induced*
  • Cell Transformation, Neoplastic / chemistry
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Codon
  • DNA Mutational Analysis
  • Environmental Exposure*
  • Female
  • Frameshift Mutation
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Iraq
  • Iraq War, 2003-2011*
  • Male
  • Middle Aged
  • Mutagenesis, Insertional
  • Mutation*
  • Neoplasm Invasiveness
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Risk Assessment
  • Risk Factors
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics*
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Carcinogens, Environmental
  • Codon
  • TP53 protein, human
  • Tumor Suppressor Protein p53