The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

BMC Cancer. 2011 Mar 22;11:101. doi: 10.1186/1471-2407-11-101.

Abstract

Background: In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in XPC, ERCC2 and ERCC5 genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade.

Methods: The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.

Results: Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade.

Conclusion: These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.

MeSH terms

  • Aged
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Case-Control Studies
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Disease Susceptibility
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Endonucleases / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nicotine / pharmacology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Polymorphism, Single Nucleotide / physiology*
  • Tobacco / adverse effects
  • Tobacco / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Xeroderma Pigmentosum Group D Protein / metabolism
  • Xeroderma Pigmentosum Group D Protein / physiology

Substances

  • DNA excision repair protein ERCC-5
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • XPC protein, human
  • Nicotine
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human