Influence of XPD and APE1 DNA repair gene polymorphism on bladder cancer susceptibility in north India

Urology. 2009 Mar;73(3):675-80. doi: 10.1016/j.urology.2008.09.043. Epub 2008 Nov 28.

Abstract

Objectives: To explore the association between xerodema pigmentosum group D (XPD) Asp(312)Asn and Lys(751)Gln and apurinic apyrimidic endonuclease 1 (APE1) Asp(148)Glu gene polymorphism and risk of bladder cancer (BC) susceptibility.

Methods: This hospital-based case-control study included 206 patients with newly diagnosed bladder transitional cell carcinoma and 250 cancer-free controls who had been frequency matched by age, sex, and ethnicity. Polymorphisms in XPD Asp(312)Asn and Lys(751)Gln and APE1 Asp(148)Glu gene using polymerase chain reaction-restriction fragment length polymorphism and amplification refractory mutation system were genotyped.

Results: The XPD Asp(312)Asn AA genotype was associated with an elevated risk of BC (odds ratio [OR] 3.30, P = .001.) The AA genotype was significantly associated with nonmuscle-invasive BC (OR 4.62, corrected P = .003). Both the heterozygous GA and the homozygous AA was associated with a greater risk of low-grade (grade 1) BC (OR 2.51, corrected P = .006 and OR 5.21, corrected P = .003, respectively). The APE1 GG genotype showed a decreased risk of BC (OR 0.27, P = .027.) Haplotype AC (codon 312A-codon 751C) of XPD demonstrated an association with a greater susceptibility to BC (OR 2.16, correct P = .0008).

Conclusions: Reduced DNA repair capacity due to XPD Asp(312)Asn AA genotype might be a risk factor for BC. The AA genotype predisposed to a greater risk at the initial stage and grade of BC. The APE1 148GG genotype conferred a protective association with BC susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Transitional Cell / genetics*
  • Case-Control Studies
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • India
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Urinary Bladder Neoplasms / genetics*
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Xeroderma Pigmentosum Group D Protein
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • ERCC2 protein, human