Tissue hOGG1 genotype predicts bladder cancer prognosis: a novel approach using a peptide nucleic acid clamping method

Ann Surg Oncol. 2011 Jun;18(6):1775-81. doi: 10.1245/s10434-010-1500-7. Epub 2010 Dec 24.

Abstract

Background: Tissue genotyping is a more useful approach than using blood genomic DNA, because the tumor tissues can reflect the effects of somatic mutations in cancer. We investigated the value of the human oxoguanine glycosylase (hOGG1) genotype determined in tumor tissues as a prognostic indicator for bladder cancer (BC) using a novel technological approach.

Methods: A total of 335 DNA samples from patients with primary BC were analyzed by peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction (PCR) clamping to characterize the association between genetic polymorphisms within hOGG1 codon 326 and the clinicopathological characteristics of primary BC patients.

Results: Tumor stage and number were significantly associated with the hOGG1 codon 326 genotype in nonmuscle invasive bladder cancer (NMIBC) patients. Compared with Cys326Ser and Ser326Ser, the Cys326Cys genotype had a greater progression-free survival benefit in patients with muscle invasive bladder cancer (MIBC). Univariate and multivariate Cox regression analyses indicated that the hOGG1 Cys326Cys genotype has a protective effect against progression in MIBC (hazard ratio, 0.360 and 0.314, respectively).

Conclusions: The hOGG1 tissue genotype is associated with aggressive clinicopathological features in NMIBC and with progression in patients with MIBC. Results suggest that the hOGG1 tissue genotype represents a promising marker for assessing BC prognosis in the clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy
  • Codon / genetics
  • DNA Glycosylases / genetics*
  • Humans
  • Muscle Neoplasms / genetics*
  • Muscle Neoplasms / pathology
  • Muscle Neoplasms / therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Peptide Nucleic Acids*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Risk Factors
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy

Substances

  • Codon
  • Peptide Nucleic Acids
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human