Analysis of hOGG1 genotype as a prognostic marker for muscle invasive bladder cancer: a novel approach using peptide nucleic acid-mediated, real-time PCR clamping.
OBJECTIVE
DNA damage repair mechanisms are a source of genetic mutation and are believed to play an important role in human cancer. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is involved in the recognition and repair of DNA damage. The value of the hOGG1 genotype as a prognostic indicator for bladder cancer (BC) was assessed using a novel technological approach.


METHODS
The association between genetic polymorphisms of hOGG1 codon 326 and clinicopathologic characteristics of 337 patients with BC was analyzed using peptide nucleic acid (PNA)-mediated real-time PCR clamping.


RESULTS
Tumor grade and size were significantly associated with the hOGG1 codon 326 genotype in non-muscle-invasive bladder cancer (NMIBC). The Cys326Cys polymorphism was significantly associated with progression and cancer specific survival in patients with muscle-invasive bladder cancer (MIBC). Multivariate Cox regression analysis indicated that the hOGG1 Cys326Cys polymorphism is associated with a protective effect on progression and a more dominant survival benefit than the Ser326Ser polymorphism in MIBC (hazard ratio 0.284 and 0.305, respectively).


CONCLUSIONS
Analysis of genotypes and clinical data for 337 BC patients indicates that the hOGG1 genotype may be a useful prognostic genetic marker for MIBC.
Kim
Eun-Jung
EJ
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Yan
Chunri
C
Ha
Yun-Sok
YS
Jeong
Pildu
P
Yi Kim
Isaac
I
Moon
Sung-Kwon
SK
Choi
Yung Hyun
YH
Kim
Wun-Jae
WJ
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009132:Muscles / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020135:Peptide Nucleic Acids / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D020135:Peptide Nucleic Acids; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human