Original article 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 Eun-Jung Kim, Ph.D. a,b , Chunri Yan, B.Sc. a,b , Yun-Sok Ha, M.D., Ph.D. a , Pildu Jeong, Ph.D. a , Isaac Yi Kim, M.D., Ph.D. c , Sung-Kwon Moon, Ph.D. d , Yung Hyun Choi, Ph.D. e , Wun-Jae Kim, M.D., Ph.D. a,b, * a Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea b BK21 Chungbuk Biomedical Science Center, School of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea c Section of Urologic Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA d Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk, South Korea e Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Busan, South Korea Received 20 May 2010; received in revised form 14 July 2010; accepted 14 July 2010 Abstract 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. Materials and 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. Crown Copyright © 2012 Published by Elsevier Inc. All rights reserved. Keywords: Urinary bladder neoplasms; DNA damage repair mechanisms; hOGG1; Biological tumor markers; Prognosis; PNA 1. Introduction Bladder cancer (BC) can be of two types, non-muscle- invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on pathological findings. Recurrence and progression are the most serious risks fol- lowing treatment of NMIBC, whereas local invasion and distant metastasis are life-threatening issues in patients with MIBC. Numerous factors are involved in cancer recurrence, progression, and patient survival, including both environ- mental and hereditary factors [1]. Many agents can attack cellular DNA, thereby initiating tumorigenesis and promot- ing disease recurrence, progression, and metastasis [2]. Hu- mans have acquired DNA repair mechanisms to repair DNA that is damaged by these agents [3,4]. DNA lesions that contain the mutagenic base 8-oxogua- nine are repaired by base excision repair [5]. Human 8-ox- oguanine DNA glycosylase 1 (hOGG1) encodes a DNA glycosylase that catalyzes the excision of 8-oxoguanine from oxidatively damaged DNA [6,7]. A Ser326Cys poly- morphism of hOGG1 has been identified in bladder, lung, and esophageal cancers [8 –10]. * Corresponding author. Tel.: +82-43-269-6371; fax: +82-43-269- 6144. E-mail address: wjkim@chungbuk.ac.kr (W.-J. Kim). Urologic Oncology: Seminars and Original Investigations 30 (2012) 673– 679 1078-1439/$ – see front matter Crown Copyright © 2012 Published by Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2010.07.008