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Identification of Patients With Developing Ulcerative Colitisassociated Neoplasia by Nitrative DNA Damage Marker 8-Nitroguanin Expression in Rectal Mucosa

Saigusa, Susumu MD, PhD; Araki, Toshimitsu MD, PhD; Tanaka, Koji MD, PhD; Hashimoto, Kiyoshi MD; Okita, Yoshiki MD, PhD; Fujikawa, Hiroyuki MD, PhD; Okugawa, Yoshinaga MD, PhD; Toiyama, Yuji MD, PhD; Inoue, Yasuhiro MD, PhD; Uchida, Keiichi MD, PhD; Mohri, Yasuhiko MD, PhD; Kusunoki, Masato MD, PhD

Journal of Clinical Gastroenterology:
doi: 10.1097/MCG.0b013e31828f51e1
ONLINE ARTICLE: Original Articles
Abstract

Goal: To clarify whether the expression of nitrative and oxidative DNA damage markers in the rectal mucosa of patients with ulcerative colitis (UC) could be used to predict UC-associated neoplasia.

Background: A longer duration of UC can increase the risk of developing UC-associated cancer (UCAC). Effective diagnostic markers are being sought to provide more selective screening and treatment strategies for patients with long-standing UC.

Study: A total of 141 patients with UC who underwent a proctocolectomy were enrolled in this study. The expression of 8-nitroguanine (8-NG), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and inducible nitric oxide synthase (iNOS) in the rectal mucosa were evaluated using immunohistochemistry (IHC) and assessed relative to the pathogenesis of UC-associated neoplasia.

Results: Eighteen patients (12.8%) had UC-associated neoplasia including low-grade or high-grade dysplasia and UCAC. IHC scores of 8-NG in UC-associated neoplasia group was significantly higher than in non-neoplasia group (P<0.0001). In contrast, IHC score of 8-oxodG in non-neoplasia group was significantly decreased compared with UC-associated neoplasia group (P=0.0028). In logistic regression analysis, duration of disease >8 years, high IHC scores of 8-NG, and low 8-oxodG in the rectal mucosa were significantly associated with the development of UC-associated neoplasia (P<0.01). The expression of 8-NG was more frequently observed in patients with UCAC than in patients with sporadic colorectal cancer (P<0.01).

Conclusion: These results suggest that evaluating the expression levels of 8-NG in the rectal mucosa may be a useful biomarker for detecting patients with UC-associated neoplasia.

Author Information

Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan

The authors declare that they have nothing to disclose.

Reprints: Susumu Saigusa, MD, PhD, Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan (e-mail: saigusa@clin.medic.mie-u.ac.jp).

Received August 21, 2012

Accepted February 26, 2013

© 2013 by Lippincott Williams & Wilkins