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

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.