title: Identification of patients with developing ulcerative colitis-associated neoplasia by nitrative DNA damage marker 8-nitroguanin expression in rectal mucosa.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors: Susumu
authors: S
authors: Saigusa
authors: Toshimitsu
authors: T
authors: Araki
authors: Koji
authors: K
authors: Tanaka
authors: Kiyoshi
authors: K
authors: Hashimoto
authors: Yoshiki
authors: Y
authors: Okita
authors: Hiroyuki
authors: H
authors: Fujikawa
authors: Yoshinaga
authors: Y
authors: Okugawa
authors: Yuji
authors: Y
authors: Toiyama
authors: Yasuhiro
authors: Y
authors: Inoue
authors: Keiichi
authors: K
authors: Uchida
authors: Yasuhiko
authors: Y
authors: Mohri
authors: Masato
authors: M
authors: Kusunoki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000150:complications* / Q000601:surgery; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000601:surgery; D004249:DNA Damage; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016737:Proctocolectomy, Restorative; D013997:Time Factors; D055815:Young Adult
chemical_list: C095838:8-nitroguanine; D014408:Biomarkers, Tumor; D006147:Guanine