title: Bile acid promotes intestinal metaplasia and gastric carcinogenesis.
abstract: BACKGROUND
  Bile acid and Helicobacter pylori (H. pylori) are important toxic factors for gastric mucosal injury. We examined the role of bile acid in promoting histologic gastritis and gastric carcinoma in Japanese patients.
  
  
  METHODS
  A total of 767 patients (452 men, mean age 51.1 years) were studied. Gastric juice was collected by gastro-endoscopic examination, and the bile acid concentration was examined by enzymatic method. The grade of histologic gastritis was evaluated by gastric biopsies, and the relationship between the bile acid concentration and the gastritis score was examined. The occurrence of gastric cancer was examined by a retrospective cohort study. CDX2/CINC1 expression in RGM-1 cells was evaluated by real-time PCR.
  
  
  RESULTS
  In H. pylori-positive patients, we found significant positive correlation between the bile acid concentration and the grades of atrophy/intestinal metaplasia (P < 0.01). However, we found significant negative associations between the bile acid concentrations and the histologic scores of mononuclear cell/neutrophil infiltrations (P < 0.01). Patients with a high concentration of bile acid developed gastric cancer more frequently than those with a low concentration (P < 0.05). Cholic acid treatment significantly increased CDX2 expression in RGM-1 cells. CINC1 expression in RGM-1 cell was significantly induced by coculture with H. pylori, and the induction was reduced by glycochenodeoxycholic acid treatment.
  
  
  CONCLUSIONS
  The bile acid in gastric juice contributes to the progression of histologic atrophy and intestinal metaplasia without inflammatory cell infiltration, followed by carcinogenesis in H. pylori-positive patients.
  
  
  CONCLUSIONS
  Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration.
authors.affiliation: Department of Gastroenterology and Metabolism, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Masana
authors.initials: M
authors.lastname: Tatsugami
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D012189:Retrospective Studies; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D001647:Bile Acids and Salts