Department of Gastroenterology and Metabolism, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2101-7. doi: 10.1158/1055-9965.EPI-12-0730. Epub 2012 Sep 25.
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.
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.
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.
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.
Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration.
胆汁酸和幽门螺杆菌（H. pylori）是胃黏膜损伤的重要毒性因子。我们研究了胆汁酸在促进日本患者组织学胃炎和胃癌中的作用。
共研究了 767 例患者（452 例男性，平均年龄 51.1 岁）。通过胃镜检查收集胃液，采用酶法检测胆汁酸浓度。通过胃活检评估组织学胃炎的程度，并检查胆汁酸浓度与胃炎评分之间的关系。通过回顾性队列研究检查胃癌的发生情况。通过实时 PCR 评估 RGM-1 细胞中 CDX2/CINC1 的表达。
在 H. pylori 阳性患者中，我们发现胆汁酸浓度与萎缩/肠化生程度之间存在显著正相关（P < 0.01）。然而，我们发现胆汁酸浓度与单核细胞/中性粒细胞浸润的组织学评分之间存在显著负相关（P < 0.01）。胆汁酸浓度高的患者比胆汁酸浓度低的患者更频繁地发生胃癌（P < 0.05）。胆酸处理显著增加了 RGM-1 细胞中 CDX2 的表达。与 H. pylori 共培养显著诱导了 RGM-1 细胞中 CINC1 的表达，而甘氨胆酸处理降低了诱导作用。
胃中的胆汁酸有助于在 H. pylori 阳性患者中无炎症细胞浸润的情况下进行组织学萎缩和肠化生的进展，随后发生癌变。
胆汁酸在无炎症细胞浸润的情况下促进肠化生和胃癌的发生。
