Bile Acid Promotes Intestinal Metaplasia and Gastric Carcinogenesis
Bile Acid Promotes Intestinal Metaplasia and Gastric Carcinogenesis
复制标题
DOI：
10.1158/1055-9965.epi-12-0730
复制
发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
--
作者：
Tatsugami, Masana;Ito, Masanori;Chayama, Kazuaki
背景：胆汁酸与幽门螺杆菌（H。pylori）是胃粘膜损伤的重要毒性因子。我们研究了胆汁酸的作用，促进组织学胃炎和胃癌在日本patients.Methods：共767例（452名男性，平均年龄51.1岁）进行了研究。胃镜下取胃液，酶法测定胆汁酸浓度。通过胃活检评估组织学胃炎的分级，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率。实时荧光定量PCR检测RGM-1细胞中CDX 2/CINC 1的表达。pylori阳性患者胆汁酸浓度与萎缩/肠化分级呈显著正相关（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呈显著负相关（P < 0.01）。胆汁酸浓度高的患者发生胃癌的概率高于胆汁酸浓度低的患者（P < 0.05）。胆酸处理显著增加RGM-1细胞中CDX 2的表达。与H.结论：胃液中胆汁酸可促进H. pylori胃黏膜组织萎缩和肠上皮化生的发生，但不伴有炎性细胞浸润，进而促进H. pylori胃黏膜癌变。影响：胆汁酸促进肠上皮化生和胃癌发生，而无炎性细胞浸润。癌症流行病学生物标志物Prev; 21（11）; 2101-7。（C）2012年AACR。
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.Conclusion: 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.Impact: Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration. Cancer Epidemiol Biomarkers Prev; 21(11); 2101-7. (C)2012 AACR.