Bile Reflux is an Independent Risk Factor for Precancerous Gastric Lesions and Gastric Cancer: An Observational Cross-sectional Study

Overview

Journal J Dig Dis

Specialty Gastroenterology

Date 2021 Apr 1

PMID 33793080

Citations 21

Authors

Lu Yao Zhang

Jian Zhang

Dan Li

Yuan Liu

Dong Ling Zhang

Cai Fang Liu

Na Wang

Si Ran Wu

Wen Quan Lu

Jing Zhi Guo

Yong Quan Shi

Affiliations

Soon will be listed here.

Abstract

Objective: To identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer (GC).

Methods: A multicenter, cross-sectional and observational study was conducted in five centers in China from June to October 2019, 1162 patients were recruited and divided into the chronic gastritis (CG), the precancerous lesion (low-grade intraepithelial neoplasia and intestinal metaplasia), and GC groups (including high-grade intraepithelial neoplasia). All participants underwent detailed interviews, endoscopy and biopsy, and completed questionnaires. Odds ratio and 95% confidence interval were calculated with multivariate logistic regression models with or without adjustment for Helicobacter pylori infection.

Results: We recruited 668 patients with CG, 411 with precancerous lesions and 83 with GC. By comparing the CG and precancerous lesion groups, independent risk factors for cancerous gastric lesions were the grade of bile reflux, patient's age, dietary habits and family history of GC. Similar results were obtained when comparing the CG and GC groups. In addition, bile reflux was confirmed as an independent risk factor for progression from precancerous lesions to cancer.

Conclusions: Bile reflux on endoscopy as well as age, dietary habits and a family history of GC were independent risk factors for the development of precancerous gastric lesions and GC.

Citing Articles

Analysis of Risk Factors for Gastric Cancer and Precancerous Lesions: A Case-Control Study.

Gao M, Li S, Zhu X, Zhang L, Chen M, Shi Y J Dig Dis. 2025; 25(11-12):674-684.

PMID: 39865979 PMC: 11877994. DOI: 10.1111/1751-2980.13326.

Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review.

Kuang W, Xu J, Xu F, Huang W, Majid M, Shi H Front Cell Dev Biol. 2024; 12:1513426.

PMID: 39720008 PMC: 11666564. DOI: 10.3389/fcell.2024.1513426.

Development and validation of a nomogram for obesity and related factors to detect gastric precancerous lesions in the Chinese population: a retrospective cohort study.

Shi C, Tao R, Wang W, Tang J, Dou Z, Yuan X Front Oncol. 2024; 14:1419845.

PMID: 39634264 PMC: 11614725. DOI: 10.3389/fonc.2024.1419845.

Efficacy of ursodeoxycholic acid for bile reflux after distal gastrectomy in patients with gastric cancer: a secondary analysis of the PEGASUS-D randomized clinical trial.

Jang D, Park Y, Yoo M, Hwang S, Ryu S, Kwon O Int J Surg. 2024; 110(12):7824-7831.

PMID: 39422533 PMC: 11634197. DOI: 10.1097/JS9.0000000000002127.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

Balonov I, Mattis M, Jarmusch S, Koletzko B, Heinrich K, Neumann J J Cancer Res Clin Oncol. 2024; 150(7):331.

PMID: 38951269 PMC: 11217139. DOI: 10.1007/s00432-024-05857-5.

References

Yan S, Li B, Bai Z, Wu J, Xie D, Ma Y . Clinical epidemiology of gastric cancer in Hehuang valley of China: a 10-year epidemiological study of gastric cancer. World J Gastroenterol. 2014; 20(30):10486-94. PMC: 4130857. DOI: 10.3748/wjg.v20.i30.10486. View

Lage J, Uedo N, Dinis-Ribeiro M, Yao K . Surveillance of patients with gastric precancerous conditions. Best Pract Res Clin Gastroenterol. 2016; 30(6):913-922. DOI: 10.1016/j.bpg.2016.09.004. View

Matsuhisa T, Arakawa T, Watanabe T, Tokutomi T, Sakurai K, Okamura S . Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases. Dig Endosc. 2013; 25(5):519-25. DOI: 10.1111/den.12030. View

Wu Y, Chiu C, Hsueh C, Hsueh C . The role of bile acids in cellular invasiveness of gastric cancer. Cancer Cell Int. 2018; 18:75. PMC: 5963058. DOI: 10.1186/s12935-018-0569-0. View

Duan F, Song C, Zhang J, Wang P, Ye H, Dai L . Evaluation of the Epidemiologic Efficacy of Eradicating Helicobacter pylori on Development of Gastric Cancer. Epidemiol Rev. 2019; 41(1):97-108. DOI: 10.1093/epirev/mxz006. View

Furihata C, Ohta H, Katsuyama T . Cause and effect between concentration-dependent tissue damage and temporary cell proliferation in rat stomach mucosa by NaCl, a stomach tumor promoter. Carcinogenesis. 1996; 17(3):401-6. DOI: 10.1093/carcin/17.3.401. View

McCabe 4th M, Dilly C . New Causes for the Old Problem of Bile Reflux Gastritis. Clin Gastroenterol Hepatol. 2018; 16(9):1389-1392. DOI: 10.1016/j.cgh.2018.02.034. View

Tatsugami M, Ito M, Tanaka S, Yoshihara M, Matsui H, Haruma K . Bile acid promotes intestinal metaplasia and gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev. 2012; 21(11):2101-7. DOI: 10.1158/1055-9965.EPI-12-0730. View

Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M . A model for gastric cancer epidemiology. Lancet. 1975; 2(7924):58-60. DOI: 10.1016/s0140-6736(75)90498-5. View

10.

Wang F, Meng W, Wang B, Qiao L . Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 2013; 345(2):196-202. DOI: 10.1016/j.canlet.2013.08.016. View

11.

Caston R, Loh J, Voss B, McDonald W, Scholz M, McClain M . Effect of environmental salt concentration on the Helicobacter pylori exoproteome. J Proteomics. 2019; 202:103374. PMC: 6544391. DOI: 10.1016/j.jprot.2019.05.002. View

12.

Malfertheiner P, Peitz U . The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia. Gut. 2005; 54 Suppl 1:i13-20. PMC: 1867793. DOI: 10.1136/gut.2004.041533. View

13.

Dixon M, Genta R, Yardley J, Correa P . Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996; 20(10):1161-81. DOI: 10.1097/00000478-199610000-00001. View

14.

Das K, Kong Y, Bajpai M, Kulkarni D, Geng X, Mishra P . Transformation of benign Barrett's epithelium by repeated acid and bile exposure over 65 weeks: a novel in vitro model. Int J Cancer. 2010; 128(2):274-82. PMC: 3876418. DOI: 10.1002/ijc.25343. View

15.

Gonzalez C, Pardo M, Liso J, Alonso P, Bonet C, Garcia R . Gastric cancer occurrence in preneoplastic lesions: a long-term follow-up in a high-risk area in Spain. Int J Cancer. 2010; 127(11):2654-60. DOI: 10.1002/ijc.25273. View

16.

Choi A, Strate L, Fix M, Schmidt R, Ende A, Yeh M . Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population. Gastrointest Endosc. 2017; 87(4):1023-1028. DOI: 10.1016/j.gie.2017.11.010. View

17.

Park Y, Kim N . Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015; 20(1):25-40. PMC: 4384712. DOI: 10.15430/JCP.2015.20.1.25. View

18.

Li T, Guo H, Li H, Jiang Y, Zhuang K, Lei C . MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia. Gut. 2019; 68(10):1751-1763. PMC: 6839796. DOI: 10.1136/gutjnl-2017-315318. View

19.

Souza R . The role of acid and bile reflux in oesophagitis and Barrett's metaplasia. Biochem Soc Trans. 2010; 38(2):348-52. PMC: 3072824. DOI: 10.1042/BST0380348. View

20.

Song H, Ekheden I, Zheng Z, Ericsson J, Nyren O, Ye W . Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population. BMJ. 2015; 351:h3867. PMC: 4516137. DOI: 10.1136/bmj.h3867. View