{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:30:12Z","timestamp":1783481412281,"version":"3.55.0"},"reference-count":0,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,12,25]],"date-time":"2001-12-25T00:00:00Z","timestamp":1009238400000},"content-version":"vor","delay-in-days":1211,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[1998,9]]},"abstract":"Background.<\/jats:title> Helicobacter pylori<\/jats:italic> infection is accepted to be associated with two mutually exclusive diseases: duodenal ulcer and gastric cancer. Attention has recently focused on possible relationships between H. pylori<\/jats:italic> and gastroesophageal reflux disease and its complications such as adenocarcinoma of the gastric cardia. The aim of this study was to provide a framework for explaining the seemingly paradoxical associations between H. pylori<\/jats:italic> and various gastrointestinal diseases.<\/jats:p><\/jats:sec>Methods.<\/jats:title>Available data regarding H. pylori<\/jats:italic> infection, cagA<\/jats:italic>, acid secretion, corpus gastritis, and gastroesophageal reflux disease (GERD) and its complications are reviewed, and testable hypotheses are presented.<\/jats:p><\/jats:sec>Results.<\/jats:title>Linking the type of H. pylori<\/jats:italic> (cagA<\/jats:italic>\u2010positive vs. cagA<\/jats:italic>\u2010negative), the pattern and intensity of inflammation, and acid secretion explains the apparent paradoxes in the associations between H. pylori<\/jats:italic> and gastric cancer, duodenal ulcer, and GERD. Although H. pylori<\/jats:italic> is inhibited by bile, a duodenal acid load sufficient to lower the average pH to precipitate bile acids overcomes that inhibition. H. pylori<\/jats:italic> that contain a functional cag<\/jats:italic> pathogenicity island produce a vigorous inflammatory response. The severity of mucosal inflammation predicts likelihood of different outcomes (e.g., in the bulb with likelihood of developing duodenal ulcer, and in the corpus with the degree of reduction in acid secretion and the rate of development of multifocal atrophic gastritis). Development of H. pylori<\/jats:italic> corpus gastritis is promoted by profound inhibition of acid secretion (e.g., childhood infections or a high level of antisecretory therapy). The CagA protein, or the cagA<\/jats:italic> gene, is a marker for enhanced inflammation, but CagA is not directly involved in the pathogenesis of gastric cancer or duodenal ulcer disease, nor is it a reliable indicator of the presence of a functional cag<\/jats:italic> pathogenicity island.<\/jats:p><\/jats:sec>Conclusion.<\/jats:title>The relationship between the type of H. pylori<\/jats:italic> infection, presence or absence of a functional cag<\/jats:italic> pathogenicity island, corpus inflammation, and acid secretion explains the duodenal ulcer\/gastric cancer paradox and the relationship between H. pylori<\/jats:italic> infection and the complications of GERD. The predicted rank order for the presence of GERD and its complications (peptic stricture, Barrett\u2019s esophagus, and adenocarcinoma of the gastric cardia) is highest in the population without H. pylori<\/jats:italic> infection, less in those with H. pylori<\/jats:italic> infection, and least in those infected with cagA<\/jats:italic>\u2010positive H. pylori.<\/jats:italic> Controversy and confusing epidemiological observations will continue unless future studies provide data on the gastric corpus histology (or acid secretion) as well as regarding the presence or absence of a functional and intact cag<\/jats:italic> pathogenicity island of the infecting organism.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1523-5378.1998.08031.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T23:20:56Z","timestamp":1047424856000},"page":"145-151","source":"Crossref","is-referenced-by-count":133,"title":["H. pylori<\/i> and cagA<\/i>: Relationships with Gastric Cancer, Duodenal Ulcer, and Reflux Esophagitis and Its Complications"],"prefix":"10.1111","volume":"3","author":[{"given":"David Y.","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,25]]},"container-title":["Helicobacter"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1523-5378.1998.08031.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1523-5378.1998.08031.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1523-5378.1998.08031.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T05:29:41Z","timestamp":1694410181000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1523-5378.1998.08031.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1998,9]]}},"alternative-id":["10.1046\/j.1523-5378.1998.08031.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1523-5378.1998.08031.x","archive":["Portico"],"relation":{},"ISSN":["1083-4389","1523-5378"],"issn-type":[{"value":"1083-4389","type":"print"},{"value":"1523-5378","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9]]}}}