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Large\u2010scale regional studies revealed an alternative approach, by suggesting a positive relationship between <jats:italic>Hp\u2010<\/jats:italic>I and EAC development. Regarding pathophysiology, <jats:italic>Hp\u2010<\/jats:italic>I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD\u2212Barrett's esophagus (BE)\u2212EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. <jats:italic>Hp<\/jats:italic> contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase\u20102, and prostaglandins; Ki\u201067 is also expressed and represents an index of BE\u2010related malignancy. Moreover, <jats:italic>Hp\u2010<\/jats:italic>I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between <jats:italic>Hp\u2010<\/jats:italic>I and EAC. Although further studies are necessary to establish a pathophysiologic risk between <jats:italic>Hp\u2010<\/jats:italic>I and the GERD\u2212BE\u2212EAC sequence, the theory of <jats:italic>Hp<\/jats:italic> protection against GERD seems outdated.<\/jats:p>","DOI":"10.1111\/nyas.14168","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T13:12:01Z","timestamp":1563282721000},"page":"12-17","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A perspective on risk factors for esophageal adenocarcinoma: emphasis on <i>Helicobacter pylori<\/i> infection"],"prefix":"10.1111","volume":"1452","author":[{"given":"Jannis","family":"Kountouras","sequence":"first","affiliation":[{"name":"Department of Medicine, Second Medical Clinic Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki  Macedonia 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