title: Does long-term profound inhibition of gastric acid secretion increase the risk of ECL cell-derived tumors in man?
abstract: OBJECTIVE
  Since the description of ECL cell-derived tumors in rodents after long-term profound acid inhibition inducing hypergastrinemia, there has been concern that proton pump inhibitors (PPIs) could also do that in man. The recent description of a Spanish family with gastric ECL cell tumors at the age of about 30 years secondary to a defect in the proton pump due to mutation in the ATP4A gene clearly shows that hypergastrinemia alone also is sufficient to induce ECL cell neoplasia in man. The present review aims to evaluate the risk of gastric neoplasia secondary to gastric acid inhibition.
  
  
  METHODS
  Literature (MEDLINE) was searched for the role of the ECL cell in gastric carcinogenesis in animals and man in general and particularly secondary to long-term inhibition of acid secretion.
  
  
  RESULTS
  An important proportion of patients treated with PPI develops hypergastrinemia causing ECL cell hyperplasia and the first descriptions of ECL cell carcinoids secondary to PPI have been reported. The role of the ECL cell has hitherto been under estimated in gastric carcinogenesis in man where for instance the signet ring cell type of gastric carcinoma seems to originate from the ECL cell.
  
  
  CONCLUSIONS
  The first two of three steps in rodent ECL cell carcinogenesis (hyperplasia, carcinoid, and carcinoma) secondary to PPI dosing, have been described for man. It is every reason to believe that the final step, gastric carcinoma, will develop also in man. Clinical decisions should be based not only on so-called evidence based medicine, but also on physiological knowledge and animal studies.
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;|b Department of Gastroenterology and Hepatology , St. Olavs Hospital , Trondheim , Norway.
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;|b Department of Gastroenterology and Hepatology , St. Olavs Hospital , Trondheim , Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Hauso
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;|b Department of Gastroenterology and Hepatology , St. Olavs Hospital , Trondheim , Norway.
authors.forename: Eiliv
authors.initials: E
authors.lastname: Brenna
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;|b Department of Gastroenterology and Hepatology , St. Olavs Hospital , Trondheim , Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Qvigstad
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;|b Department of Gastroenterology and Hepatology , St. Olavs Hospital , Trondheim , Norway.
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
mesh_terms: D000818:Animals; D019861:Enterochromaffin-like Cells / Q000473:pathology / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012377:Rodentia; D013274:Stomach Neoplasms / Q000139:chemically induced*
chemical_list: D054328:Proton Pump Inhibitors
keywords: ECL cell; gastric acid inhibition; gastric cancer; gastric carcinoid; gastrin