Dear Editor,
Holmberg et al. described reduction of gastric and oesophageal adenocarcinomas following discontinuation of proton-pump inhibitor therapy [1]. While PPIs have for long been suspected to cause gastric adenocarcinomas originating from the enterochromaffin-like (ECL) cell via hypergastrinemia [2, 3], a role by PPIs in oesophageal adeno-carcinogenesis has not been accepted. Gastrin, a peptide hormone, affects cell function only via the CCK-2 (gastrin) receptor, which is localized on the ECL cell, and possibly on some cells in Barrett’s mucosa [4]. The CCK-2 receptor in Barrett’s mucosa was postulated to mediate the oesophageal adeno-carcinogenic effect [1]. However, previous studies have indicated that PPI treatment reduces the risk of oesophageal carcinomas, and the gastrin antagonist netazepide failed to affect Barrett’s oesophagus [5]. Furthermore, in just published AGA guidelines on Barrett’s oesophagus PPI treatment was still advocated. Therefore, the role of PPIs in oesophageal adeno-carcinogenesis is not clear, and future studies are required.
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References
Holmberg D, Mattsson F, Xie S, et al. Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy. J Gastroenterol. 2022;57:942–51.
Havu N. Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion. 1986;35(Suppl 1):42–55.
Waldum HL, Haugen OA, Isacsen C, et al. Enterochromaffin-like (ECL) tumour cells in the diffuse but not the intestinal type of gastric carcinomas. Eur J Gastroenterol Hepatol. 1991;3:245–9.
Haigh CR, Attwood SE, Thompson DG, et al. Gastrin induces proliferation in Barrett’s metaplasia through activation of the CCK2 receptor. Gastroenterology. 2003;124:615–25.
Abrams JA, Del Portillo A, Hills C, et al. Randomized controlled trial of the Gastrin/CCK(2) receptor antagonist netazepide in patients with Barrett’s esophagus. Cancer Prev Res (Phila). 2021;14:675–82.
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Waldum, H. Risk of gastric and oesophageal adenocarcinomas following discontinuation of long-term proton-pump inhibitor therapy. J Gastroenterol 58, 182 (2023). https://doi.org/10.1007/s00535-022-01943-y
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DOI: https://doi.org/10.1007/s00535-022-01943-y