Gastrin and upper GI cancers

•Gastrin promotes proximal gastric cancer development but inhibits distal cancer development.•PPI use increases serum gastrin levels and may affect gastric carcinogenesis.•A subset of gastric antral and cardia stem cells express CCK2R.•Hypergastrinemia promotes Barrett's esophageal metaplasia arising from cardia stem cells.

Gastrin was initially identified as the hormone primarily responsible for gastric acid secretion, but was subsequently shown to be a growth factor for the proximal stomach, acting through the gastrin receptor CCK2R. Studies in the past several decades have explored the role of gastrin, along with its incompletely processed precursors, in cancer development. The growth in long-term PPI use has frequently led to elevations in serum gastrin levels in patients with upper GI disease, including GERD, peptic ulcers, and chronic gastritis. However, while accumulated evidence has shown that gastrin likely does not promote — and may even suppress — distal antral gastric cancer, questions have now arisen regarding possible effects of gastrin on the development of gastric cardia cancer or esophageal adenocarcinoma at gastroesophageal junction. Here, we provide an overview of the possible roles of these gastrin peptides in upper GI cancer.

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