Hypergastrinemia is associated with an increased risk of gastric adenocarcinoma with proximal location: A prospective population‐based nested case‐control study

• Published in: International journal of cancer Vol. 148; no. 8; pp. 1879 - 1886
• Main Authors: Ness‐Jensen, Eivind, Bringeland, Erling Audun, Mattsson, Fredrik, Mjønes, Patricia, Lagergren, Jesper, Grønbech, Jon Erik, Waldum, Helge Lyder, Fossmark, Reidar
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.04.2021; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma; Animal models; Body mass index; Cancer; Cancer Epidemiology; Carcinogenesis; epidemiology; Gastric cancer; Gastrin; Intestine; Lauren; Medical research; Population-based studies; stomach; Tobacco smoking; epidemiology; cancer; stomach; Lauren; gastrin
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.33354

The incidence of proximal gastric adenocarcinoma is increasing among younger adults. Rodent models have shown that hypergastrinemia causes carcinogenesis in the proximal stomach. The aim of our study was therefore to assess if hypergastrinemia was associated with an increased risk of developing gastric adenocarcinoma also in humans. A prospective population‐based nested case‐control study within the Nord‐Trøndelag Health Study (HUNT) cohort, Norway, was used to assess this association. Serum was collected from 78 962 participants in 1995 to 1997 and 2006 to 2008. In the cohort, 181 incident gastric adenocarcinoma cases were identified from the Norwegian Cancer and Patient Registries through 2015 and matched with 359 controls. The risk of gastric adenocarcinoma was compared between participants with prediagnostic hypergastrinemia (>60 pmol/L) and normal serum gastrin (≤60 pmol/L). Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for body mass index, tobacco smoking and comorbidity. Hypergastrinemia was associated with increased risk of gastric adenocarcinoma overall (OR 2.2, 95% CI 1.4‐3.4) and in particular for gastric adenocarcinoma with proximal location (OR 6.1, 95% CI 2.7‐13.8), but not with gastric adenocarcinoma with distal location (OR 1.7, 95% CI 0.9‐3.4). Moreover, hypergastrinemia was associated with an increased risk of gastric adenocarcinoma of intestinal histological type (OR 3.8, 95% CI 1.8‐7.9), but not for diffuse histological type (OR 1.6, 95% CI 0.7‐3.7). In conclusion, hypergastrinemia was associated with an increased risk of proximal and intestinal type gastric adenocarcinoma. What's new? The incidence of proximal gastric adenocarcinoma has been reported to increase among younger adults in Western countries. Rodent models have shown that serum gastrin levels above the normal range cause carcinogenesis in the proximal stomach. In this first prospective population‐based study on the association between hypergastrinemia and gastric adenocarcinoma, the risk of gastric adenocarcinoma in the proximal stomach, but not in the distal stomach, was markedly increased in hypergastrinemic individuals. The finding supports the hypothesis that hypergastrinemia mediates the development of gastric adenocarcinoma in the proximal stomach, where mucosal proliferation is stimulated by gastrin.