Abstract
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.
Highlights
Gastric adenocarcinoma is the fifth most common cancer worldwide.[1]
In this prospective population-based study, hypergastrinemia was associated with an increased risk of gastric adenocarcinoma
Others have previously found that hypergastrinemia is associated with an increased risk of noncardia gastric adenocarcinoma in a study among smokers,[31] and we have previously reported that gastric adenocarcinoma patients with hypergastrinemia at the time of diagnosis more often had carcinomas located in the corpus or fundus (81.8% in hypergastrinemic patients vs 36.2% in normogastrinemic patients, P = .002).[25]
Summary
Gastric adenocarcinoma is the fifth most common cancer worldwide.[1]. The main risk factor for non-cardia gastric adenocarcinoma is atrophic gastritis due to infection with Helicobacter pylori.[2,3,4] In Western populations, the incidence of gastric adenocarcinoma has declined during the last decades, which is probably mainly due to the decreasing prevalence of H pylori infections and subsequently declined incidence of gastric adenocarcinoma of the intestinal histological type (Laurén's classification).[5]. Gastritis causing atrophy of the oxyntic mucosa leads to reduction in acid secretion, and the resulting loss of negative feedback on gastrin release leads to hypergastrinemia
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