Abstract
BackgroundA few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting.MethodsIn total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared.ResultsSerum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70–44.59) for cardia and 6.58 (1.26–34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36–23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10–0.64)].ConclusionInverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.
Highlights
Gastric and esophageal cancers are among the most prevalent malignancies worldwide, claiming more than 1,000,000 lives annually [1]
Long-term mucosal damage associated with Helicobacter pylori (H.pylori) infection results in a cascade of atrophic gastritis, intestinal metaplasia, and dysplasia leading to cancer [2]
We aimed to investigate relationship between serum ghrelin and four common upper gastrointestinal cancers, namely gastric adenocarcinoma, esophageal adenocarcinoma and esophageal squamous cell carcinoma (SCC), all in a population from the Ardabil Province, Iran known to have a high incidence of gastric cancer [16]
Summary
Gastric and esophageal cancers are among the most prevalent malignancies worldwide, claiming more than 1,000,000 lives annually [1]. In the process of gastric carcinogenesis, hypochlorhydria, is caused by loss of parietal cells in atrophic gastritis and severe chronic inflammation of the gastric body mucosa [3,4]. Concurrent loss of chief cells from deeper gastric glands may lead to a reduction locally and in the serum of pepsinogen I (PGI) and pepsinogen II (PGII). As well as hydrochloric acid and pepsinogen, the gastric mucosa secretes several other biologically active peptides and hormones. Ghrelin is a 28-amino acid peptide hormone [6], produced predominantly by the P/D1 cells of gastric oxyntic gland and is mainly found in the proximal stomach [7]. A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting
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