Serum Ghrelin; A New Surrogate Marker of Gastric Mucosal Alterations in Upper Gastrointestinal Carcinogenesis

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.

Serum ghrelin and esophageal and gastric cancer in two cohorts in China

“…Our prior prospective studies observed that low baseline ghrelin levels were associated with risk of gastric adenocarcinoma, esophagogastric junctional adenocarcinoma, esophageal squamous cell carcinoma and colorectal adenocarcinoma incidence in Western populations . However, the current analysis is the first prospective epidemiologic study of circulating ghrelin conducted in China, a region with a very high burden of esophageal and gastric cancer .…”

“…Circulating ghrelin levels also increase in the presence of low BMI and malnutrition, and ghrelin levels decrease with increasing BMI and obesity . The NIT study, in particular, was undertaken in a population who could be classified as under nourished using any metric which likely explains the higher concentrations of this orexigenic hormone in the NIT cohort (mean ghrelin 1,022 pg/ml controls), relative to Shanghai (mean ghrelin 743 pg/ml controls) or previous studies in Finland (mean ghrelin 802 pg/ml controls) and Iran (median ghrelin 672 pg/ml controls) . Future studies investigating the association of ghrelin levels with subsequent incidence of esophageal, and other cancers, are clearly merited.…”

Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention

“…Chronic inflammation and atrophic gastritis due to H. pylori infection may reduce production of ghrelin, thus low serum ghrelin may indicate higher risk of GC. This theory has so far been supported by a case-control and a cohort study, showing a substantial and statistically significant increased risk of both cardia and noncardia GC associated with lower concentrations of ghrelin (152, 153). In these studies, serum ghrelin was a predictor of GC independent of serum PGI or PGI/II ratio.…”

Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study

“…In this previous study, the baseline serum ghrelin concentrations in controls were almost identical in range to those seen here. Lastly, a cross-sectional case–control study of gastric cancer (non-cardia and cardia), oesophageal adenocarcinoma and oesophageal squamous cell carcinoma within the Aras Gastrointestinal Health Survey (Iran)17 also reported a statistically significant inverse relationship between serum ghrelin and gastric cancer (both non-cardia and cardia) and oesophageal squamous cell carcinoma, although no significant association was found with oesophageal adenocarcinoma. Together, these reports indicate that low-serum ghrelin levels are significantly associated with risk of all four major upper GI cancers: non-cardia gastric adenocarcinoma, gastric cardia/oesophagogastric junctional adenocarcinoma, oesophageal adenocarcinoma and oesophageal squamous cell carcinoma, despite differing aetiological and risk factor profiles across these four sites.…”