Associations Between Leptin, Ghrelin, and Barrett’s Esophagus: A Case-Control Study With Stratified Analyses Presidential Poster

Abstract

Introduction: Obesity, particularly abdominal obesity, is a risk factor for Barrett’s esophagus (BE) independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenesic pathway of esophageal adenocarcinoma. This study aims to evaluate whether ghrelin and leptin may explain the associations between obesity and BE. Methods: We conducted a case control study of cases with Barrett’s esophagus compared with 2 control groups: the first is patients with gastroesophageal reflux disease (GERD) and the absence of Barrett’s esophagus on endoscopy, and the other is a sample from the general population. These controls were frequency matched for age, sex, and geographic region. Unconditional logistic regressions were performed using quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for BE, including waist circumference. We identified potential interactions using a cross-product term analysis and then stratified the analysis by those variables. Results: Elevated levels of ghrelin were associated with BE when compared to the population controls (adjusted odds ratio [OR] 1.87*; 95% confidence interval [CI] 1.11-3.14). However, no relationship between ghrelin and BE was seen when compared to the GERD controls. When we stratified the analysis, ghrelin was associated with BE relative to the population controls among those with a history of smoking (OR 2.32*; CI 1.19-4.54), but not the GERD controls. We did find an association between ghrelin and BE, relative to the GERD controls, among patients with negative Helicobacter pylori (HP) serology (OR 8.45*; CI 1.24-57.58), patients who are currently smoking (OR 8.02*; CI 1.18-54.45), and among females (OR 3.05*; CI 1.16-7.99). No relationship was found between leptin and BE when compared with the population controls, except among patients with a negative HP serology (OR 8.82*; CI 1.10-70.62). However, when compared with the GERD controls, leptin had an overall trend towards an inverse relationship with BE (OR 0.79; CI 0.62-0.99). We also saw an inverse relationship among patients who are not currently smoking (OR 0.46*; CI 0.21-0.98) and among female patients (OR 0.15*, CI-0.04-0.66), compared to the GERD controls. *4th versus 1st quartile Conclusion: Ghrelin was positively associated with the risk of BE, particularly among smokers. This is consistent with previous studies, but it appears that this relationship may be influenced, in part, by GERD, HP and sex. In contrast, leptin was inversely associated with BE among those with GERD symptoms, especially among female patients and non-smokers. Further studies are needed to investigate these relationships and the possible pathophysiology underlying them.