title: Ghrelin and Leptin Have a Complex Relationship with Risk of Barrett's Esophagus.
abstract: BACKGROUND
  Abdominal obesity is a risk factor for Barrett's esophagus independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenic pathway of esophageal adenocarcinoma.
  
  
  OBJECTIVE
  To evaluate whether ghrelin and leptin may partially explain the association between obesity and Barrett's esophagus.
  
  
  METHODS
  We conducted a case-control study using patients with a new diagnosis of Barrett's esophagus (cases) and two control groups frequency matched to cases for age, gender, and geographic region: (1) patients with gastroesophageal reflux disease (GERD) and (2) a sample of the general population. We generated odds ratios using logistic regressions to evaluate quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for Barrett's esophagus. We evaluated potential interaction variables using cross products and ran stratified analyses to generate stratum-specific odds ratios.
  
  
  RESULTS
  A total of 886 participants were included in the analysis. Higher ghrelin concentrations were associated with an increased risk of Barrett's esophagus, when compared to the population controls, but not the GERD controls. Ghrelin concentrations were not associated with the frequency of GERD symptoms, but ghrelin's relationship with Barrett's esophagus varied significantly with the frequency of GERD symptoms. Leptin concentrations were positively associated with at least weekly GERD symptoms among the population controls and were inversely associated with Barrett's esophagus only among the GERD controls. Adjusting for waist circumference did not change the main associations.
  
  
  CONCLUSIONS
  Higher levels of ghrelin were associated with an increased risk of Barrett's esophagus among the general population. In contrast, leptin was positively associated with frequent GERD symptoms, but inversely associated with the risk of Barrett's esophagus among the GERD controls.
authors.affiliation: University of Kansas Medical Center, 3901 Rainbow Blvd, Mail stop 1023, Kansas City, KS, 66160, USA. sthomas10@kumc.edu.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Thomas
authors.affiliation: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA, 94612, USA. lucy.m.almers@kp.org.
authors.forename: Lucy
authors.initials: L
authors.lastname: Almers
authors.affiliation: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA, 94612, USA. jennifer.l1.schneider@kp.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. jlgraham@ucdavis.edu.|Department of Nutrition, University of California, Davis, Davis, CA, USA. jlgraham@ucdavis.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Graham
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. pjhavel@ucdavis.edu.|Department of Nutrition, University of California, Davis, Davis, CA, USA. pjhavel@ucdavis.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
authors.affiliation: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA, 94612, USA. douglas.corley@kp.org.|Kaiser Permanente Medical Center, 2425 Geary Blvd, M160, San Francisco, CA, 94121, USA. douglas.corley@kp.org.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Corley
mesh_terms: D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D020738:Leptin / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; C515349:GHRL protein, human; D054439:Ghrelin; D020738:Leptin
keywords: Barrett’s esophagus; GERD; Ghrelin; Leptin; Obesity