Association between markers of obesity and progression from Barrett's esophagus to esophageal adenocarcinoma

Clin Gastroenterol Hepatol. 2013 Aug;11(8):934-43. doi: 10.1016/j.cgh.2013.02.017. Epub 2013 Mar 1.


Background & aims: Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes.

Methods: We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors.

Results: Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA.

Conclusions: Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE.

Keywords: AHA; American Heart Association; BE; BMI; Barrett's esophagus; Body Mass; CI; Cancer Risk Factor; EA; Esophageal Cancer; HDL; HGD; HMW; HOMA; HR; IDF; International Diabetes Federation; NSAID; Overweight; PPI; SBES; Seattle Barrett's Esophagus Study; T2D; body mass index; confidence interval; esophageal adenocarcinoma; hazard ratio; high molecular weight; high-density lipoprotein; high-grade dysplasia; homeostatic model assessment; nonsteroidal anti-inflammatory drug; proton pump inhibitor; type 2 diabetes mellitus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / epidemiology*
  • Adiponectin / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Barrett Esophagus / complications*
  • Biomarkers / blood*
  • Blood Glucose
  • Esophageal Neoplasms / epidemiology*
  • Female
  • Humans
  • Insulin / blood
  • Leptin / blood
  • Male
  • Metabolic Syndrome / complications
  • Middle Aged
  • Obesity / complications*
  • Risk Assessment


  • Adiponectin
  • Biomarkers
  • Blood Glucose
  • Insulin
  • Leptin