Low Plasma Adiponectin Is Associated with Barrettʼs Esophagus, Controlling for Reflux Symptoms

Abstract

Purpose: Gastroesophageal reflux (GER), male gender, and abdominal obesity are associated with Barrett's esophagus (BE), the accepted precursor of esophageal adenocarcinoma. The assumption has been that the risk abdominal obesity is mediated by a mechanical predilection for GER. We postulated that abdominal obesity is a marker for a more basic mechanism mediated by a secreted factor. Adiponectin is a peptide secreted by adipocytes, and blood levels are inversely associated with abdominal obesity. Adiponectin inhibits inflammation, and low levels have been found to be associated with cancers of the colon, uterus, and breast. We aimed to observe whether blood levels of adiponectin are associated with the risk for BE, controlling for GER. Methods: We performed a case-control study of plasma levels of adiponectin in cases of BE compared with control subjects without BE undergoing elective upper endoscopy for clinical indications. Controls were matched to cases on age, veteran/civilian status, and month of enrollment. Results: Conditional logistic regression from 40 matched pairs showed that cases were more likely than controls to have GER for at least 5 years (OR = 3.8; 95% CI = 1.2, 11.3) and to be male (OR = 29.0; 95% CI = 0.5, 1670). Cases had larger abdominal circumference (for each increment of 10 cm, OR = 1.6; 95% CI = 1.1, 2.3) and higher waist to hip ratios (for each increment of 0.1, OR = 3.2; 95% CI = 1.5, 6.7). For each 10ng/mL decrement in adiponectin the odds of BE increased five-fold (OR = 5.0; 95% CI = 1.2, 20.0). The effect of adiponectin deficiency was similar when controlling for GER duration (OR = 4.4; 95% CI = 1.04, 18.5), and was partially confounded by waist to hip ratio (OR = 1.6; 95% CI = 0.5, 5.3). Unconditional logistic regression from 31 male cases and 20 male controls, controlling for the matching variables, showed that each 10ng/mL decrement in adiponectin trended toward increasing the odds of BE (OR = 2.3; 95% CI = 0.7, 6.9). Conclusions: Low adiponectin blood levels are associated with BE, controlling for GER symptoms. Rather than simply a mechanical effect of obesity promoting GER, the risk of abdominal obesity might be mediated by adiponectin deficiency. Adiponectin deficiency might also mediate the effect of gender on the risk of BE.