Sa1879 Obesity, Adipokines, Inflammatory Markers and Risk of Neoplastic Progression in BE: A Cohort Study

Abstract

Background Barrett's Esophagus (BE) is the precancerous lesion for esophageal adenocarcinoma (EAC). Several studies have indicated that obesity, especially abdominal, is a risk factor for BE. In addition, recent studies have shed light on the role of adipokines (leptin, adiponectin) and inflammatory biomarkers in the development of BE. However, the role of obesity and its biomarkers in the neoplastic progression of BE is unclear. The goal of our cohort study was to evaluate the association between baseline obesity (measured by WHR and BMI) and proand anti-inflammatory biomarkers (circulating adiponectin, leptin, IL1b, IL-6, IL-8, IL-10, and IL-12) and risk of progression to dysplasia or EAC. Methods We evaluated prospectively recruited BE cases during 2008-2013. All patients completed a questionnaire on GERD symptoms and medication use, and had anthropometric measurements (height, weight, waist and hip circumference) and a research blood sample was collected at baseline. BE was defined by endoscopic appearance combined with pathologic findings of intestinal metaplasia. We included patients who had at least one follow up endoscopy through November 19th 2014. BE neoplastic progression was defined as change from non-dysplastic BE to low grade dysplasia (LGD), high grade dysplasia (HGD), or EAC; or change from LGD to HGD or EAC; or change of HGD to EAC. The main exposures were baseline BMI, WHR and circulating levels of biomarkers. Major confounding factors were medications (PPI, statin, H2RA, aspirin, NSAID), GERD (symptoms, severity, frequency) and demographics (race, age, sex). The risk of neoplastic progression was examined in multivariate Cox proportional hazards analysis. Results A total of 178 patients with BE met the inclusion and exclusion criteria; 98% men, 92% white and average age 61.8 years. At baseline, 94% of patients had non-dysplastic BE. In a follow up of 804 patient years, 34 patients (19.10%) progressed to dysplastic BE, and the other 144 patients (80.9%) remained nondysplastic. The likelihood of BE neoplastic progression showed a non-significant increase with obesity (BMI>30) (adjusted HR=3.07, 95%CI 0.74-12.7) and high WHR (adjusted HR: 1.66, 0.22-12.7), and a significant decrease with elevated log IL-1 β I (HR=0.33, 95%C0.120.88) adjusted for age, race, sex, NSAID and statin. There were no associations with circulating serum levels of adiponectin, leptin, IL-6, IL-8, IL-10 or IL-12 levels. Conclusions The data are suggestive of a role for obesity and low levels of anti-inflammatory cytokine (IL-1 β) in the neoplastic progression of BE. These preliminary findings need to be confirmed in a larger dataset and longer follow up. Associations between baseline obesity and inflammation and risk of progression