Research Article Inflammation and Oxidative Stress Markers and Esophageal Adenocarcinoma Incidence in a Barrett's Esophagus Cohort

Background: Persons with Barrett’s esophagus experience increased risk of esophageal adenocarcinoma. Prediagnostic inflammation markers predict several cancers, but their role in predicting esophageal adeno-carcinoma is unknown. Methods: We investigated whether biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor (sTNF) receptors I and II], and of oxidative stress (F2-isoprostanes) predicted progression to esophageal adenocarcinoma in a prospective cohort of 397 patients with Barrett’s esophagus, 45 of whom developed esophageal adenocarcinoma. Biomarkers were measured in stored plasma samples from two time points during follow-up, themean of which served as the primary predictor. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression. Results: CRP level above the median was associated with an 80 % increased risk of esophageal adenocar-cinoma. The HR and 95 % CI adjusted for age, gender, and further adjusted for waist–hip ratio and smoking were 1.98 (1.05–3.73) and 1.77 (0.93–3.37), respectively, with Ptrend for continuous CRP 0.04. Personswith IL6 levels above themedian also had almost 2-fold increased risk [HR and 95%CI adjusted for age and gender, and further adjusted forwaist–hip ratio and smokingwere 1.95 (1.03–3.72) and 1.79 (0.93–3.43), respectively, but no evidence of a trend was observed]. Concentrations of TNF receptors and F2-isoprostanes were not associated with esophageal adenocarcinoma risk. Conclusions: Further research is needed to evaluate the role of inflammation and associated markers in esophageal adenocarcinoma development in persons with Barrett’s esophagus. Impact: This prospective study suggests that inflammation markers, particularly CRP and IL6, may help identify persons at higher risk of progression to esophageal adenocarcinoma.Cancer Epidemiol Biomarkers Prev; 23(11); 1–11. 2014 AACR