Inflammation and oxidative stress markers and esophageal adenocarcinoma incidence in a Barrett's esophagus cohort

Abstract

Background: Persons with Barrett's esophagus experience increased risk of esophageal adenocarcinoma. Prediagnostic inflammation markers predict several cancers, but their role in predicting esophageal adenocarcinoma 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, the mean 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 adenocarcinoma. 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. Persons with IL6 levels above the median also had almost 2-fold increased risk [HR and 95% CI adjusted for age and gender, and further adjusted for waist-hip ratio and smoking were 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.

Conflict of interest statement

Conflict of interest: The authors declare that they have no conflict of interest.

©2014 American Association for Cancer Research.

Figures

Figure 1

Relationship between association of EA with plasma CRP(A) and IL-6(B) with follow-up restricted to 3 and 5 years from baselinea aAll models adjusted for confounding effects of age, gender, smoking (pack-years) and obesity (waist-hip ratio)