Abstract 27: Telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma.

Abstract

Abstract Background: Repeated injury of the esophagus by chronic gastroesophageal reflux (GER) is associated with the development of Barrett's esophagus (BE), a condition in which the squamous epithelium is replaced by a metaplastic columnar epithelium. A proportion of individuals diagnosed with BE progress to esophageal adenocarcinoma (EAC), which has considerably increased in incidence in many Western countries over the past four decades. Major risk factors associated with BE and EAC, such as obesity, smoking and gastroesophageal reflux (GER), are all contributors to the presence of chronic inflammation and oxidative damage. Unlike other areas of the chromosome that have effective repair systems to deal with oxidative damage, telomeres are not as well maintained and telomere length may reflect the impact of chronic inflammation. We investigated whether leukocyte telomere length was associated with BE or EAC risk compared to population-based controls in a pooled analysis of seven studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Methods: Telomere length was measured by quantitative-PCR using leukocyte DNA samples. Participants included 1,198 cases (395 with EAC, 403 with BE, 400 with GER) and 749 population-based controls. The association of telomere length (in tertiles) along the continuum of disease progression from GER to BE to EAC was calculated using study-specific odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models, adjusted for age, sex, smoking status, alcohol consumption, BMI and education. Summary risk estimates were obtained using a random effects meta-analysis models. Results: Shorter telomeres were associated with decreased risks of EAC (OR 0.84; 95% CI 0.47-1.48) and BE (OR 0.68; 95% CI 0.46-1.01), when compared to population-based controls, though not statistically significant. In addition, subjects with shorter telomeres were associated with a decreased risk of GER (OR 0.43; 95% CI 0.18-1.01), compared to population-based controls. Conclusion: Telomere length may play a role in the progression from chronic reflux to BE and EAC. Citation Format: E. Christina Persson, Linda M. Liao, Rosana Risques, Donna Prunkard, Carol Giffen, Wong-Ho Chow, Thomas L. Vaughan, on behalf of the Barrett's Esophagus, Adenocarcinoma Consortium (BEACON) Investigators. Telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 27.