Abstract 4857: Short overall telomere length and chromosome 17p-specific telomere length in peripheral blood leukocytes are associated with increased risk of esophageal adenocarcinoma.

Abstract

Abstract Esophageal adenocarcinoma (EAC) is a deadly cancer. The incidence of EAC has increased dramatically in the United States in the past three decades. The biological mechanisms of EAC development are not fully understood. Telomeres are specialized chromatin structures essential for the maintenance of chromosomal integrity. Telomere shortening in somatic tissues has been shown as an early event during carcinogenesis. Previous studies also suggested that constitutive short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers, including esophageal cancer. In this study, we measured overall telomere length in PBLs using real-time PCR in a large case control study of 805 EAC cases and 805 age and gender-matched controls. Furthermore, we developed a fluorescence in site hybridization (FISH) based method to evaluate several chromosome-specific telomere length with the risk of EAC in a subset of subjects. The mean overall telomere length in cases was significantly shorter than that in controls (p<0.001). Dichotomized at the median telomere length in controls, individuals with short PBL telomere length was associated with a 1.53-fold (95% CI, 1.26-1.87) increased risk of EAC. There was a significant dose-effect in quartile analysis: Individuals in quartile with the shortest telomeres showed a nearly 2-fold (95%CI: 1.47-2.57) elevated EAC risk compared to the reference group of the longest quartile of telomere length. In chromosome-specific telomere length analysis, we found that short chromosome 17p-specific telomere length (defined as the ratio of chromosome 17p-specific telomere length to overall telomere length), but not 2p- and 7q-specific telomere length, was associated with a significantly increased risk of EAC (OR=2.02, 95% CI, 1.00-4.08). This study validates that short overall telomere length in PBLs predisposes to EAC with a much larger sample size and supports the role of chromosome 17p aberrations in EAC development. Citation Format: Meng Chen, Jian Gu, Yilei Gong, Jaffer A. Ajani, Xifeng Wu. Short overall telomere length and chromosome 17p-specific telomere length in peripheral blood leukocytes are associated with increased risk of esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4857. doi:10.1158/1538-7445.AM2013-4857