The incidence of esophageal adenocarcinomas (EAC) has increased at an alarming rate (>400%) in the last few decades far exceeding any other cancer type in the United States, while the prognosis has remained poor (1). Most EACs are initiated by replacement of normal squamous epithelium with metaplastic mucosa known as Barrett's esophagus (BE), which subsequently progress through a dysplastic stage into invasive carcinomas (2). Although BE-affected individuals carry a 30-125 fold greater risk of developing EAC when compared to an age-matched population (3), the estimated rate of cancer progression among BE individuals is only 1 per 200 patient-years (2). This makes it difficult to identify BE patients who are at an increased risk for cancer development, and is one of the major clinical challenges in this disease. Endoscopy-based surveillance in BE patients has shown only a minimal impact in reducing cancer mortality, and is certainly not cost-effective (2). Though histology based evaluation for high-grade dysplasia (HGD) is currently used for assessing cancer risk in patients with BE, the approach is not optimal owing both to the marked inter-observer variability in interpreting dysplasia (4), and to the highly variable rates of progression to EAC (16-50% over 7 years) among HGD cases (2). Therefore, identification of novel biomarkers that reliably aid in risk stratification in BE would allow for the development of more rational surveillance strategies aimed at early cancer detection, in addition to providing a novel class of therapeutic targets for this deadly disease. Moreover, it will additionally help in curtailing health care costs by refining current screening and surveillance programs. Accordingly, the primary objective of this proposal is to identify RNA-based biomarkers associated with the risk of malignant progression in BE.

National Institute of Health (NIH)
Specialized Center--Cooperative Agreements (U54)
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Case Western Reserve University
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Fecteau, Ryan E; Kong, Jianping; Kresak, Adam et al. (2016) Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia. JAMA Oncol 2:1333-1339
Sun, Xiangqing; Elston, Robert C; Barnholtz-Sloan, Jill S et al. (2016) Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm. Cancer Epidemiol Biomarkers Prev 25:727-35
Sun, Xiangqing; Elston, Robert; Falk, Gary W et al. (2016) Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas. Mol Genet Genomic Med 4:407-19
Curtius, Kit; Wong, Chao-Jen; Hazelton, William D et al. (2016) A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett's Esophagus. PLoS Comput Biol 12:e1004919
Kaz, Andrew M; Wong, Chao-Jen; Varadan, Vinay et al. (2016) Global DNA methylation patterns in Barrett's esophagus, dysplastic Barrett's, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use. Clin Epigenetics 8:111
Blum, Andrew E; Venkitachalam, Srividya; Guo, Yan et al. (2016) RNA Sequencing Identifies Transcriptionally Viable Gene Fusions in Esophageal Adenocarcinomas. Cancer Res 76:5628-5633
Krishnamoorthi, Rajesh; Borah, Bijan; Heien, Herbert et al. (2016) Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort. Gastrointest Endosc 84:40-46.e7
Fiuza-Luces, C; Simpson, R J; Ramírez, M et al. (2016) Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients. Bone Marrow Transplant 51:13-26
Cummings, Linda C; Kou, Tzuyung Doug; Schluchter, Mark D et al. (2016) Outcomes after endoscopic versus surgical therapy for early esophageal cancers in an older population. Gastrointest Endosc 84:232-240.e1
Kong, Jianping; Whelan, Kelly A; Laczkó, Dorottya et al. (2016) Autophagy levels are elevated in barrett's esophagus and promote cell survival from acid and oxidative stress. Mol Carcinog 55:1526-1541

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