The overall goal of Core B, Barrett's cohort management and safety core, is to support the individual projects and the overall specific aims proposed in this Program Project renewal. This goal will be accomplished by providing long-term follow-up of an established cohort of patients who have Barrett's esophagus in which longitudinal investigations of the development of esophageal cancer are conducted. The Seattle Barrett's Esophagus Research Program has an established cohort of 506 study patients with a history of Barrett's esophagus and various stages of progression to cancer. Active study patients are in periodic endoscopic biopsy surveillance for the early detection of esophageal adenocarcinoma. The life-time risk of developing cancer in Barrett's esophagus is low, estimated to be in the range of 5-10%. However, the Seattle Barrett's Esophagus Research Program specializes in the surveillance of higher-risk patients. More than 30% of the Program cohort has a history of high-grade dysplasia and/or a flow cytometric abnormality with an estimated 5-year cumulative cancer risk of 28%-59% and the Program gets regular referrals of these patients because it is difficult for them to be safely or practically managed in the community. Core B, therefore, consists of a substantial number of both higher-risk and lower-risk patients in endoscopic biopsy surveillance providing a unique resource for longitudinal investigations in the development of cancer. Core B is essential to the Program Project. All data generated by the individual Projects can be linked directly to a specific endoscopy, biologic specimen or patient interview coordinated by Core B.
The specific aims of Core B are: 1) To obtain longitudinal tissue samples from Barrett's epithelium for histologic and flow cytometric diagnoses and coordinate the corresponding patient epidemiologic interview, and acquisition of research biopsies and blood samples from the SAME patient at the same study visit to determine the interactions among patient risk and protective factors, somatic genetic and epigenetic abnormalities and clonal evolution in the Barrett's epithelium that can be related to the temporal course of neoplastic progression as proposed in Projects 1, 2, and 3;2) To provide safe, long-term follow-up of a large cohort of patients for molecular genetic and epigenetic investigations and patient risk and protective factors (Projects 1 and 3), the outcomes of which may result in improved patient risk stratification, novel endpoints for epidemiologic investigations (Project 2) and provide scientific rationale for chemopreventive therapies;3) To continue to recruit new patients to the Program by referral from academic- and community-based physicians, thus, maintaining a large well- characterized cohort of patients for the investigations proposed in Projects 1, 2 and 3.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA091955-10
Application #
8293347
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$777,521
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Barry, Peter; Vatsiou, Alexandra; Spiteri, Inmaculada et al. (2018) The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer. Clin Cancer Res 24:4763-4770
Dong, Jing; Levine, David M; Buas, Matthew F et al. (2018) Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus. Clin Gastroenterol Hepatol 16:1598-1606.e4
Xia, Li Charlie; Ai, Dongmei; Lee, Hojoon et al. (2018) SVEngine: an efficient and versatile simulator of genome structural variations with features of cancer clonal evolution. Gigascience 7:
Galipeau, Patricia C; Oman, Kenji M; Paulson, Thomas G et al. (2018) NSAID use and somatic exomic mutations in Barrett's esophagus. Genome Med 10:17
Martinez, Pierre; Mallo, Diego; Paulson, Thomas G et al. (2018) Evolution of Barrett's esophagus through space and time at single-crypt and whole-biopsy levels. Nat Commun 9:794
Dong, Jing; Buas, Matthew F; Gharahkhani, Puya et al. (2018) Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants. Gastroenterology 154:1273-1281.e3
Chowell, Diego; Napier, James; Gupta, Rohan et al. (2018) Modeling the Subclonal Evolution of Cancer Cell Populations. Cancer Res 78:830-839
Fortunato, Angelo; Boddy, Amy; Mallo, Diego et al. (2017) Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks. Cold Spring Harb Perspect Med 7:
Buas, Matthew F; Gu, Haiwei; Djukovic, Danijel et al. (2017) Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma. Metabolomics 13:
Tollis, Marc; Boddy, Amy M; Maley, Carlo C (2017) Peto's Paradox: how has evolution solved the problem of cancer prevention? BMC Biol 15:60

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