This project covers a broad range of studies which focus on elucidating risk factors for and natural history of esophageal adenocarcinoma and the precursor lesion Barretts esophagus. Barretts esophagus is a metaplastic change in the lower esophagus which is characterized by the replacement of the native squamous cell epithelium with a glandular-type of epithelium. This metaplastic change is thought to be primarily the result of genotoxic damage induced by gastroesophageal refluxacid and bile salts reflux up into the esophagus, exposing cells not equipped to deal with these reactive chemicals. Re-epithelization with the metaplastic Barretts epithelium provides for a tissue which is better able to withstand the exposure to such compounds. However, it also increases the risk of esophageal adenocarcinoma approximately 10-50 fold that of the general population. The incidence of esophageal adenocarcinoma has increased over 650% in the United States over the last 35 years and most individuals present with late stage malignancies, resulting in a 5-year survival rate of less than 20%. This indicates that researchers need to be able to better identify those at high risk and Barretts esophagus is a good starting point. However, although this metaplasia greatly increases the risk of esophageal adenocarcinoma relative to the general population, the absolute risk remains low at around 0.5% or 1 in 200 patient years of follow-up. This is because approximately 90% of individuals who develop esophageal adenocarcinoma are diagnosed at their first (index) endoscopy. Thus, not only do we need to be able to better identify those with high risk (Barretts esophagus) in the general population, we also need to be able to triage these individuals into high and low risk groups so that surveillance resources can be focused on those who most need them, which would make the cost-benefit equation of surveillance endoscopy more attractive. Therefore, the ultimate goals of all the studies within this project seek to better understand the natural history of this disease, risk factors for progression, diagnostic markers and modalities with high sensitivity, and prognostic biomarkers for efficient triaging of risk. The Barrett's Breath Test Pilot (CAS ID:10592) is assessing the utility of quantifying volatile organic compounds (VOCs) in the breath for a future epidemiologic study. Specially, it is assessing what the intraclass correlation coefficients are for VOCs over a 98 day period, with three time points with biological duplicates taken from each of five volunteers. The Barrett's Esophagus Consortium project (CAS ID:10593) is a pooling project that brings together and harmonizes data from five case-control studies of Barrett's esophagus. We have already assessed the exposures tobacco smoking (published in Gastroenterology) and we are now drafting an analysis of BMI and waist circumference in relation to this precursor metaplasia for publication. The Esophageal Cancer in SEER-Medicare project (CAS ID:10633) is assessing metabolic syndrome in relation to Barrett's esophagus, as well as the comparative utility of staging modalities in relation to survival following diagnosis of esophageal adenocarcinoma. The Hormones in Barrett's Esophagus project (CAS ID:10638) is assessing androgens and estrogens in serum from Barrett's esophagus patients and gastroeosphageal reflux disease controls in the BEEDS study based at the National Naval Medical Center. All of these projects are closely aligned to the aims of elucidating the etiology of Barrett's esophagus and esophageal adenocarcinoma as well as providing potential utility for diagnostics and prognostics.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010220-02
Application #
8565475
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
Total Cost
$380,012
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Drahos, Jennifer; Xiao, Qian; Risch, Harvey A et al. (2016) Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium. Int J Cancer 138:55-64
Petrick, Jessica L; Nguyen, Tuyet; Cook, Michael B (2016) Temporal trends of esophageal disorders by age in the Cerner Health Facts database. Ann Epidemiol 26:151-4.e1-4
Drahos, Jennifer; Li, Lin; Jick, Susan S et al. (2016) Metabolic syndrome in relation to Barrett's esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink. Cancer Epidemiol 42:9-14
Ek, Weronica E; Lagergren, Katarina; Cook, Michael et al. (2016) Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma. Int J Cancer 138:1146-52
Cook, Michael B; Wood, Shannon N; Cash, Brooks D et al. (2015) Association between circulating levels of sex steroid hormones and Barrett's esophagus in men: a case-control analysis. Clin Gastroenterol Hepatol 13:673-82
Wani, Sachin; Das, Ananya; Rastogi, Amit et al. (2015) Endoscopic ultrasonography in esophageal cancer leads to improved survival rates: results from a population-based study. Cancer 121:194-201
Drahos, Jennifer; Ricker, Winnie; Parsons, Ruth et al. (2015) Metabolic syndrome increases risk of Barrett esophagus in the absence of gastroesophageal reflux: an analysis of SEER-Medicare Data. J Clin Gastroenterol 49:282-8
Thrift, Aaron P; Cook, Michael B; Vaughan, Thomas L et al. (2014) Alcohol and the risk of Barrett's esophagus: a pooled analysis from the International BEACON Consortium. Am J Gastroenterol 109:1586-94
Kubo, Ai; Cook, Michael Blaise; Shaheen, Nicholas J et al. (2013) Sex-specific associations between body mass index, waist circumference and the risk of Barrett's oesophagus: a pooled analysis from the international BEACON consortium. Gut 62:1684-91
Vahabzadeh, Babac; Seetharam, Anil B; Cook, Michael B et al. (2012) Validation of the Prague C & M criteria for the endoscopic grading of Barrett's esophagus by gastroenterology trainees: a multicenter study. Gastrointest Endosc 75:236-41

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