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 750% in the United States over the last 30 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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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Petrick, Jessica L; Kelly, Scott P; Liao, Linda M et al. (2017) Body weight trajectories and risk of oesophageal and gastric cardia adenocarcinomas: a pooled analysis of NIH-AARP and PLCO Studies. Br J Cancer 116:951-959
Cook, Michael B; Coburn, Sally B; Lam, Jameson R et al. (2017) Cancer incidence and mortality risks in a large US Barrett's oesophagus cohort. Gut :
Drahos, Jennifer; Ricker, Winnie; Pfeiffer, Ruth M et al. (2017) Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: An analysis of SEER-Medicare data. Cancer 123:657-665
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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
Kendall, Bradley J; Rubenstein, Joel H; Cook, Michael B et al. (2016) Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis. Clin Gastroenterol Hepatol 14:1412-1419.e3
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 26:151-154.e4
Cook, Michael B; Drahos, Jennifer; Wood, Shannon et al. (2016) Pathogenesis and progression of oesophageal adenocarcinoma varies by prior diagnosis of Barrett's oesophagus. Br J Cancer 115:1383-1390

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