The primary objective of this career development award application is to provide me with the proper mentored environment to progress and develop into a successful independent researcher in risk factors for progression in esophageal neoplasia. The incidence of esophageal cancer, particularly adenocarcinoma, is rising rapidly in western countries, and the large majority of esophageal cancer patients die from complications of metastatic disease. However, factors that affect site-specific metastasis have not been well described. Our preliminary research indicates that, in patients with esophageal cancer, smoking may increase the risk of lung metastasis, while alcohol significantly reduces the risk of liver metastasis.
The specific aims of the research proposal are to: (1) determine whether smoking increases the risk of lung metastasis from esophageal cancer;(2) determine whether alcohol decreases the risk of liver metastasis from esophageal cancer;and (3) determine whether smoking and alcohol impact site-specific metastatic risk via effects on the primary tumor (the """"""""seed""""""""), the site of metastasis (the """"""""soil""""""""), or both. In order to accomplish Aims 1 and 2, I propose to conduct a nested case-control study from a cohort of esophageal cancer patients to confirm the site-specific effects of smoking and alcohol on patterns of metastasis. Cases will be defined as esophageal cancer patients with lung or liver metastases, and controls as those patients without lung or liver metastases. In order to accomplish Aim 3, exploratory analyses will be performed of the primary tumor and of sites of metastasis. Primary tumor tissue will be analyzed for expression of high mobility group proteins Al and A2, potential markers of metastatic behavior. Lung damage will be quantified by forced expiratory volume (one second) and by the major urinary prostaglandin-E2 metabolite, an experimental measure of tobacco-induced lung injury. Liver fibrosis will be estimated using an algorithm comprised of three serum markers (hyaluronic acid, procollagen III, and TIMP-1). The identification of lifestyle risk factors for site-specific metastasis and their site of action (""""""""seed"""""""" or """"""""soil"""""""") will: improve predictive modeling of patients at risk for spread of esophageal cancer;identify novel targets for future chemopreventive and therapeutic agents;and serve as a model to study risk factors for site-specific metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA132892-03
Application #
7921049
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2008-09-26
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
3
Fiscal Year
2010
Total Cost
$135,351
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Shen, S; Araujo, J L; Altorki, N K et al. (2017) Variation by stage in the effects of prediagnosis weight loss on mortality in a prospective cohort of esophageal cancer patients. Dis Esophagus 30:1-7
Araujo, James L; Altorki, Nasser K; Sonett, Joshua R et al. (2016) Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients. Therap Adv Gastroenterol 9:806-814
Freedberg, Daniel E; Salmasian, Hojjat; Abrams, Julian A et al. (2015) Orders for intravenous proton pump inhibitors after implementation of an electronic alert. JAMA Intern Med 175:452-4
Sharaiha, Reem Z; Freedberg, Daniel E; Abrams, Julian A et al. (2014) Cost-effectiveness of chemoprevention with proton pump inhibitors in Barrett's esophagus. Dig Dis Sci 59:1222-30
Fudman, David I; Lightdale, Charles J; Poneros, John M et al. (2014) Positive correlation between endoscopist radiofrequency ablation volume and response rates in Barrett's esophagus. Gastrointest Endosc 80:71-7
Gupta, Milli; Iyer, Prasad G; Lutzke, Lori et al. (2013) Recurrence of esophageal intestinal metaplasia after endoscopic mucosal resection and radiofrequency ablation of Barrett's esophagus: results from a US Multicenter Consortium. Gastroenterology 145:79-86.e1
Freedberg, Daniel E; Abrams, Julian A (2013) Clostridium difficile infection in the community: are proton pump inhibitors to blame? World J Gastroenterol 19:6710-3
Wani, Sachin; Abrams, Julian; Edmundowicz, Steven A et al. (2013) Endoscopic mucosal resection results in change of histologic diagnosis in Barrett's esophagus patients with visible and flat neoplasia: a multicenter cohort study. Dig Dis Sci 58:1703-9
Freedberg, Daniel E; Salmasian, Hojjat; Friedman, Carol et al. (2013) Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol 108:1794-801
Abrams, Julian A; Gonsalves, Lou; Neugut, Alfred I (2013) Diverging trends in the incidence of reflux-related and Helicobacter pylori-related gastric cardia cancer. J Clin Gastroenterol 47:322-7

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