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Thomas L. Vaughan, MD, MPH, BS |
Professor, Epidemiology
Dr. Vaughan is also the Head of the Program in Epidemiology at the Fred Hutchinson Cancer Research Center in Seattle, Washington.
Contact Information
Fred Hutchinson Cancer Research Center
Box 358080; Mailstop: M4-B874
1100 Fairview Ave N
P.O. Box 19024
Seattle, WA 98109-1024
Tel: 206-667-5134
Fax: 206-667-4787
http://www.fhcrc.org/
tvaughan@u.washington.edu
Research Interests
Dr. Vaughan's research interests include environmental and genetic factors in the causation of cancer. Examples include studies of occupational exposure to formaldehyde and wood dust in relation to lung and nasopharyngeal cancer, obesity and use of selected medications in the etiology of esophageal and gastric adenocarcinoma, and polymorphisms in biotransformation enzymes as risk factors for cancer of the nasopharynx, lung, esophagus, stomach, and kidney. He is also involved in a cohort study of persons with pre-cancerous lesions of the esophagus, in which cell cycle and genetic abnormalities are being used as intermediate markers to facilitate identifying environmental and host factors that increase risk of neoplastic progression (see Barrett's Esophagus Project).
For more information visit Dr. Vaughan's Research Site: http://research.tvaughan.org
Education
MD, University of Illinois 1978
MPH, Epidemiology, University of Washington 1983
BS, Chemical Engineering, Cornell University 1974
Projects
Etiology Of Cancers Of The Upper Gastrointestinal Tract And Respiratory System.
GI Cancers
Over the past 25 years, the incidence of adenocarcinoma of the esophagus among white males in the US has increased almost 10-fold. Rapid increases among females and African Americans also have been observed. This rapidly fatal cancer is becoming increasingly common in parts of western Europe as well. Esophageal adenocarcinoma is thought to develop in a series of potentially reversible steps, usually under conditions of chronic reflux. A substantial proportion, perhaps 10 - 20%, of those with chronic reflux develop a metaplastic epithelium (Barrett's esophagus). Those with metaplasia are thought to be at highest risk, estimated at 0.5 - 1% per year, of developing dysplasia and eventually adenocarcinoma. Paralleling the histopathological changes are a number of cell cycle and genetic abnormalities, resulting in increased genetic instability and eventually invasive cancer.
One focus of our research is the identification of the environmental and host factors that underlie this trend. In particular, we are examining factors that cause or exacerbate gastroesophageal reflux, which results in increased cellular proliferation in the esophageal epithelium, and factors that are directly or indirectly genotoxic. Reflux can be caused by conditions such as hiatal hernia and obesity, as well a diet high in fat intake. A number of common medications reduce lower esophageal sphincter pressure and also promote reflux. Factors that may increase the likelihood of DNA damage in the esophageal epithelial cells include byproducts formed during tobacco smoking, diets low in fruits and vegetables, low serum levels of antioxidants, and a refluxate containing bile acids. Determinants of genetic susceptibility to esophageal and gastric adenocarcinoma, e.g., enzymes involved in the biotransformation of xenobiotics, are also being investigated. Such genetic polymorphisms may interact with environmental factors, such as in tobacco smoke byproducts or diet, in modifying risk in the general population.
We have approached these research questions through a series of studies that have included population-based case-controls studies of cancer, community-based case-control studies of newly diagnosed Barrett's, and a long-standing cohort study of persons with Barrett's. Our eventual goal is to identify not only the major risk factors for esophageal adenocarcinoma, but the stage(s) of neoplastic progression at which they act. Such knowledge would be particularly helpful in designing primary and secondary prevention strategies.
Respiratory Cancers
Another major area of study in our research unit is occupational exposures in relation to risk of lung and upper respiratory cancers. One industry of particular importance in western Washington is the wood industry. This region encompasses virtually all aspects of the industry from the planting and harvesting of timber, its transformation into more useful shapes, the production of wood-based products such as plywood and particle board, and the incorporation of wood into final products, such as in construction and furniture manufacture. Common to all of these processes is, of course, wood dust, a known carcinogen of the nasal cavities. Through a series of population-based case-control studies, we are investigating the role of wood dust and formaldehyde (an animal carcinogen commonly used in the industry) in cancers of the nasal cavities, nasopharynx, larynx and lung. We are also investigating polymorphisms in biotransformation enzymes as determinants of susceptibility to lung and nasopharyngeal cancer.
Critical to all of the above epidemiologic studies are collaborations with laboratory-based investigators in the Division of Human Biology and the PHS Core Laboratory at the FHCRC, and the Center for Ecogenetics and Environmental Health in the Department of Environmental Health at the University of Washington.
Selected Publications
Vaughan TL. The Esophagus. Cancer Precursors: Epidemiology, Detection and Prevention. Franco EL, Rohan TE, eds. New York: Springer-Verlag, 2002, pp. 96‑116
Vaughan TL, Dong LM, Blount PL, Ayub K, Odze RD, Sanchez CA, Rabinovitch PS, Reid BJ. Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett's oesophagus: a prospective study. Lancet Oncology 2005;6:945-52.
Chao DL, Maley CC, Wu X, Farrow DC, Galipeau PC, Sanchez CA, Paulson TG, Rabinovitch PS, Reid BJ, Spitz MR, Vaughan TL. Mutagen sensitivity and neoplastic progression in patients with Barrett's esophagus. Cancer Epidemiology Biomarkers & Prevention 2006;15:1935-40.
Galipeau PC, Li X, Blount PL, Maley CC, Sanchez CA, Odze RD, Ayub K, Self SG, Rabinovitch PS, Vaughan TL, Reid BJ. NSAIDs Modulate Risk of CDKN2A, TP53, and DNA Content for Future Esophageal Adenocarcinoma: Barrett's Esophagus Prospective Cohort Study. PLoS Medicine 4(2), e67 doi:10.1371/ journal.pmed.0040067.
Edelstein ZR, Farrow DC, Bronner MP, Rosen SN, Vaughan TL. Central adiposity and risk of Barrett's esophagus. Gastroenterology, in press.
Links
For more information, you can go to the Community of Science Expertise
FHCRC Faculty Homepage - for center news and research projects