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Hutchinson Center: Kristen Lidke Woodward (206) 667-5095
University of Washington: Laurie McHale (206)543-3620

FOR IMMEDIATE RELEASE
Thursday, Sept. 10, 1998

Hutchinson Center to Lead $8 Million Study of Colorectal and Pancreatic Cancers

Today at the White House, first lady Hillary Rodham Clinton announced that the Fred Hutchinson Cancer Research Center in Seattle has been selected to lead an $8 million, four-year investigation into the causes, prevention and early detection of colorectal and pancreatic cancers.
     The grant announcement was made earlier this afternoon during a special White House event at which the first lady underscored her support for the prevention and early detection of colorectal cancer. In addition to Mrs. Clinton, a variety of speakers were featured, including NBC "Today" show co-anchor Katie Couric (who lost her husband to colon cancer earlier this year) and Donna Shalala, secretary of Health and Human Services.
     The Seattle Gastrointestinal Program Project, funded by the National Cancer Institute, will support three studies involving more than two dozen investigators at the Hutchinson Center, the University of Washington, Group Health Cooperative, Veterans Affairs Puget Sound Health Care System and Virginia Mason Medical Center.
     The researchers will study people with pancreatitis and chronic ulcerative colitis inflammatory diseases that are a major risk factor for the development of pancreatic and colorectal cancers, respectively. Patient recruitment, which will involve nearly 1,000 Seattle-area residents, will begin by the end of the year.
     "People with these inflammatory disorders face up to 20 times the risk of going on to develop cancer," says principal investigator John D. Potter, M.D., Ph.D., director of the Cancer Prevention Research Program in the Hutchinson Center's Division of Public Health Sciences. "One of the reasons we have chosen to study these two cancers is because they are major public health problems; colorectal cancer because of its very high incidence and its relative preventibility, pancreas cancer because of its very high death rate," says Potter, also a professor of epidemiology at the UW.
     Indeed, some 150,000 new cases of colorectal cancer are diagnosed annually in the United States, where it is the third most common type of cancer in men and women. Pancreatic cancer, while less common, is almost uniformly fatal; the survival rate is about 5 percent, and most people die within four months of diagnosis.
     Understanding what causes the progression of these inflammatory diseases to malignancy will be critical to designing effective strategies to prevent or delay the onset of these cancers. This knowledge also could lead to the development of screening tests for pancreatic cancer (currently there are none) and more sensitive, less invasive early detection methods for colon cancer than those currently available, such as fecal-occult blood testing and endoscopy.
     Researchers know that colorectal and pancreatic cancers, like all malignancies, are genetic diseases that arise when key regulatory genes in a cell become damaged and either stop working or functioning correctly. When these genes malfunction, a cell can gain the ability to act independently, dividing on its own unregulated schedule and putting a person at risk for cancer.
     Though scientists already have discovered a great deal about how some of these key genes work, they still know very little about what actually causes the damage.
     The working hypothesis behind the Seattle GI Program Project is that cancer growth is triggered by oxidative damage to our genetic code, or DNA. This occurs when a highly reactive byproduct of the oxygen we breathe free-radical molecules gradually damage, or mutate, our DNA. One theory is that cancer arises when our damaged cells either fail to repair themselves or fail to self-destruct a process called apoptosis, which normally is the fate of damaged cells.
     "Some leaders in the field call these damaged cells `the living dead,' because they go on reproducing even though, under normal circumstances, they wouldn't," Potter says. "A lot of us think that these are the key players in the development of cancer. One of our hopes for this study is to find clear evidence that this is what's really going on."
     Below are brief descriptions of the three studies being undertaken by the consortium, all of which seek to apply the insights of laboratory research to prevent, detect and better understand the causes of pancreatic and colorectal cancer in humans:
     Project 1: This study is looking into the role of oxidative damage in the progression of pancreatitis to pancreatic cancer. Tissue studied will be taken during endoscopic examination of the pancreatic ducts a routine part of diagnosis for pancreatitis. This study also will gauge the effectiveness of antioxidants in treating pancreatitis and preventing its escalation toward malignancy. About 150 pancreatitis patients will be recruited for this study, the majority from Group Health Cooperative. Leader: Richard H. Bell Jr., M.D., professor and vice chairman of the UW Department of Surgery and service line leader in Surgical and Perioperative Care, VA Puget Sound Health Care System. Co-leaders: Teresa Brentnall, M.D., acting assistant professor of medicine in the UW Division of Gastroenterology; and Lawrence Loeb, M.D., Ph.D., professor of pathology and of biochemistry at UW.
     Project 2: This study is very similar in concept and design to Project 1, except the focus will be on the role of oxidative damage in chronic ulcerative colitis and its progression to colorectal cancer. The effectiveness of a chemopreventive approach (using complex mixtures of food-derived antioxidants) in preventing or reversing disease progression also will be studied. About 30 ulcerative colitis patients from the University of Washington will be recruited for this study. Leader: Teresa Brentnall, M.D., (also co-leader of Project 1, above). Co-leaders: Mary Bronner, M.D., assistant professor and director of the DNA Probe Laboratory in the UW Department of Pathology; and UW pathology professor Peter Rabinovitch, M.D., Ph.D.
     Project 3: The goal of this study is to develop a low-cost, minimally invasive and sensitive screening tool for colon cancer. This study will attempt to measure some of the early pathologic changes in the lining of the colon and rectum to try and discriminate those at high and low risk of colorectal cancer. Tiny snippets of tissue taken during colonoscopy will be tested for evidence of oxidative damage biomarkers that may be associated with greater cancer risk such as changes in cell death and cell division. Specifically, researchers hope to determine whether a rectal biopsy could be used to screen for malignancies throughout the entire colon, based on the presence of certain biomarkers in the rectal tissue. If so, rectal biopsy (less costly and invasive than colonoscopy) may one day be used as a front-line screening tool for colon cancer. Approximately 800 colonoscopy patients will be recruited for this study, most from Group Health. Leader: John Potter, M.D., Ph.D., (also principal investigator of the Program Project). Co-leader: Polly A. Newcomb, Ph.D., member in the Hutchinson Center's Cancer Prevention Research Program, Division of Public Health Sciences.
     Potter credits colleague David Hockenbery, M.D., an assistant member in the Hutchinson Center's divisions of Clinical Research and Molecular Medicine and an associate professor of immunology and of medicine at UW, for being a catalyst in the formation of the group. "He was key in linking the clinical researchers with the basic scientists, and he'll act as a consultant on the project," he says.
     The Hutchinson Center is one of 35 National Cancer Institute-designated comprehensive cancer centers and ranks first in the nation in total federal funding for cancer research. In fiscal year 1997, The Hutch received more than $54 million in research grants from the NCI.

(NOTE: Replays of a live broadcast of the White House event can be seen on the Hutchinson Center's web site: www.fhcrc.org. Links can be found in the "Center News" and "Press Relations" sections of the site.)
    
    

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