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David C. Whitcomb 

Researchers Find Region Of Gene For Inherited Pancreatic Cancer

PITTSBURGH, February 28, 2002 — Researchers at the University of Pittsburgh School of Medicine, in collaboration with the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine have mapped the location of a gene associated with inherited pancreatic cancer, which accounts for about 10 percent of all such malignancies.

Study co-directors David C. WhitAcomb, M.D., Ph.D., director of the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh; Leonid Kruglyak, Ph.D., a Fred Hutchinson statistical geneticist; and Teresa Brentnall, M.D., a UW gastroenterologist report their findings in an early electronic edition of the April issue of the American Journal of Human Genetics.

The discovery marks the identification of the first genetic defect that is directly linked to pancreatic cancer. By locating the region of the mutation, researchers will now be able to sequence the gene, which has the potential to yield promising new insights into pancreatic cancer.

"By understanding the genetics of pancreatic cancer, we can begin to understand the mechanism by which the disease develops, availing new methods of how to detect, prevent and treat this deadly cancer," said Dr. Whitcomb, who is also director of the University of Pittsburgh Center for Genomic Sciences.

Pancreatic cancer is one of the most difficult cancers to treat in that it is undetectable by a physical exam, asymptomatic, and progresses quickly – most patients die within 6 months of diagnosis. These factors also limit the amount of data available for research, hindering significant advances in the understanding of the disease.

"Pancreatic cancer is a very aggressive cancer with extremely low survival rates," said Ronald B. Herberman, M.D., associate vice chancellor for research, health sciences at the University of Pittsburgh and director of the University of Pittsburgh Cancer Institute. "Until now, we have had very limited ability to identify people at high risk for this disease or to make the diagnosis of the disease before it has invaded the rest of the body. This discovery represents a significant finding that may permit identification of individuals at risk so that they can be monitored regularly, to detect the cancer when it can be treated while still in an early stage, which might substantially enhance the likelihood of survival."

Researchers were able to gather sufficient genetic data for this study through the cooperation of a large Northwestern family known in scientific communities as "Family X." Family X is the largest pancreatic cancer family ever studied. Twenty affected family members were studied; nine have died of the disease, including five out of six brothers. Dr. Brentnall has been working with Family X for more than seven years.

The DNA samples collected by Brentnall’s University of Washington group from Family X were genotyped by a team of researchers at the University of Pittsburgh, led by Dr. Whitcomb. The Pitt group sequenced DNA from hundreds of areas of the genome known to contain a high degree of genetic variability. This information was then sent to Kruglyak’s group at Fred Hutchinson, who, by using sophisticated computer software, were able to determine which genetic variations are always present in the family members with pancreatic cancer or its precursor, dysplasia.

Virtually every member of Family X with pancreatic cancer or its precursor was found to harbor a specific genetic marker on the long arm of chromosome 4, where the single-gene mutation responsible for pancreatic cancer is thought to exist. None of the unaffected family members inherited this marker, supporting the significance of the findings.

According to researchers, identifying these markers may lead to the discovery of a specific pancreatic cancer gene – a finding that will allow doctors to screen people for genetic risk for pancreatic cancer with a simple blood test.

Dr. Whitcomb stresses the importance of the collaborative effort that resulted in this advancement. "Those of us who are working with complex and mysterious medical problems like pancreatic cancer recognize that no independent physician or scientists can go from the bed to the bench and back again alone. It takes physician-scientist teamwork, as demonstrated here, to make the big breakthroughs."

Of the 29,000 Americans who this year will learn they have pancreatic cancer, all but 100 will die within 12 months of diagnosis. While pancreatic cancer is the fifth leading cause of cancer death in the United States, it is one of the least well-funded areas of cancer research.

Due to the limited knowledge about pancreatic cancer, researchers stress that patients seeking treatment for pancreatic cancer or who are looking to be screened for the disease should visit a center that specializes in pancreatic disorders such as the Digestive Disease Center at the University of Pittsburgh or the University of Washington.

Support for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Mental Health; the National Pancreas Foundation; the Lustgarten Foundation; the Center for Genomic Sciences, University of Pittsburgh; and the Chiron Corporation.

For more information on pancreatic cancer and other diseases of the pancreas, visit or the National Pancreas Foundation at

For more information about the University of Pittsburgh division of gastroenterology, hepatology and nutrition visit their website at

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