UW News

March 14, 2002

Location of pancreatic cancer genetic defect found

Researchers at the UW School of Medicine and Fred Hutchinson Cancer Research Center, in collaboration with investigators at the University of Pittsburgh School of Medicine, have mapped the location of a gene associated with inherited pancreatic cancer.


UWMC gastroenterologist Dr. Teresa Brentnall; Dr. Leonid Kruglyak, a Fred Hutchinson statistical geneticist; and Dr. David C. Whitcomb, head of gastroenterology at Pittsburgh; and colleagues report their findings in the early electronic edition of the April issue of the American Journal of Human Genetics.


Having found the gene’s neighborhood, in a fairly large region called 4q32-34, the researchers now aim to close in on its specific address.


“There are about 100 genes in the region, a fair amount of data to sift through. I would think we’d probably have the gene sequenced within a year, but ultimately it’s truly a matter of luck,” said Brentnall, UW associate professor of medicine and pathology.


Finding the gene promises to shed new light on how pancreatic cancer develops, ultimately opening new avenues for preventing, detecting and treating this particularly deadly malignancy, which has, until now, largely remained an enigma in cancer research.


“You can’t touch it or feel it. You can’t find it on physical exam. The cancer is asymptomatic, strikes later in life and is rapidly lethal — most people die within six months of diagnosis,” Brentnall said. “Such factors have impeded the collection of material for study and have hampered our ability to understand the natural history of the disease, resulting in very little headway in the past hundred years.


“This finding will open up an area that was previously a black box,” she said.


Gathering enough genetic data to help pry open that box was made possible, first and foremost, by the cooperation of a large Northwestern clan widely known in scientific circles as “Family X,” the largest pancreatic-cancer family ever studied. (The family chooses to remain anonymous.)


“What makes this family so remarkable is that it is extremely large and has a very high incidence of early onset pancreatic cancer. Most family members have been diagnosed in their mid-40s and the age of diagnosis just keeps getting younger with every generation,” said Brentnall, who has been working with Family X, scientifically and clinically, for more than seven years.


Another crucial aid to data collection was the development at the UW of a pioneering pancreatic-cancer screening program for high-risk individuals, which uses endoscopic imaging techniques to help detect precancerous changes in the pancreas while there’s still time to intervene surgically — before cancer develops.


All members of Family X who’ve had abnormalities detected endoscopically — and precancerous changes confirmed through tissue biopsy — have opted for preventive removal of the pancreas, an organ that contains insulin-producing cells key to blood-sugar regulation. The organ also produces enzymes that aid digestion.


When the pancreas is removed, a person must take insulin and digestive enzymes for the rest of their lives to compensate for the organ’s removal. Although all of these patients become insulin-dependent diabetics, they can enjoy long, productive lives, said Brentnall, founder and director of UW’s pancreatic-cancer surveillance program, the first of its kind in the nation. The program currently serves 35 patients from more than a dozen families.