Pancreatic Cancer Surprisingly Slow to Arise: Study

WEDNESDAY Oct. 27, 2010 -- Pancreatic cancer takes much longer to develop than commonly thought, say researchers who found a lag time of at least a decade between the emergence of key mutations and the formation of the first cancer cells.

The finding may offer hope for someday catching and treating this often-fatal disease in its early stages, scientists say.

The study, published in the Oct. 28 issue of the journal Nature, also provides new insight into the genetics of pancreatic cancer.

"What's important about this study is that it's objective data in support of why everyone should be screened for pancreatic cancer and, more important, when they should be screened," said study co-author Dr. Christine Iacobuzio-Donahue.

"I think [the data] is a major step toward impacting the survival rate of pancreatic cancer," added Iacobuzio-Donahue, associate professor of pathology and oncology at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins School of Medicine in Baltimore, which led the multi-center study.

The researchers used tissue from seven patients who died of pancreatic cancer that had spread to other organs. First, they extracted the DNA from cancer cells in the tissue. Then they sequenced the DNA, which contains operating instructions for every type of cell in the body.

In every patient, the cancer had spread, or metastasized, from the pancreas to at least two other areas, most often the liver, lung and abdominal lining. Similar cell mutations were found in the main tumor in the pancreas and in those other areas.

The scientists also classified the types of mutations -- changes in a gene that occur before and after cancer spreads. Both types of mutations were found in the primary cancer in the pancreas, years before it was known that the cancer had spread.

Using mathematical models to track the cancer's progression, the team estimated it takes an average of 11.7 years for the first cancer-causing mutation in a pancreatic cell to become a full-fledged cancer cell.

It then takes another 6.8 years, on average, for that cell to develop into a plum-sized cancerous tumor, after which at least one tumor cell develops the ability to spread to other organs. Once the cell spreads, patients die an average of two and a half years later.

"The science [in the study] is exquisite," said Dr. J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society in Atlanta. "The researchers were able to make the point that what we know as cancer is really the end stage of a very long process."

In its early stages, cancer of the pancreas -- the gland that aids digestion and helps control blood sugar levels -- causes vague symptoms or none at all. That's why people are typically diagnosed after the cancer has spread beyond the pancreas, and why the disease is often fatal. This year, pancreatic cancer will cause about 36,800 deaths, according to the U.S. National Cancer Institute.

Because people with pancreatic cancer typically die within a year of diagnosis, it may seem as if this form of cancer progresses rapidly, said Iacobuzio-Donahue.

"But what we've learned is that it is actually a long, slow process, and metastasis happens at the very end, within the final two to three years. Before that time, there is a tremendous window of opportunity for screening," she said. "We just have to modify our screening methods to better diagnose people at an earlier time point."

In the future, new imaging techniques and blood tests will offer hope for early detection, the study noted. And just as people have a colonoscopy when they turn 50, "perhaps they should have an endoscopy of their upper gastrointestinal organs that includes an ultrasound of the pancreas," said Iacobuzio-Donahue. Screenings for colon and breast cancers are based on age and health history, rather than symptoms, she noted. "But we screen people for pancreatic cancer based on how they feel," she said. "And by the time they feel sick, it's too late."

Lichtenfeld, however, says it's "a bit optimistic" to suggest that current technologies, such as ultrasound, can diagnose pancreatic cancer early enough to make a difference. Another cancer with virtually no symptoms in its earlier stages -- ovarian cancer -- is not often found with ultrasound, he noted.

But "we're probably not far away" from the advanced screening techniques mentioned in the study, he said.

More information

To learn more about pancreatic cancer, visit the American Cancer Society.

Posted: October 2010


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