A protein that dwindles in response to obesity and a sedentary lifestyle may one day help doctors predict which people are at increased risk for pancreas cancer, new research by Dana-Farber Cancer Institute and collaborating researchers indicates.
In a report in the Aug. 15 issue of Cancer Research, the researchers observed that, in a large study group, people with the lowest blood levels of a protein called IGFBP-1 were twice as likely to develop pancreas cancer as those with higher levels. Though much work remains to determine if the protein -- whose acronym stands for insulin-like growth factor binding protein-1 -- is a reliable indicator of pancreas cancer risk, the finding adds to the scientific understanding of how the disease develops. 
"The levels of insulin and another circulating hormone, insulin-like growth factor or IGF, are modified by obesity and sedentary lifestyle, and there is evidence that these hormones may stimulate the growth of pancreas cancer cells," said the study's lead author, Brian Wolpin, MD, of Dana-Farber. "When IGF binds to proteins like IGFBP-1, there may be less IGF available to bind to pancreas cancer cells and promote their growth. We wanted to determine whether IGFBP-1 levels in the blood were linked to pancreas cancer risk".
The researchers measured circulating IGFBP-1 levels in a select group of participants in four large, ongoing health studies: the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. They collected blood samples from 573 participants and, four or more years later, checked IGFBP-1 levels in the samples of 144 people who developed pancreas cancer and 429 who did not.
They observed that the quarter of the group whose IGFBP-1 levels were lowest had twice the risk of developing pancreas cancer of those in the top three quarters. The connection became even stronger over time: Among cases diagnosed at least eight years after blood collection, those in the bottom quarter of IGFBP-1 levels had nearly three-and-a-half times the pancreas cancer risk of those in the upper quarters.
The risk may be elevated because higher amounts of IGFBP-1 are able to "soak up" more IGF, leaving less available to spur pancreas cancer cell growth, or because IGFBP-1 has some cancer-blocking properties of its own, said Wolpin, who is also an instructor in medicine at Harvard Medical School. Another possibility is that other molecules may be involved, for which IGFBP-1 acts as an intermediary.
"It's known that a variety of proteins are affected by obesity and sedentary lifestyle," he added. "Studies are exploring whether a subset of these may play a role in the risk of developing pancreas cancer. More research is also needed on how alterations in insulin and proteins in the IGF family alter the risk of this difficult disease".
Posted by: Sue Source
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