A simple new blood test may reveal early signs of pancreatic cancer, a disease that now is nearly always fatal because it isn’t usually discovered until it has spread.
The findings of a small preliminary study, if confirmed, could be an important step toward reducing mortality from the cancer, researchers say. The disease has a five-year survival rate of less than 5 percent; there have been few improvements in survival over the past three decades.
“We have mammograms to screen for breast cancer and colonoscopies for colon cancer, but we have had nothing to help us screen for pancreatic cancer,” says Nita Ahuja, associate professor of surgery, oncology and urology at the Johns Hopkins University School of Medicine. She led the study described online this month in the journal Clinical Cancer Research.
“While far from perfect, we think we have found an early detection marker for pancreatic cancer that may allow us to locate and attack the disease at a much earlier stage than we usually do,” she says.
Ahuja and her colleagues were able to identify two genes, BNC1 and ADAMTS1, which together were detectable in 81 percent of blood samples from 42 people with early-stage pancreatic cancer, but not in patients without the disease or in patients with a history of pancreatitis, a risk factor for pancreatic cancer.
By contrast, the commonly used PSA antigen test for prostate cancer only picks up about 20 percent of prostate cancers.
Ahuja’s team found that in pancreatic cancer cells, chemical alterations to BNC1 and ADAMTS1—epigenetic modifications that alter the way the genes function without changing the underlying DNA sequence—prevent the genes from making their protein product. These alterations are caused by the addition of a methyl group to the DNA.
Using a very sensitive method developed by Johns Hopkins engineers, the researchers were able to find in the blood even the smallest strands of DNA of those two genes with their added methyl groups.
The technique uses nanoparticle magnets to latch onto the few molecules being shed by the tumors, which are enough to signal the presence of pancreatic cancer in the body, the researchers found.
Researchers say they found BNC1 and ADAMTS1 in 97 percent of tissues from early-stage invasive pancreatic cancers. Surgery is the best chance for survival in pancreatic cancer, because radiation and chemotherapy are not very effective against it. The smaller the cancer—the earlier it is detected—the more likely surgery will be successful and the patient will survive.
Fewer false alarms
Ahuja says the practical value of any blood test for cancer markers will depend on both its sensitivity, or the proportion of tumors it detects, and its specificity, or how many positive results are false alarms.
The specificity of this new pair of markers is 85 percent, meaning 15 percent would be false. Ahuja says she hopes further research will help refine the test, possibly by adding another gene or two, in order to go over 90 percent in both sensitivity and specificity.
Ahuja also cautions that her team needs to duplicate the results in a larger sample of tumors, but is encouraged by the results so far. She says she doesn’t envision the blood test as a means of screening the general population, the way mammograms and colonoscopies are used to find early breast and colon cancers.
Instead, she imagines it would be best used in people at high risk for the disease, such as those with a family history of pancreatic cancer or a previous case of pancreatitis, or those who are long-term smokers or people with the BRCA gene mutations, which are linked to breast, ovarian, and pancreatic cancers.
“You have to optimize your medical resources,” says Ahuja, who hopes a commercial blood test might one day only cost $50.
She also notes that once BNC1 and ADAMTS1 are identified in a patient’s blood, further tests will be needed to locate an actual cancer. Surgery to remove it would presumably have a better chance of curing the disease owing to its small size and early stage.
The National Cancer Institute and National Institute of Environmental Health Sciences, the American College of Surgeons/Society of University Surgeons Career Development Award, the Lustgarten Foundation, the Miriam and Sheldon G. Adelson Medical Research Foundation, and the National R&D program through the Dongnam Institute of Radiological and Medical Sciences funded by the Korean Ministry of Education, Science and Technology supported the work.
Source: Johns Hopkins University