New hope for blood test to catch pancreatic cancer early
11 November 2013
A simple blood test to detect gene fragments unique to pancreatic cancer cells could be on the horizon following promising results in a small preliminary study at Johns Hopkins Medicine in the US.
An early test is important because at the moment pancreatic cancer is nearly always fatal as there is no way to detect the disease until the late stages and it has spread to other parts of the body. It has an overall five-year survival rate of less than 5% and has seen few improvements in survival over the last three decades.
Researchers were able to identify two genes, BNC1 and ADAMTS1, which together were detectable in 81% of blood samples from 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% of prostate cancers.
In pancreatic cancer cells, it appears that chemical alterations to the genes BNC1 and ADAMTS1 — modifications that alter the way the genes function without changing the underlying DNA sequence — silence the genes and prevent them from making their protein product, the role of which is not well-understood. These alterations are caused by the addition of a molecule called a methyl group to the DNA.
Using a very sensitive method called Methylation on Beads (MOB) developed by Dr Jeff Tza-Huei Wang, a professor at the Whiting School of Engineering at Johns Hopkins, the researchers were able to identify in the blood the smallest strands of DNA of those two genes with their added methyl groups. The technique uses magnetic nanoparticles to attach to the few gene fragments being shed by the tumours, which are enough to signal the presence of pancreatic cancer in the body, the researchers found.
The researchers found the genes BNC1 and ADAMTS1 in 97% 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.
“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 MD, an associate professor of surgery, oncology and urology at the Johns Hopkins University School of Medicine and leader of the study published 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.”
Ahuja says the practical value of any blood test for cancer markers depends critically on its sensitivity, meaning the proportion of tumours it detects, and its specificity, meaning how many of the positive results are false alarms. The specificity of this new pair of markers is 85%, meaning 15% would be false alarms. Ahuja says she hopes further research will help refine the test, possibly by adding another gene or two, in order to go over 90% in both sensitivity and specificity.
Ahuja also cautions that her team still needs to duplicate the results in a larger sample of tumours, 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 developing the disease, such as those with a family history of pancreatic cancer, a previous case of pancreatitis, long-term smokers or people with the BRCA gene mutations, which are linked to breast, ovarian and pancreatic cancers. She hopes a commercial blood test might one day only cost US$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.
People who test positive will likely undergo CT scanning and/or endoscopic ultrasound tests — whereby a tube is placed down the throat into the stomach to image the pancreas — to search for the cancer. Surgery to remove it would presumably have a better chance of curing the disease owing to its small size and early stage.
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