Researchers from the University of Wisconsin-Madison have identified four blood-based protein markers associated with the pre-cancerous forms of colon cancer that are most likely to develop into disease, according to a new report published in the Proceedings of the National Academy of Sciences.
The scientists expect their findings will ultimately lead to a blood test for the cancer, adding a method to help increase screening rates while reducing overtreatment.
The study’s senior author, Bill Dove, said: ‘This study is the first peek at the possibility that there will be blood markers for a minimally-invasive procedure that can reduce over-diagnosis. They do exist.’
The gold standard for colon cancer screening is currently optical colonoscopy, where patients must complete a day-long prep to empty their bowels before undergoing an invasive procedure – factors that contribute to low screening compliance.
When a doctor finds growths in the colon during the procedure, in most cases, they will remove those polyps and have them analysed as either cancerous or benign (which are further divided into high or low-risk of becoming cancerous).
Another screening option, computed tomographic colonography, requires a similar bowel prep but provides a non-invasive image of the colon. This method requires a follow-up optical colonoscopy and polyp removal if it reveals an area of concern. In many low-risk cases, physicians will recommend a monitoring approach instead.
In studies of patients undergoing computed tomographic colonoscopy, researchers have found that the majority of small polyps detected during screening will never become cancerous and treating them is unnecessary.
To cut down on over-treatment, the researchers in this study looked for proteins that are elevated in the blood of only those patients who have growing polyps or cancerous polyps but not elevated in patients with non-growing polyps or no polyps at all.
They examined blood samples from 90 optical colonoscopy patients – split into groups of no, low- or high-risk pre-cancerous polyps – and 31 computed tomographic colonography patients who were monitored without polyp removal.
Next, the scientists selected 19 proteins they previously found to be elevated in rodent models of colon cancer and performed a technique known as mass spectrometry to measure protein concentrations in the patients’ blood.
Because they already knew the results of each patients’ colonoscopy, the researchers could correlate patient blood marker findings with their outcomes, allowing them to identify which markers, if any, are specifically associated with growing or cancerous polyps.
Lead study author Melanie Ivancic found four elevated proteins that are associated with early colon cancer in the patients studied: ‘There’s good evidence they’re being conserved in early disease in humans,’ Dove says. ‘We didn’t expect we could find blood markers for such small, early, pre-malignant polyps in humans, but we did.’
‘We believe success may come from combining multiple strategies that are statistically independent from each other- called ‘orthogonality. Our study reports markers that, though modest in power, may contribute to orthogonal quantitative marker panels to detect the growing pre-malignant adenoma in the colon.’