TORONTO - Bariatric surgery has been a boon to obese patients hoping to shed significant pounds or to treat weight-related diabetes, but the downside is an increased risk of developing colon cancer. Now researchers believe they may know why.
The surgery significantly reduces the amount of food a person can eat by reconfiguring the digestive pathway. But by bypassing much of the stomach and small intestine, the food that is consumed isn't completely broken down when it reaches the large intestine, or colon.
And that appears to stimulate overproduction of a gut hormone that may spur the growth of polyps in the colon that have a propensity to become malignant, suggests Dr. Daniel Drucker, an endocrinologist at Mount Sinai Hospital in Toronto.
In studies in laboratory mice, a research team led by Drucker found the digestive hormone GLP-1 was "a pretty potent growth factor" for the intestine in the animals, as well as a catalyst for intestinal tumours in other lab mice specially bred to study colorectal cancer.
"If we gave the mice more GLP-1, they got more tumours," said Drucker, a senior scientist at the hospital's Lunenfeld-Tanenbaum Research Institute. "If we took away the GLP-1 receptor from those mice, genetically, they got fewer tumours.
"So this gets us pretty convinced that we're onto something."
The concern about colon cancer made headlines in 2013 when a Swedish-U.K. study of more than 77,000 obese patients showed that those who had undergone bariatric surgery had a 60 per cent increased risk of developing the malignancy compared with the general population.
Among people who had the surgery more than 10 years before the study's conclusion, the number of cancer cases was 200 per cent higher than what was expected for the population as a whole; obese subjects who had not had the operation had a 26 per cent higher risk of colon cancer than the general population, but that figure remained stable over time.
Since the risk of developing many other cancers fell with the weight-loss surgery, doctors were puzzled at the rise in colon cancer risk.
While Drucker is quick to point out that mice aren't humans, he said the animal studies go a long way in providing a biological explanation.
"So if you say under what conditions might a human find themselves with increased levels of GLP-1 and the risk for intestinal tumour formation, probably the best delineated situation is the condition of bariatric surgery," he said, explaining that patients have elevated levels of GLP-1, other digestive hormones and bile acids, which are all known to stimulate intestinal growth.
Calling bariatric surgery the best available treatment for obesity and Type 2 diabetes, Drucker said eligible patients shouldn't shy away from the operation but should ensure they have regular screening for colon cancer afterward.
"We're very conservative. We don't make clinical recommendations based on findings in mice," he stressed. "But we would say that given the already available data that patients with bariatric surgery might have an increased risk of colon cancer and our new findings providing an explanation for why that might happen — have your colonoscopies."
That's also the advice for those taking a class of drugs used for diabetes control that work by activating the GLP-1 receptor to increase insulin and decrease blood glucose.
"It's important to state that GLP-1 doesn't by itself ... cause intestinal tumours," said Drucker. "But what we believe is that if you already have a propensity to form a tumour — so if you had an intestinal polyp, which is very common — then we believe that the growth of that polyp would be increased if the levels of GLP-1 were elevated."
While the research, published Tuesday in the journal Cell Metabolism, needs to be replicated by other researchers and confirmed in humans, he said patients should discuss the potential link between increased GLP-1 and colon cancer with their doctors.
"No previous studies to date have linked long-term use of GLP-1-based drugs with increased rates of cancer; however, we think patients with a previous history, or increased risk, of colon cancer may not be ideally suited for these therapies."