Gastric bypass and other stomach-shrinking surgeries may be popular, but they’ve also been linked to an increased risk of colorectal cancer. Now, scientists at Mount Sinai Hospital in Toronto say the results of their new animal study might explain this complicated connection. Even more, they are raising the alarm about a new generation of weight-loss drugs that mimic the after-effects of these procedures.

Generally, weight loss surgeries have been linked to a decreased risk of many types of cancers. In part, this is due to the fact that obesity, in and of itself, increases the incidence of malignancies — removing excess weight, then, directly impacts a person's tumor risk. However, colon cancer is the single exception to this rule.

“A large nationwide retrospective cohort study of 15,905 obese subjects treated with bariatric surgery revealed a significantly increased incidence of colorectal cancer, relative to obese control subjects,” noted the authors in their study. In fact, as length of time since gastric bypass surgery increased, so did the incidence rate of colorectal cancer.

Why, though, should this be the case? These are the questions asked and answered by the research team conducting the current study.

The research team began by looking at different bile acids and hormones residing in the gut. While all of these chemicals aid digestion, some, including glucagon-like peptide-2 (GLP-2), also work as growth factor hormones, stimulating cell division within the intestines. Another hormone, glucagon-like peptide-1 (GLP-1), appeared to be similar to GLP-2 but its role was less clear. The research team designed an experiment using mice: What effect would increasing this hormone — or eliminating it completely — have on the mice?

Using genetic tools, the researchers demonstrated that increasing the activity of GLP-1 increased the incidence of intestinal tumors in mice; conversely, eliminating its action by deleting the GLP-1 receptor in mice decreased the number of tumors. "Our paper now raises the possibility that GLP-1 is an intestinal growth factor,” said Dr. Daniel Drucker, senior author and a professor at the University of Toronto.

So why should this be a problem? Drugs which elevate levels of GLP-1, GLP-2, and bile acids in humans are currently being developed by pharmacological scientists to treat diabetes and other metabolic diseases. Targeting the glucagon receptor, these experimental drugs would lead to increased levels of GLP-1, GLP-2, and bile acids circulating within the body. While so far only animal studies have been conducted, it’s natural to wonder what might happen if these drugs are given to humans.

"No previous studies to date have linked long-term use of GLP-1-based drugs with increased rates of cancer," said Drucker, who cautioned more research is needed to flesh out these results. "However, we think patients with a previous history, or increased risk, of colon cancer may not be ideally suited for these therapies."

While surgery or pills may be necessary in drastic circumstances, the safest way for most people to lose weight is through exercise and diet... simple, it seems, is always best.

Source: Koehler JA, Baggio LL, Yusta B, et al. GLP-1R Agonists Promote Normal and Neoplastic Intestinal Growth through Mechanisms Requiring Fgf7. Cell Metabolism. 2015.