Study Reveals Link Between Obesity and Colorectal Cancer Risk

New research has discovered the biological connection between obesity and an increased risk of colorectal cancer (CRC).

Prior studies have indicated that obese patients have a 50% higher risk of developing CRC than people who are lean.

While the relationship between obesity and the increased risk of CRC cancer had long been suspected, the latest study identified the drug linaclotide (Linzess) as a potential preventative treatment for obese CRC patients.

The FDA approved linaclotide in 2012 for the treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation.

Scott Waldman, MD, PhD, Chair of Pharmacology & Experimental Therapeutics, Sidney Kimmel Medical College of Thomas Jefferson University, found that in mice models, a high-calorie diet switched off a key hormone in the intestine leading to the tumor suppressor pathway to deactivate. Conversely, genetically replacing that hormone turned the tumor suppressor back on, thereby preventing cancer development.

The team found that obesity is associated with loss of the hormone guanylin, which is produced in the intestine's epithelium, the cells lining the organ. Deactivation of the guanylin gene is common in colorectal cancers in both humans and animals, so morbidly obese patients exhibit an 80% decrease in guanylin gene expression compared to lean people.

"These findings came as a surprise — we and many other researchers worldwide have been trying to disentangle obesity from development of colorectal cancer," said Waldman. "Calories sit in the middle of these two conditions, but the question of what they were doing has been one of the most perplexing and provocative questions in cancer research.”

Waldan concluded, "The beauty of our findings is that while we know the hormone is lost in the obese mice, its receptors are just sitting there waiting to be switched on. And this study demonstrates that if you can prevent hormone loss, you can also prevent tumor development. These findings suggest that a drug like linaclotide, which acts like guanylin, can activate GUCY2C tumor-suppressing receptors to prevent cancer in obese patients.”