Obesity And Colorectal Cancer - Untangling The Link

(RTTNews) - Obesity is said to greatly increase the risk of colorectal cancer. Though a number of hypotheses have been proposed for the association between obesity and colorectal cancer, the link between the two has not been clearly understood up till now.

But all that is said to change because a research team led by investigators at Thomas Jefferson University has discovered a big clue as to why the risk of colorectal cancer is more in obese individuals.

In preclinical studies with mice, the researchers found that when fed with a high caloric diet, the expression of guanylin, a key hormone in the intestine, was turned off, leading to deactivation of tumor suppressor pathway. But upon genetic replacement of the lost hormone, the tumor suppressor pathway was turned back on, which in turn prevented cancer development, despite the mice being fed with excess calorie.

Based on the new findings, the researchers believe that *Linzess, an approved drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults, might prevent colorectal cancer in obese patients. And the reason behind their belief is Linzess is structurally related to the endogenous guanylin.

Commenting on the findings, the study's senior author, Scott Waldman, Chair of Pharmacology & Experimental Therapeutics at Sidney Kimmel Medical College of Thomas Jefferson University, said, "The hormone guanylin turns on its receptor, guanylyl cyclase C (GUCY2C), which regulates processes underlying regeneration of the intestinal epithelium. The guanylin hormone receptor acts as a growth-controlling tumor suppressor, and without the hormone, the receptor is silenced. When the receptor is silenced, the epithelium becomes dysfunctional, setting up the conditions for cancer development."

The findings are published in the journal Cancer Research.

*Linzess is marketed by Ironwood and Actavis in the United States.