By: Vivian Yuen

With the increase in chronic diseases and the decrease in infectious diseases, particularly in developing countries, obesity is of major concern. In fact, more than two-thirds of adults are considered either overweight or obese, while more than one-third is considered obese. Even more so, about six percent of the adult population suffer from extreme obesity. This obesity pandemic leads to severe health problems. Not only does obesity increase a person’s chances of sleep apnea, stroke, and heart attack, it also is a risk factor for colorectal cancer. Researchers have established a link between obesity, insulin resistance, and colorectal cancer.

In particular, type II diabetes plays a major role in the pathway between obesity and colorectal cancer. In type II diabetes, there is an excess of insulin due to the increased blood sugar levels. To clarify, insulin is a hormone released by the pancreas that lowers blood sugar levels. This excess of insulin causes insulin resistance, in which cells cannot respond to insulin, and thus, lower the blood sugar levels. Specifically, insulin resistance encourages an increase in free IGF-1 factors (insulin-like growth factor 1), which can result in excessive cell development and decreased cell death. Both of these results are hallmarks of cancer. Furthermore, people with type II diabetes and obesity have increased serum leptin levels, which may increase the chances of getting colorectal cancer. There is currently unclear evidence regarding whether an increased level of serum leptin actually promotes growth of cancer cells, but some research indicates that serum leptin levels influence the development of epithelial intestinal cells (cells on the surface of the small or large intestine).

There are several ways to measure the risk for colon cancer. Interestingly, byproducts of type II diabetes can indicate a risk of developing colorectal cancer. For example, type II diabetes results in an increase in C peptide levels in the bloodstream. C peptides are byproducts of insulin production, just as how heat is a byproduct of burning wood. According to some researchers, those with high levels of C peptides in their bloodstreams are three times more likely to develop colorectal cancer than those without. In addition, visceral abdominal tissue (tissue that stores fat)  is related to insulin resistance and potential onset of colorectal cancer. Visceral abdominal tissue is associated with waist circumference. Thus, some doctors recommend measuring waist circumference in order to assess the risk for colorectal cancer and potentially also using BMI (body mass index), although waist circumference may be a more accurate value.

An interesting investigation surrounding obesity and its links to colon cancer is surrounding the role of guanylyl cyclase in tumor development. Guanylyl cyclase is a receptor protein that, when activated, allows for intestinal epithelial cells to be active and regenerated. With obesity, the hormone, guanylin, may be missing so that it cannot activate guanylyl cyclase. Since guanylin is essential to ensuring that intestinal epithelial cells are doing their job, intestinal epithelial cells without guanylyl cyclase activation may be more susceptible to becoming cancer cells. In fact, about 80% of patients with severe obesity have inactivated guanylyl cyclase. One treatment that could potentially ensure that guanylyl cyclase is activated is the use of Linaclotide, which is normally used for constipation relief.

Because obesity is a factor in the development of colorectal cancer, it is important to pursue an active role in taking care of yourself. It is extremely important to be proactive. I would recommend you, if you are at risk for colorectal cancer due to obesity, to ask your doctor about any novel treatments (such as Linaclotide) that could play a role in preventing colorectal cancer, either directly or indirectly.

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