Colon cancer may be driven in part by hormone loss

Researchers from Thomas Jefferson University (PA, USA) have reported the first instance of a cancer developing due to a lack of hormone. The research, published recently in Cancer, Epidemiology, Biomarkers & Prevention, suggests that human colon cells may become cancerous when they lose the ability to produce the hormone guanylin.

The study examined colon tumor samples from 281 patients and compared these to surrounding healthy colon tissue. The team measured the number of mRNAs for guanylin contained in each cell and found that guanylin production decreased by 100–1000 times in more than 85% of colon cancer samples. Verification of these results involved staining the tissue samples for guanylin production and no guanylin was detected in the cancerous samples.

“The fact that the vast majority of cancers stop producing this hormone leads us to believe that guanylin may be driving the growth of the tumors,” explained senior author Scott Waldman (Thomas Jefferson University, PA, USA).

Guanylin is known to be a locally-acting hormone that is produced by the cells it acts upon. It activates the receptor GUCY2C, which is responsible for replenishing the skin cells that line the gut and maintaining their overall function. Without accurate control of the signals regulating this replenishment, aberrant cell division is more likely to occur, which in turn may lead to cancer.

When guanylin levels decrease, colon cells produce more GUCY2C in order to maximize the detection of signals from outside of the cell. Therefore, colon cancers will often display high numbers of GUCY2C receptors.

Although other cancer types have been found to develop in response to hormones, such as testosterone or estrogen, this is the first instance of a cancer being driven by the lack of a hormone. Another notable finding from the investigation was that individuals over 50 years of age produced significantly lower levels of guanylin in their colon cells, which could account for the increased risk of colon cancer in this age group.

Colon cancer is currently the second leading cause of cancer mortality for both men and women and Waldman emphasized the significance of these findings: “We could prevent colon cancer by giving patients hormone-replacement therapy with guanylin.”

Follow on research is essential, according to Waldman: “The next steps are to test whether hormone replacement can prevent colon cancer development and/or growth in mice, which could then be followed by tests in humans.” Meanwhile, the team is investigating the mechanisms behind guanylin’s role in maintaining colon cell health.

Source: Thomas Jefferson University press release