Calluses & Throat Cancer Relationship

I thought the article I read by Ana Sandoiu was interesting, and one I had never even suspected. We all develop calluses at one time or the other, but some calluses and corns can become severe and very inconvenient. In some rare cases, an extreme thickening of the skin is a symptom of a particular form of esophageal cancer. They are researching the link between foot calluses and cancer in mice and humans.

Putting too much pressure on the skin or subjecting it to excessive friction causes calluses. This thickening of the top layer of skin is our body’s way of protecting that skin underneath. However, some calluses can become severe enough that the hardened skin has to be removed with a razor. It is recommended by the American Podiatric Medical Association that those with diabetes or circulatory problems have their feet checked because the calluses can lead to more serious problems.

Queen Mary University of London in the United Kingdom has conducted new research that examines the link between keratin (the protein found in the outer layers of the skin that play a key role in forming calluses) and a form of esophageal cancer called tylosis. Tylosis affects more than 8,000 people in the U.K and causes severe thickening of the skin in the hands and feet. Tylosis is associated with an esophageal cancer risk of over 95% and referred to as tylosis with esophageal cancer (TOC).

Esophageal cancer in the U.S. ranks as the 11 th leading cause of death, which equates to almost 16,000 people that are estimated to have died from the disease in 2016. There are other research investigations on the link between tylosis, calluses and esophageal cancer, but this study focuses on a particular gene found to play a crucial role in thickening the skin.

Researchers used genetically modified mice to study the iRHOM2 gene and found it to control keratin expression that is linked to TOC. Some mice had the iRHOM2 gene removed and they developed a much thinner epidermis on their paws, compared to those mice that still had the gene. They also found reduced expression of keratin 16 (K16) in iRHOM2-free mice. K16 is a cytoskeletal scaffolding protein that can be found in abundance at the pressure-bearing points in the footpad of mammals. The K16 levels in humans with TOC were also examined and they found a similarly heightened expression of the protein. It suggests that the iRHOM2 gene does help to regulate K16 in both humans and mice, and that iRHOM2 has been identified as a regulator of K16. This is the first study that demonstrates that iRHOM2 binds to K16 and this interaction increases in TOC patients. Because K16 is highly expressed in disease states such as
epithelial cancers and inflammatory dermatoses, there might be a broader significance for the role of iRHOM2 in the pathophysiology of these disorders that still remains to be explored.

–Dr Fredda Branyon