Thick Skin Over Palms and Soles Linked to Esophageal Cancer

Highlights:

Tylosis is an inherited condition characterized by thickened skin over the palms and soles
It is associated with an increased incidence of esophageal cancer
‘Gain of function’ mutation of iRHOM2 gene seen in Tylosis
Targeting iRHOM2 gene might lead to newer treatment options in esophageal cancer

Esophageal cancer might be related to increased thickness of palms and soles, according to research conducted by Queen Mary University of London. Esophageal cancer affects more than 8000 persons in the UK annually.

During the study, the research team found that humans with increased expression of the iRHOM2 gene had markedly thickened skin over their palms and soles and interestingly were found to be at an increased risk of developing esophageal cancer.

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‘Targeting iRHOM2 gene associated with thickening of skin over palms and soles could pave the way for new therapy for esophageal cancer.’

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On the contrary, knocking off iRHOM2 gene in mice was shown to cause abnormally thin skin over their paws.

What Causes Thickened Skin over Palms and Soles?

The increased thickness of the skin over the palms and soles is due to the abundance of a protein called keratin.

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The palms and soles are uniquely adapted to withstand physical stress due to a variety of day-to-day activities such as housework, walking and running. This strength and resilience is provided by the protein keratin which forms a framework inside the cells of the skin. The skin of the palms and soles consist of a type of keratin called K16. K16 is also formed in increased amounts during wound healing processes and in inflammatory conditions of the skin.

Interestingly, K16 is a biomarker of a variety of cancer called squamous cell cancer seen in the esophagus, cervix and nasopharynx.

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What is Tylosis?

Tylosis is a rare inherited disorder characterized by extremely thick skin over the palms and soles due to increased deposition of keratin. Persons suffering from this condition also have an increased risk of developing squamous cell cancer of the esophagus.

The thickening of the palms and soles begins by around 10 years of age, the soles being more affected than the palms. Affected individuals develop esophageal cancer affecting the lower 2/3rds by 45 years of age. Tylosis Associated Esophageal Cancer (TOC) and iRHOM2 Gene Mutations Studies have shown that K16 is regulated by the iRHOM2 gene. In Tylosis with Esophageal Cancer (TOC), there is mutation of the iRHOM2 gene leading to its ‘gain of function.’ This in turn causes increased expression of K16 protein.

A loss of iRHOM2 is associated with decreased expression of K16 and thinning of the footpads of mice.

The above findings outline an important role for iRHOM2 gene in regulating the epithelial cell response to physical stress and why persons who indulge in hard physical work involving hands have thickened and callused palms.

Conclusions From the Study

Targeting the iRHOM2 gene could open up new treatment options in esophageal cancer. Further research on iRHOM2 gene mutation might offer new insights into skin conditions such as psoriasis and skin cancer.

References:

RHBDF2 Mutations Are Associated with Tylosis, a Familial Esophageal Cancer Syndrome - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276661/)