Mutations in two genes coding for the immune cytokines IL-2 and IL-13 increase the risk of cutaneous T-cell lymphoma (CTCL), researchers have found, while mutations in two other immune factors were found to protect against the cancer.
These insights shine new light on the mechanisms that allow cancerous T-cells to infiltrate the skin in this type of cancer, which, despite its frequency, remains poorly understood.
Studies suggest that immune factors, such as cytokines, are involved in the development of T-cell lymphoma affecting the skin, but few have explored whether inherited differences coding for the factors can impact disease risk.
Researchers at the Medical University of Gdansk in Poland explored the presence of nine small mutations in the genes of seven cytokines — IL-1 alpha, IL-2, IL-13, IL-10, IL-8, endothelin-1, and TNF-alpha — in a group of patients and controls.
Most genes were analyzed in 43 patients; endothelin-1 was analyzed in 60. The mean age of the patients was 60.7 years, with a slightly higher mean age of 62.7 in the endothelin-1 group.
Between 84 and 261 people, depending on the analyzed mutation, served as controls. All lacked a personal or family history of chronic skin diseases and/or a personal history of cancer.
One mutation in the IL-2 gene and one in the gene coding for IL-13 were more common among patients than controls. The risk of developing the lymphoma was 5.8 times higher for people carrying the IL-2 mutation, compared with those who without the gene variant. The risk for those with the IL-13 gene variant was 5.7 times higher.
Both mutations are known to cause significant gene activity, and IL-2 has been linked to autoimmune conditions and other cancers. IL-13 has mainly been studied in skin diseases.
One mutation in the TNF-alpha gene and one in the IL-10 gene were less common among patients. Having these genetic variants were protective against cutaneous T-cell lymphoma.
No other mutations could be linked to the disease.
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