A person's skin pigment, which determines hair colour and skin tone, is influenced by the melanocortin-1 (MC1R) gene receptor, researchers said.
    
Researchers from Beth Israel Deaconess Medical Center (BIDMC) and Boston University School of Medicine (BUSM) have discovered that the same MC1R mutation responsible for the red hair phenotype also promotes an important cancer-causing pathway.
    
The new findings help to explain the molecular mechanisms that underlie redheads' well-known risk of developing melanoma, providing new insights for treating and preventing this dangerous type of skin cancer.
    
Melanoma is the least common but the most lethal of skin cancers. Accounting for 75 percent of all skin-cancer deaths, melanoma originates in pigment-producing skin cells called melanocytes, researchers said.
    
Melanoma is believed to be a multi-step process (melanomagenesis) of genetic mutations that increase cell proliferation, cell differentiation and cell death and increase an individual's susceptibility to ultraviolet (UV) radiation. Two types of UV radiation - UVA and UVB – can mutate DNA in skin cells and lead to melanoma.
    
"We have demonstrated that the mutation MC1R-RHC promotes the PI3K/Akt signaling pathway when a red-haired individual is exposed to UV radiation," said co-senior author Wenyi Wei, Associate Professor of Pathology at Harvard Medical School.
    
PI3K/Akt is a well-known cancer-causing pathway, implicated in breast cancer, ovarian cancer and lung cancer.
    
Previous work by the study's co-senior author Rutao Cui, demonstrated that MC1R plays a key role in protecting melanocytes from UV-induced DNA damage. In this current study, Wei and Cui wanted to find out how this was happening.
    
Led by co-first authors, Lixin Wan, and Juxiang Cao, the scientific team embarked on a series of experiments in both cell cultures and mouse models.
    
Their experiments showed that in normal circumstances, MC1R was binding to PTEN, a well-known tumour suppressor gene. PTEN acts to safeguard against cancer, without PTEN, the end result is elevated signaling in the cancer-causing P13K/Akt pathway.
    
Researchers demonstrated that MC1R-RHC mutations found in red-haired individuals lacked this protective mechanism.
    
"As a result, upon UVB exposure, we saw an increased destruction of PTEN in the mutated pigment cells," said Wei.

(Agencies)

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