Underlying mechanism for increased risk now defined.
Numerous observational studies have identified that people with red hair, fair skin, and a tendancy to burn rather than tan are at an increased risk for developing melanoma. However, the underlying mechanism for this link was unknown. Researchers from Beth Israel Deaconess Medical Center and Boston University School of Medicine found that a mutation of MC1R, called MC1R-RHC, triggers a cancer-causing signaling pathway in redheads when they are exposed to UV radiation. MC1R protects against cancer by binding to a tumor suppressor gene called PTEN, the absence of which results in a stronger signal along the cancer-causing P13K/Akt pathway. The researchers found the MC1R-RHC mutation that occurs in redheads lacks this PTEN anti-tumor mechanism.
The researchers found that higher PI3K/Akt activity of pigment cells carrying the MC1R-RHC mutation not only boosted tumor growth in its own right, but also synchronized with a mutation in the BRAF gene that is found in 70% of human melanomas. The researchers concluded that redheads with MC1R mutations are more susceptible to UV-induced skin damage and are more than ten times more likely to develop melanoma than people who don't have fair skin and red hair.
Cao J, Wan, L, Hacker E, et al. MC1R is potent regulator of PTEN after UV exposure in melanocytes. Molecular Cell 2013; 22(4):409-422.