NIEHS Grant F30ES020663
People with pale skin, red hair, freckles, and an inability to tan have the highest risk of developing melanoma, the most dangerous type of skin cancer. A study supported by the NIEHS identifies a new mechanism that helps explain this risk and provides information that might aid in protecting people with the highest melanoma risk.
Pheomelanin, the predominant skin pigment for people with red hair and fair skin, is less protective against ultraviolet (UV) radiation damage than the eumelanin found in people with dark skin and hair. However, studies indicate that reduced UV protection may not fully explain why individuals with red hair and freckles are more at risk for melanoma. To find out more about the role of pheomelanin in melanoma risk, the researchers conducted an animal study involving dark-colored mice with the typical gene variant for a predominance of eumelanin and mice with the variant that produces red hair and fair skin in humans.
Even without UV exposure, the red hair/fair skin mice had a greater number of invasive melanomas than the other mice, suggesting that the pheomelanin pigment itself was involved in melanoma. The researchers then tested mice with no skin pigment (albino), and these mice developed less melanoma than the red hair/fair skin mice. In addition, the red hair/fair skin mice had significantly greater oxidative DNA and lipid damage than the albino mice. The study findings suggest that in the absence of UV exposure, the pheomelanin pigment contributes to melanoma via oxidative damage. The researchers say protection from ultraviolet radiation remains important, but additional strategies may be needed to achieve the best melanoma prevention.
Citation: Mitra D, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA, Robinson KC, Devi SP, Vanover JC, D'Orazio JA, McMahon M, Bosenberg MW, Haigis KM, Haber DA, Wang Y, Fisher DE. 2012. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature; 5;491(7424):449-453.