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July 2016

Red Hair, Light Skin, and UV-Independent Risk for Melanoma Development in Humans

Author Affiliations
  • 1Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
JAMA Dermatol. 2016;152(7):751-753. doi:10.1001/jamadermatol.2016.0524

A key gene that regulates pigmentation in humans is the melanocortin-1-receptor gene (MC1R; OMIM 155555), which encodes a 7-transmembrane G-protein–coupled receptor that regulates adenosine 3′, 5′ cyclic monophosphate (cAMP) levels in melanocytes. MC1R is activated by melanocyte stimulating hormone (MSH), which is secreted by UV-irradiated keratinocytes in the “tanning” response.1MC1R loss of function is one means of generating light skin that likely facilitates vitamin D biosynthesis. This plausibly provided an evolutionary selective advantage in preventing lethal vitamin D deficiency at high latitudes. Negative selective pressure may have arisen at low latitudes (higher UV intensity) owing to photolysis of vital factors such as folate or potentially increased skin cancer risk in lightly pigmented individuals.

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