As a freckle-faced redhead, I’m constantly reminded to wear a hat and to slather myself with sunscreen. Even strangers on the street warn me to stay out of the sun. Unfortunately, I’m now faced with the fact that even these safeguards may not be enough to protect me from skin cancer. New research in Nature suggests redheads may be genetically predisposed to melanoma, even if they never see a ray of UV light.

Pigment production is controlled by a gene called MC1R, and is responsible for the veritable rainbow of human complexions. The relative abundance of two pigments (pheomelanin and eumelanin) determines hair and skin color. In dark-skinned individuals with dark hair, MC1R activity leads to production of large amounts of eumelanin, compared to relatively small amounts of pheomelanin. Redheads with fair skin have mutations that disrupt the MC1R pathway, producing more pheomelanin than eumelanin. We’ve long known that redheads are at a high risk of sun-induced skin cancer, but the researchers behind this study wondered whether something about pheomelanin itself may contribute to the high incidence of melanoma in those with fair skin, even in the absence of cancer-causing UV exposure.

To investigate this potential link, the researchers used strains of mice with pigment profiles that mimicked various human complexions. Like humans with dark skin, control mice with black coats had an intact MC1R gene and produced much more eumelanin than pheomelanin. A second strain of mice, with a mutated MC1R gene, had reddish coats and had a much higher pheomelanin to eumelanin ratio. The third strain of mice was albino, which produced no pigment at all.

Mice from each strain were then crossed with mice with a mutation called BRAFV600E, which has been implicated in the development of malignant melanoma. (Up to 60 percent of all human patients with melanoma have this mutation.) The researchers then monitored the mice over time, carefully making sure that they were not exposed to UV light or any other environmental cancer-causing agents.

Black and albino mice that carried the BRAFV600E mutation developed melanoma at a very low rate, and only after a long period of time. However, more than 50 percent of the red mice with the same mutation developed melanoma after just one year.

To determine whether pheomelanin itself was behind this extremely high incidence of cancer, the researchers halted pigment production in red mice by introducing an albino allele. After a year, melanoma incidence in these mice was no different than those in the black or albino mice, suggesting that something about the pheomelanin pathway itself may play a role in UV-independent melanoma.

It turns out that redheads may be vulnerable to more oxidative DNA damage, even if they stay out of the sun: the researchers found several indicators of DNA damage—lipid peroxide and two cyclopurine levels—were much higher in mice that produced large amounts of pheomelanin. This DNA damage, in turn, contributes to the development of malignant melanoma.

It has long been known that UV radiation causes skin cancer, especially in fair-skinned redheads, but these results suggest that even redheads that stay out of the sun aren’t completely protected from melanoma. The same pigment pathway that gives them their fiery hair and freckles may actually damage their DNA and lead to melanoma, without any help from the sun’s rays. Unfortunately, it’s still unclear how to stop this damage. Experts advise redheads to visit the dermatologist regularly, and suggest that increasing oral antioxidant intake might decrease melanoma risk.

But, of course, don’t throw away that sunscreen; sun exposure is still the leading risk factor for skin cancer, in both redheads and others.

Nature, 2012. DOI: 10.1038/nature11624 (About DOIs).