Redheads Carry Melanoma Risk Independent of Sun Exposure

Photo Credit: Mass General Cancer Center

David E. Fisher, MD, PhD
Chief, Dermatology Service, Massachusetts General Hospital

Director, Melanoma Program, Massachusetts General Hospital Cancer Center

Director, Cutaneous Biology Research Center, Massachusetts General Hospital

The pigment that gives red hair its distinctive fiery color may also put redheads at higher risk for the most deadly form of skin cancer, called melanoma, even if they shun the sun.

Researchers at Massachusetts General Hospital recently discovered that redheads with fair skin are at much higher risk for melanoma. This is true because the underlying mechanisms that give their hair its coloring also appear to strip them of some of their natural protection against the disease, says the study led by David E. Fisher, MD, PhD, which appeared in the November 15, 2012, issue of Nature.

The number of melanoma cases has been steadily rising by three percent each year, especially among fair-skinned people. This is particularly concerning because melanoma can grow and spread aggressively if it’s not caught early.

Researchers noticed that fair-skinned redheads sometimes developed melanoma on parts of their body that weren’t exposed to the sun, which led them to suspect that UV radiation may not be the only risk factor at work.

Mass General researchers confirmed this suspicion by running experiments on mice that were specially bred to have the redheaded traits they wanted to study. The results showed that, surprisingly, at least part of the increased melanoma risk for this red haired group remained even when sun exposure wasn’t a factor.

Instead they found, it’s the pigment inside the skin that turns hair red, which causes oxidative damage inside the skin. This underlying damage is what allowed melanomas to form.

THE ROLE OF PIGMENT PRODUCTION

Pigment production, which helps give hair its color, is controlled by something called the melanocortin 1 receptor (MC1R). It’s found inside melanocytes, which are the melanin-producing cells that become cancerous in people with melanoma.

In dark-haired animals, melanocyte-stimulating hormone binds with MC1R to produce a black/brown pigment, called eumelanin. Eumelanin not only gives the hair its dark color, but it also has a second function, shielding the skin’s DNA from UV waves. Redheads, on the other hand, have an inactivated MC1R variant. Their melanocytes produce a red/yellow pheomelanin pigment, which offers weak UV shielding, and they don’t produce that DNA-protecting eumelanin.

In his 2012 study, Dr. Fisher found that when he expressed the most common melanoma oncoprotein in redheaded mice, instead of developing benign moles, which would be the typical response, these mice developed invasive melanoma tumors, even when researchers didn’t expose them to UV radiation.

Mice with different skin and hair colors didn’t share this risk. Albino mice, for example, seemed to have additional protection against melanoma, despite their fair skin. The same was true for the dark haired mice whose eumelanin seemed to prevent this oxidative damage to the skin.

EXPLORING PREVENTIVE STRATEGIES

With this new information about elevated melanoma risk for redheads the question now becomes, how to reduce that risk.

Using antioxidants to counteract the DNA damage to the skin might be one way to reduce risk. But Dr. Fisher cautions that in some cases antioxidants may actually have the reverse effect, so researchers need to study it further.

Dr. Fisher and colleagues are also looking at other strategies, such as adding protective components to sunscreens, to counter the oxidative damage to the skin as well as those that darken the melanocytes to provide better protection against UV light.

While this work progresses, it’s important for people with red hair to continue to protect themselves from damaging UV rays by limiting sun exposure. Even though red heads may have a higher risk for melanoma even without the sun, exposure to UV radiation may drive that risk even higher, so it’s more important than ever to cover up.

One way to protect the skin is by using sunscreen, which cannot only prevent other forms of skin cancer, but protect against sunburns and premature aging.

Sources

1. Planta, Margaret B. “Sunscreen and Melanoma: Is Our Prevention Message Correct?” The Journal of the American Board of Family Medicine 24, no. 6 (November 1, 2011): 735–739.  2. Mitra, Devarati et al. “An Ultraviolet-Radiation-Independent Pathway to Melanoma Carcinogenesis in the Red Hair/Fair Skin Background.” Nature 491, no. 7424 (November 15, 2012): 449–453. 3. Cui, Rutao, Hans R. Widlund, Erez Feige et. al. “Central Role of P53 in the Suntan Response and Pathologic Hyperpigmentation. Cell, No. 5 (March 9, 2007): 853-864.