Skin Cancer Risk Among Red Heads is Higher Even Without Sun

While it is well known that redheads and fair skinned people need to be careful about their exposure to the sun due to their increased risk of skin cancer, it may come as a surprise to learn that they are still more susceptible to skin cancer even if they do not expose their skin to the sun.

The researchers explain that the kind of skin pigment that is predominant in red haired and fair skinned people could be a contributing factor in melanoma risk.

David Fisher, M.D., Ph.D., chief of the MGH Department of Dermatology, director of the CBRC, said:

"We've known for a long time that people with red hair and fair skin have the highest melanoma risk of any skin type. These new findings do not increase that risk but identify a new mechanism to help explain . This may provide an opportunity to develop better sunscreens and other measures that directly address this pigmentation-associated risk while continuing to protect against UV radiation, which remains our first line of defense against melanoma and other skin cancers."

In human skin, there are several different types of pigment melanin. Eumelanin (dark brown or black melanin) is predominant in people with dark hair or dark skin. Pheomelanin (lighter blond to red melanin) is predominant in people with red hair, freckles and fair skin. Dermatologists already know that the red/blond melanin is less effective than dark melanin in protecting against ultraviolet damage, but the authors were able to identify some "hints" that melanoma rates among redheaded and fair-skinned people can't be fully explained by poorer UV protection.

For the study, researchers used strains of mice with virtually identical genes, except for the gene that controls the type of melanin that is produced. They had dark mice and another kind that served as the red hair fair skin version. Both types of mice had the same variants that lead to a dominance in either dark melanin or light melanin.

Then they used a method to activate the melanoma-associated from of the BRAF oncogene in patches of the mice's skin pigment cells, and expected that melanoma formation would only occur if they were exposed to UV radiation. However, they found that within a few months, half of the red mice developed melanomas, compared to very few of the dark ones.

The researchers checked to make sure that none of the mice had been exposed to UV radiation, and they had not. This caused them to wonder if perhaps the red pigment itself could be causing the cancer. So, the scientists genetically disabled all the pigment production in the red mice, effectively creating a strain of "albino redheads". They found that the incidence of melanoma among the albino redheads dropped dramatically, which indicates that there is something in the pigment itself that encourages the development of melanoma.

It was then wondered if the generation of reactive oxygen species might be involved in melanoma risk. ROS are unstable oxygen-containing molecules that harm cells.

The scientists examined the skin of the red and albino redhead mice and found high levels of a kind of DNA damage that is usually produced by ROS in the skin of red mice, but not in the albino redheads. They explained that this finding "supports oxidative damage as the mechanism behind the red-pigment-associated melanoma formation."

The researchers believe that antioxidant treatment would reduce this risk.