Redheads and fair skinned people are more susceptible to developing skin cancer, regardless of whether or not they expose their skin to the sun, researchers from Massachusetts General Hospital (MGH) reported in the journal Nature.

The authors explain that the kind of skin pigment that predominates in red-haired and fair-skinned people may be a contributing factor in melanoma risk.

Senior author, David Fisher, MD, PhD, 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.”

There are several types of pigment melanin in human skin:

  • 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 know that red/blond melanin is less effective than dark melanin in protecting against ultraviolet damage. However, the authors identified some “hints” that melanoma rates among fair-skinned and red-headed people cannot be fully explained by poorer UV (ultraviolet) protection.

They found that the melanoma risk occurs in areas of the skin that are not exposed to the sun’s rays.

Sunscreens do help reduce UV exposure and the damage. However, several studies have suggested that they may not be as good at protecting against melanoma as against other kinds of skin cancers.

In this study, the scientist used strains of mice with virtually identical genes, except for the gene that controls which type of melanin is produced. They had dark mice – with the typical variant leading to a predominance of dark melanin. The other mice were the “red hair-fair skin” version, with the same variant that makes people have red hair and fair skin.

They used a method created by team members from the University of California/San Francisco and Yale University to activate the melanoma-associated form of the BRAF oncogene in patches of the mice’s skin pigment cells. They expected that melanoma formation would only occur if they were exposed to UV radiation.

Surprisingly, they found that within a few months, half of the red animals developed melanomas, compared to very few of the dark ones.

The scientists checked to make sure that none of the mice had been exposed to UV radiation – they had not. They then wondered whether the red pigment itself might be causing the cancer.

They genetically disabled all the pigment production in the red hair/fair skinned mice, effectively creating a strain of “albino redheads”. The incidence of melanoma among these albino redheads dropped dramatically, indicating that there is something in the pigment itself that is encouraging the development of melanoma.

They wondered whether the generation of ROS (reactive oxygen species) might be involved in melanoma risk. ROS are unstable oxygen-containing molecules that harm cells. The scientists examined the skin of both the red and albino redhead mice.

They discovered high levels of a kind of DNA damage which 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 red-pigment-associated melanoma formation.”

The authors say that most likely antioxidant treatment would reduce this risk. However, Fisher emphasized that further studies are required to identify safe and effective ways of exploiting this knowledge.

Fisher said:

“Antioxidant treatments are not highly predictable in their actions and in some instances have even been seen to increase rather than prevent oxidative damage. Therefore we need to determine how to control this pathway safely and effectively. There are additional key questions to investigate, such as whether these findings also may pertain to people with, for example, fair skin and dark hair.

Right now we’re excited to have a new clue to help better understand this mystery behind melanoma, which we have always hoped could be a preventable disease. The risk for people with this skin type has not changed, but now we know that blocking UV radiation – which continues to be essential – may not be enough. It will be important for these individuals to be aware of changes in their skin and never hesitate to have something checked by a dermatologist, even if they have scrupulously protected themselves from sun exposure, which we continue to encourage. About six out of seven melanomas will be cured if they are found early, so we need to heighten awareness and caution.”

Written by Christian Nordqvist