Why do redheads get melanoma more frequently?

As summer draws to a close in the Northern hemisphere, people with fair skin can breathe a sigh of relief. The days of sheltering from the sun to avoid sunburn and skin cancer are over. However, sunlight isn't the only risk factor.

Our editorial office is a stone's throw away from the beach in Brighton, on the South coast of the United Kingdom. And while the U.K. is not especially known for its sunny climate, those with fair skin up and down the country can be seen covering up when the sun does make a star appearance.

One such person is our Managing Editor Marie Ellis. While not a redhead, she is fair of skin with blonde hair. She doesn't tan, burns easily, and always covers up. Marie carries the same type of mutation that leaves redheads unable to make dark pigment, and this puts her at higher risk of developing melanoma.

This led us to wonder why the melanoma risk is so much higher for Marie and other pale-skinned people.

Pigment and sunlight

Too much sunlight is bad for the skin. The pigment in our skin that protects us from sunlight is called melanin. More specifically, melanin shields our DNA from harmful ultraviolet (UV) rays.

Humans have two different types of melanin. Eumelanin is brown-black, while pheomelanin is red-orange.

When we are exposed to sunlight, the melanocortin-1 receptor (MC1R) tells our pigment-producing melanocyte cells to make melanin. In the majority of the world's population, this leads to skin turning darker to avoid DNA damage.

But 1 to 2 percent of people have red hair, fair skin, and freckles and do not tan.

They carry a mutation in the MC1R receptor gene, which stops it from working properly. The cells only produce pheomelanin, which is not effective at shielding DNA from the damage that UV rays cause.

Turning the defective MC1R receptor back on

Last week, Medical News Today reported on a new study that showed that a chemical modification called palmitoylation is involved in turning the MC1R receptor on in response to sunlight.

But the palmitoyl tag cannot be added to the mutant version of the MC1R receptor that redheads carry. As a result, the receptor cannot do its job.

In a breakthrough discovery, the team found a way around this problem. They used a chemical that increases palmitoylation in a mouse model with the MC1R mutation.

When the mice were exposed to high levels of UV light, they had significantly lower melanoma rates. But unfortunately, sunlight is not the only risk factor.

Melanoma in non-exposed areas

Melanomas can occur anywhere on the body, not just in areas that receive the most sun exposure. Something other than UV light must be to blame in such cases.

A study published in Nature in 2012 found that in the absence of UV light, oxidative damage in melanoma tumors is very high.

The researchers blame pheomelanin for this. Something in the way that it, but not eumelanin, is produced must be promoting this damage.

These results were supported by a study published in the journal Nature Communications in 2016. The team found that those who carry the faulty MC1R gene have cancer-causing mutations that are not due to sunlight.

Importantly, this includes redheads (who carry two copies of this gene) as well as those who carry only one copy and are probably not aware of it, as they do not have red hair or fair skin.

Research has shown us that those with fair skin are at higher risk because they cannot shield themselves from DNA damage and because their pheomelanin promotes cell damage. But those who carry just one copy of a mutant MC1R gene are also at risk, indicating that there are probably other, as yet undiscovered, factors at play.

When the sunshine returns to our shores next summer, Marie will once again be avoiding the sun - the only thing proven to reduce melanoma risk in those with fair skin. But she can rest assured that scientists will continue their quest to unpick the mysteries that put her and many others at increased risk of melanoma.