Red Alert: How red hair can cause skin cancer without sun exposure

I’m not usually that interested in research completely based on mouse studies, but any paper that starts with ‘People with pale skin, red hair, freckles and an inability to tan…‘ is always going to get my attention.

People like me, with the ‘red hair/fair skin’ phenotype, are pretty bad at dealing with the sun. Not only do we get sunburnt much more easily, but we have the highest risk of developing melanoma, the deadliest form of skin cancer. It is (hopefully) very well known that exposure to UV light increases the risk of melanoma. However, unlike other other skin cancers, melanoma also appears to develop independently of UV light, although this has been poorly studied to date.

The sun can be your worst enemy when you’re ginger. (Photo credit: coltera)

In a letter published in Nature this week, researchers wanted to see if hair-colour pigments affect this UV-independent pathway for melanoma. To do this, they engineered mice to mimic human complexions by mutating a gene known as MC1R. This is responsible for producing the pigment eumelanin which is dark coloured and results in dark hair. Most people with red hair have an inactive form of MC1R, which instead leads to the red-coloured pheomelanin being produced.

The researchers compared mice with black hair (active MC1R), red hair (inactivated MC1R) and albinism (produces neither pigment). In addition, all the mice had a specific mutation that causes benign moles, but leaves them predisposed to developing melanoma. The mice were kept away from sources of UV light and their health was charted over time.

The differences are startling. In under a year 50% of the red-haired mice had died compared to only 20% of the black-haired or albino mice. This, and further tests, seem to suggest that producing pheomelanin is actually harmful, increasing the rate of melanoma when there is no UV light.

Pheomelanin is responsible for the colour of red hair, but could also cause cancer

It was also apparent that the DNA of the red-haired mice had suffered twice as much oxidative damage as the albino mice. It is known that UV light causes oxidative DNA damage and that this increases the chances of mutations occurring. In previous studies looking at UV radiation, it was thought that eumelanin protects against this damage. However, the mice in this study show that pheomelanin is actually harmful and eumelanin has little effect under these conditions. It’s still not clear how this damage was created in the absence of UV light or why production of pheomelanin made it worse.

The authors of the paper make it very clear that UV radiation is still an important factor in the development of skin cancer, but suggest that this UV-independent pathway should be considered in the future for strategies to prevent melanoma, especially for gingers.

Redheads have long understood that we lack the natural sun protection that others enjoy, but it is still quite a shock to think that our distinctive colouring is actively causing us damage. However, this study was done under very artificial conditions, and the rates that the researchers saw are far higher than we can plainly observe. After all, we don’t see half of redheads dying every year. But whatever your hair colour, melanoma is still very deadly – one American dies from melanoma every hour. So make sure you don’t forget your sunscreen.