People with red hair may be at greater melanoma risk than previously thought.
Red hair pigment production, not merely light skin and exposure to UV radiation, contributes to redheads' higher risk of skin cancer, according to a new study.
For over 20 years, researchers have attributed the higher risk of skin cancer for redheads to their typically fair skin, which is especially vulnerable to UV light.
But the study, published in BioEssays and performed by researchers at MGH/Harvard Cutaneous Biology Research Centre, offers two hypotheses on why red pigment might cause skin cells to be vulnerable to cancer.
Cells produce two types of pigment: dark brown eumelanin and red/orange pheomelanin.
First, pheomelanin production has been linked with oxidative stress, which can lead to DNA damage and ultimately cancer.
Second, researchers hypothesize that pheomelanin production could use up cells' antioxidant stores, increasing vulnerability to cancer.
In either case, the findings suggest that redheads should take additional precautions to prevent melanoma, even if they are already diligent about avoiding the sun and using high SPF sunscreen.
"Redheads should get more frequent body checks," said Jeanine Downie, a spokeswoman for the Skin Cancer Foundation. "If they have no family history of skin cancer, they should still be checked at least twice a year, rather than the annual check we recommend for everyone else. If they have a family history of skin cancer, they should be checked every three months."
To isolate the effect of hair pigment so that it could be compared with the effects of UV light on fair skin, researchers experimented using mice.
Researchers deactivated a receptor in the mice called MC1R, which is involved in the production of pigment. In redheaded humans, that signal is very weak.
The mice fur turned red, and the mice developed melanoma - without the presence of any UV light or environmental stressors.
The results suggest that the pheomelanin synthetic pathway itself is carcinogenic.
"It was possible to completely remove UV and there was still a major incidence of melanoma that was attributable to the red pigment," said David Fisher, chief of dermatology at Massachusetts General Hospital in Boston.
Pheomelanin synthesis may also increase damage to the skin because hydroxyl radicals, produced as a byproduct, can damage DNA bases.
However, the jury is still out on the exact cellular effects of pheomelanin synthesis. "On one hand, pheomelanin might generate reactive oxygen species that lead indirectly or directly to DNA damage," the study's authors said. "On the other hand, pheomelanin synthesis might consume cellular antioxidant stores and make the cell more vulnerable to other endogenous reactive oxygen species."
Researchers noted that the two hypotheses are not mutually exclusive, and may act in concert to produce the observed carcinogenic effects of pheomelanin.
UV radiation is still a serious threat to people with fair skin, and may exacerbate the vulnerability created by the production of red pighment, the authors warned.
"We think a new prevention opportunity exists if we can block the form of reactive oxygen damage that the red pigment is producing," Fisher said. "We are focusing on what the possibilities are, what the directions for new research are and how that could impact treatment."
To best prevent melanoma, redheads should avoid direct exposure to sunlight, use SPF and reapply every hour, and wear broad-brimmed hats.