Red hair
The pigment that causes hair to be red may cause cancer (wiki commons)

The pigment that causes hair to be red could be the reason why redheads are more at risk of skin cancer, researchers have said.

For over two decades, scientists have known that redheads are at increased risk of melanoma, but have always attributed this to their having pale skin.

However, a study published in Bioessays by researchers at the MGH/Harvard Cutaneous Biology Research Centre suggests this is not the case.

They have put forward two theories as to why the pigment in red hair itself is carcinogenic, independent of UV radiation to fair skin.

Skin cells produce two types of pigment - dark brown eumelanin and red/orange pheomelanin.

The latter, researchers found, is linked with increased oxidative stress in the skin, which in turn potentially causes DNA damage, leading to cancer.

The team also suggest that pheomelanin synthesis could use up cells' antioxidant stores, meaning cells are more vulnerable to cancer.

Researchers gave mice a common driver in the mutation of melanoma and then deactivated a receptor called MC1R, which is involved in the production of pigment - in redheads the signal it emits is very weak.

Lab mouse
The mice fur became red after researchers inactivated MC1R (wiki commons)

After deactivating MC1R, the mice's fur turned red and they developed melanoma, despite there being no environmental stressor such as UV light. This suggests the pheomelanin synthetic pathway is carcinogenic.

The team also found that pheomelanin production is associated with increased damage to the mouse skin, as it contained more hydroxyl radical damaged DNA bases. Hydroxyl radical can damage all types of macromolecules making it very dangerous to organisms.  

After finding the association, the researchers put forward two theories for the pathway between pheomelanin and oxidative DNA damage that leads to melanoma.

"On one hand, pheomelanin might generate reactive oxygen species [by-products of normal metabolism of oxygen that increase dramatically during times of environmental stress and result in damage to cells] that lead indirectly or directly to DNA damage," the study authors said.

"On the other hand, pheomelanin synthesis might consume cellular antioxidant stores [which help to prevent ROS] and make the cell more vulnerable to other endogenous ROS."

Concluding, the authors said: "It should be noted that these hypotheses are not mutually exclusive and may act in concert to produce the observed carcinogenic effects of pheomelanin.

"It should also be noted that the first hypothesis assumes that pheomelanin is able to generate ROS. While this has been proven in response to UVA irradiation, the absolute energy input requirements for ROS generation have not been determined."