The Skin Cancer Foundation Journal

MAY 2014

The 2012 edition of The Skin Cancer Foundation Journal features medically reviewed, reader-friendly articles such as tanning, the increasing incidence of skin cancer diagnoses among young women, & the prevalence of melanoma among white males over 50.

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S K I N C A N C E R F O U N D A T I O N J O U R N A L 76 International than people who had the much more common variations of MC1R linked to brown and black hair. MC1R is the most thoroughly studied mela- noma risk gene, and its main function is to de- termine the type and balance of pigment in the skin, hair, and eyes. Redheads predominantly have a type of melanin called "pheomelanin," associated with red/yellow pigments, while darker-haired, darker-skinned people mainly have a type of mel- anin called "eumelanin," associated with black/ brown pigments. People who carry the red hair variants of MC1R have signifcantly higher risks of melanoma than people who carry the black/ brown variants, so the discovery that they had less proliferation of their melanocytes after UVR ex- posure was a surprising twist. This raised the ques- tion as to what mechanism beyond pigment cell proliferation might be responsible for redheads' increased melanoma risk. The answer might come from a recent study at Massachusetts General Hospital in Boston. Us- ing mouse models, the research team compared melanoma incidence in mice with red, albino and dark coat colors. They found that the mice with red coat color had the high- est incidence of invasive melanomas, even higher than for the albinos (who are congenitally devoid of pigment alto- gether), even when they had no UV exposure. The researchers suggested that in the red-haired mice, the intrinsic prop- erties of their pheomelanin were triggering melanomas. 4 It is thought that pheomelanin undergoes oxidation upon exposure to solar ultraviolet radiation, producing free radi- cals, highly reactive toxic molecules that in turn damage the pigment cells' DNA. However, these mouse fndings suggest there is a second mechanism, apart from UVR exposure, that also increases redheads' melanoma risk. These animal fndings of course need to be confrmed in human studies, but they point to the complexities of melanoma preven- tion in redheads. Pigment produced naturally by melano- cytes is designed to protect the skin from the harmful ef- fects of sunlight, but for people who produce pheomelanin, this equation may be turned on its head: their pigment not only ofers weaker shielding ability against UV compared to eumelanin, but may actually exacerbate the damage caused by the sun. Speculating further, redheads' pheomelanin may increase their melanoma risk even if they have no UVR ex- posure, like an attack from within. Conclusions I n the past few years, we have come a long way in un- derstanding how melanoma arises at the cellular level. In 2009, scientists in Hinxton, UK, mapped the complete ge- netic material of a melanoma taken from a patient, identify- ing thousands of mutations caused by UV radiation. 5 This was the frst time UV damage could be seen throughout a melanoma's genetic material. The study, published in Nature, all but confrmed UV damage as a cause of the disease. Now, the new research underscores sunlight's efects on the key cells that give rise to melanoma, and provides new molecular evidence of sunscreen's usefulness in skin cancer prevention. No matter how careful someone is about sun- screen use, however, some UVR gets through to the skin, so remember that it is just one vital strategy in the arsenal of sun protection, along with shade, sun-protective clothing, wide-brimmed hats, and UV-blocking sunglasses. This is es- pecially true for redheads; with no ability to tan, and high susceptibility to rapid sunburning, they need every means at their disposal to stave of sun damage and skin cancer. In addition, since their pigment itself may promote carcino- genesis, redheads need to be especially vigilant in reduc- ing their sun exposure and acutely aware of any changes in their skin, which could herald the frst signs of cancer. With no ability to tan, and high susceptibility to rapid sunburning, redheads need every means at their disposal to stave off sun damage and skin cancer. Normally, skin pigment helps protect us from the sun . But redheads' skin pigment may exacerbate sun damage. References available on p. 97

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