In this issue of The Melanoma Letter, Dr. Fisher and his coauthor, Dr. Elisabeth Roider, reveal that along with high levels of pheomelanin, the “redheaded” MC1R polymorphisms are associated with decreased levels of glutathione, a major antioxidant. This reduced glutathione in turn predisposes cells to oxidative stress. Logic would suggest that diligent use of sunscreens and exogenous antioxidants might counteract the damaging effects of low glutathione and high eumelanin levels. However, paradoxically, in people with the mutant MC1R variant, these products may in fact contribute to further damage. Exogenous antioxidants increase cysteine levels, which may tilt melanin production away from protective eumelanin towards the less protective, inherently damaging pheomelanin. And sunscreens, by allowing unaware vulnerable individuals to stay in the sun longer without burning, may lead to mounting oxidative stress, inadequately counteracted by these individuals’ low glutathione levels. Thus, especially for those with the redheaded MC1R variant, clothing and shade may need to be the primary forms of sun protection, with sunscreen serving a secondary protective role. At the same time, people of all skin phenotypes and colors must be apprised that skin can be UV-damaged even without sunburn, and that sunscreens are best used as necessary, complementary protection, but never as an excuse to stay out longer.
As these new insights are refined and reinforced, and as the mechanisms involved in melanomagenesis are better elucidated, skin cancer prevention strategies will be increasingly tailor-made for individuals of different phenotypes and genotypes.