Does pheomelanin make a person more prone to skin cancer? Is sun addiction real? David E Fisher, MD, PhD, chief, dermatology service director of the melanoma program at Massachusetts General Hospital Cancer Center and director of the cutaneous biology research center at MGH in Boston, Massachusetts set the record straight on the evidence-based connection between sun exposure , sun-seeking, and photoprotection during a panel discussion at the 2022 American Academy Dermatology Association Annual Meeting in Boston, Massachusetts.1
Myth: Melanoma only occurs on sun-exposed skin.
Fact: Patients with red-blonde pigmentation are more prone to melanoma in sun-exposed as well as non-sun-exposed skin.two
Fisher and colleagues examined the mechanism behind this phenomenon and found red-blonde pigment, called pheomelanin, actually contributes to the formation of melanoma because it causes oxidative stress and damage in the cell where it is made, elevating risk. The melanoma risk is even higher after UV exposure, but it is still elevated in red hair, light skin background, even without UV.
Research using dark, albino, and red mice revealed these findings, but there are human studies that validate them, Fisher told Dermatology Times®. He said that skin without pigmentation is actually at less risk than red-blonde pigmented skin. Providers treating patients with this pigmentation type should help reduce risk by watching them carefully and strongly encouraging skin checks and sun protection, he said.
Fisher mentioned that in unpublished observations, he and his colleagues found an association between red pigmentation and Parkinson’s disease. “In the studies we have done we have found the drug used to treat Parkinson’s, L-Dopa (a precursor to dopamine), is an intermediate in the melanin synthesis pathway,” he said in an interview with Dermatology Times®.
Animal studies found feeding red-haired mice L-Dopa makes more of the red pigment, which increases the risk of melanoma,”
In another set of unpublished research, Fisher said that while prior studies have shown a well-established correlation between the number of pigmented nevi and melanoma (with the number increasing from dark to light, and with melanoma risk increasing with the number of nevi) this is not the case for the red hair/light skin background.
He said that while it is thought that people with red pheomelanin pigment have fewer nevi, it is not because they have fewer moles. Actually, it is because the nevi are not visible due to a lack of concentration of pigment, and this has been discovered in animal studies.
“In mice, we see they are not only present but more abundant,” Fisher said in the interview. “As we study this more it may help us to identify precursor lesions in this population that place people at a higher risk for developing melanoma,” Fisher said. “If there is no dark pigment in a melanoma, it has been shown to be diagnosed when it is thicker, which carries a higher risk for outcomes.”
Myth: Patients ignore advice to stay out of the sun simply because they enjoy being outside.
Fact: Patients aren’t necessarily disregarding advice; going out in the sun can actually be habit-forming.
Fisher described the process, where a byproduct in the synthesis of melanin called β-endorphin, is an opioid neuropeptide that can lead to a pathway of UV-seeking behavior – also known as sun addiction.3
“The behavioral inclination to be in the sun is a big problem, because despite all the information we have about the risk of UV radiation and its contribution to melanoma, people still seek out the sun despite knowing this information,” Fisher said in the interview .
He added that halting sun exposure can even result in withdrawal symptoms, which was demonstrated in mice.3 “You can feel miserable if you stop receiving that rush,” he said. “This is a molecular pathway in our genome, not bad behavior. We’re just doing what our bodies are telling us to do.” This knowledge may be helpful in educating patients to be more effective at combating sun-seeking behaviors.
Myth: Chemical sunscreen is enough to protect against melanoma.
Fact: Most people use chemical sunscreens designed for UVB rays to prevent sunburns, but Fisher said that UVA, which has a longer wavelength and does not as readily cause burns, may also damage DNA and contribute to melanoma.
Fisher said he and his colleagues have discovered a relationship between UVA radiation and melanoma.
“We were able to study this specifically in genetic models in mice, and strikingly found that UVA has a very strong melanoma promoting action specifically by interacting with pheomelanin and causing mutations,” he told Dermatology Times®. I have added that UVB-protecting chemical sunscreens may not be enough and that a physical blocker is needed to help prevent damage.
“Our existing sunscreens block UVB, but most do not adequately filter out UVA,” Fisher explained in the interview. “Chemical sunscreens, while helpful against UVB, block what I call nature’s alarm—the sunburn—and might make people believe they are well protected,” Fisher said. New priority should be given to adding good UVA protection in our sunscreens, and this must be balanced with the safety of the ingredients for use. This will be a balancing act for the FDA.” He added that while UVB SPF protection is extremely important, without UVA protection it may give people a dangerous sense of confidence, especially for fair-skinned people who should be advised to wear clothing and broad brimmed hats to protect against sun exposure, use mineral sunscreens , and practice sun safety.
David E. Fisher, MD, PhD has the following disclosures:
Abcam–O(IP); Cell Marque Corporation – O(IP); Convance, Inc. – O(IP); Dako – An Agilent Technologies Company – O(IP); Diagnostic BioSystems – O(IP); Elsevier Inc. – O(IP); Ipsen–C(Fees); Pierre Fabre – A(Fees); Santa Cruz Biotechnology, Inc-O(IP); Soltego – B(ST); Tasca-F(ST); Thermo Fisher Scientific Inc. – O(IP); UpToDate, Inc. – O(IP); Ventana Medical Systems, Inc – O(IP);
- Fisher DE. Where’s the evidence? A critical evaluation of common cosmetic recommendations: Pigmented Lesions: What’s the False? Presented at: 2022 American Academy Dermatology Association Annual Meeting; March 25, 2022; Boston, Mass.
- Mitra D, Luo X, Morgan A, et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature. 2012;491(7424):449-453. doi:10.1038/nature11624
- Fell GL, Robinson KC, Mao J, Woolf CJ, Fisher DE. Skin β-endorphin mediates addiction to UV light. Cell. 2014;157(7):1527-1534. doi:10.1016/j.cell.2014.04.032