UV exposure may not increase melanoma risk in skin of color
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Melanoma development in skin of color may not be exacerbated by UV exposure, according to a study published in JAMA Dermatology.
“Melanoma incidence is much lower among people with skin of color; however, melanoma is often diagnosed at later stages with resulting lower survival rates,” Fabiana C. P. S. Lopes, MD, of the division of dermatology, department of internal medicine, Dell Medical School, The University of Texas at Austin, and colleagues wrote. “Numerous studies, including meta-analyses, have consistently demonstrated that increasing UV exposure is associated with higher rates of melanoma. However, much of the work demonstrating this association has been conducted exclusively in fair-skinned populations.”
The systematic review, using the PubMed, Cochrane and Web of Science databases, included peer-reviewed original studies that analyzed UV exposure as a risk factor for cutaneous melanoma in people with skin of color.
“People with skin of color constitute a wide range of racial and ethnic groups with varying melanin concentrations and varying susceptibility to UV-induced skin damage,” the authors wrote.
All races, ethnicities and tanning abilities except for non-Hispanic white individuals were included.
Thirteen studies met the criteria for inclusion, including seven ecological studies, five cohort studies and one case-control study.
Of the 13 studies, 11 showed no association between UV exposure and melanoma in skin of color. One showed a small positive relationship between UV exposure and cutaneous melanoma in Black male subjects, while one showed a weak association in Hispanic male subjects.
“Patients of color that develop melanoma may unnecessarily blame themselves for not wearing sunscreen, which has never shown to improve melanoma-related outcomes in people with skin of color,” Adewole S. Adamson, MD, MPP, corresponding study author, told Healio. “The way to reduce melanoma-associated disparities in people with skin of color should focus on education and improving access to high-quality health care, not UV protection.”
One caveat to this study, however, is that protection from UV exposure may have benefits for other disorders, including photoaging, melasma and post-inflammatory hyperpigmentation, according to Adamson.
“Our findings do not include people that may be at high risk, such as those with compromised immune systems,” he said.
Perspective
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Malignant melanoma (MM) is a clinically heterogeneous disease and is potentially the most deadly form of skin cancer. MM can be stratified into distinct biological subtypes when clinical, histologic, ethnicity, genetic susceptibility, molecular alterations and environmental ultraviolet radiation (UVR) exposure are considered.
Recently, molecular changes associated with melanoma biology and response to treatment are being used to define melanoma groups. The mitogen-activated protein kinase (MAPK) pathway is the most frequently mutated oncogenic pathway in 98% of cutaneous melanoma. Melanomas can be divided into heterogeneous molecular subtypes, BRAF, NRAS, NF1 and triple wild-type. BRAF mutations are the most prevalent and constitute more than 50% of cutaneous melanomas. NRAS mutations are mutually exclusive of the BRAF mutations and compose 15% of mutations in MM. Triple wild-type tumors have been overestimated, and NF1 gene mutations are more prevalent than previously thought. And secondary mutations in TP53 gene have also been described. None of these mutations had been associated with UVR exposure. The most common mutations in melanomas are in the telomerase reverse transcriptase (TERT) promoter. These mutations commonly bear a UVR footprint.
Both the complex epidemiological characteristics of UVR exposure and the diverse clinical presentation of MM have hampered the ability of clinicians and health policy makers to accurately advise on UVR safety. This is in contrast to keratinocyte-origin skin cancers that show UVR signature mutations or UVR footprint — cyclopyrimidine dimers (CPD) and pyrimidine-pyrimidone photoproducts — in more than 80% of lesions. It took decades of epidemiological and correlation studies to finally find the molecular answer. Apart from UVR damaging DNA directly, it also produces reactive oxygen species and UVR-induced superoxide and nitric acid, which lead to electron excitation within melanin fragments. These high energy levels of melanin derivatives transfer to DNA, creating mutagenic CPDs long after sun exposure. This landmark study raises the possibility that melanin may play a carcinogenic role.
When MMs are divided into those arising in chronically sun-exposed areas (head and neck) vs. those in internment exposed areas (trunk), mutations in NRAS, NF1, TP53 and BRAF without classic V600 mutations predominate in head and neck, and BRAFV600 predominates in truncal lesions. NF1 mutations are associated with desmoplastic melanomas, which have a strong association with UVR damage. UVR is known to contribute additional UVR signature mutations from the earliest onset of melanocytic proliferation (nevus) to premalignancy and early malignancy, and invasive-state UVR can also alter populations of adaptive immune cells in the skin-reducing immune response. UVB-induced keratinocyte and epidermal T cell apoptosis reduce the number of dendritic Langerhan cells as effective antigen-presenting cells lead to induction of systemic regulatory T cells (Treg) that suppress the immune response and inflammation.
In the recently published JAMA Dermatology article, the authors conducted a literature analysis to critically asses and synthesize the published data regarding the association of UVR and the risk of MM in skin of color. After their systematic review, the authors concluded that UVR may not be an important risk factor in melanoma development in people with skin of color. However, no molecular or immunological studies were included. In addition, the circumstantial evidence that Hispanics in California and Florida have had a higher incidence of MM during the past 2 decades, developing disease at a younger age and more advanced disease with poor prognosis, was not discussed.
In my opinion, before we start recommending that people with skin of color not use photoprotection, we have to examine all the correct data and be prepared for data still not available in order to give complete and accurate advice.
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