{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:19:25Z","timestamp":1788326365627,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["P01 CA163222"],"award-info":[{"award-number":["P01 CA163222"]}]},{"name":"NIH","award":["R01 AR072304"],"award-info":[{"award-number":["R01 AR072304"]}]},{"name":"NIH","award":["R01 AR043369"],"award-info":[{"award-number":["R01 AR043369"]}]},{"award":["P01 CA163222"],"award-info":[{"award-number":["P01 CA163222"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AR072304"],"award-info":[{"award-number":["R01 AR072304"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AR043369"],"award-info":[{"award-number":["R01 AR043369"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Defense Melanoma Academy","award":["W81XWH2220052"],"award-info":[{"award-number":["W81XWH2220052"]}]},{"name":"Wigglesworth Professorship in Dermatology"},{"name":"Water Cove Charitable Foundation"},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cutaneous melanoma is the most lethal skin cancer, and risk is strongly shaped by pigmentary phenotype. The red-hair color phenotype, marked by red hair, fair skin, freckling, and poor tanning, carries elevated melanoma risk driven largely by loss-of-function variants in the melanocortin 1 receptor gene (MC1R). This risk is not explained by reduced ultraviolet protection alone. Impaired MC1R signaling shifts melanogenesis from photoprotective eumelanin toward pheomelanin, a pigment associated with oxidative stress and partly ultraviolet-independent melanomagenesis. MC1R may also influence melanoma susceptibility through pigment-independent effects on DNA damage responses, repair signaling, and genomic stability. These mechanisms support investigation of MC1R genotype, visible phenotype, nevus burden, pigment chemistry, and imaging-derived lesion metrics as complementary tools for risk stratification. Diagnosis is also distinctive in this population. Amelanotic and hypomelanotic melanomas are associated with the red-hair color phenotype, and their low pigmentary contrast may delay recognition and contribute to diagnosis at a more advanced stage. This review integrates genetic, molecular, biomarker, diagnostic, and therapeutic literature specific to red-haired populations. We argue that elevated biological susceptibility and diagnostic difficulty compound one another, and we outline priorities for MC1R-informed surveillance, imaging adapted to pigment-poor disease, pharmacologic modulation of MC1R-related pathways, and prospective risk models integrating genotype, phenotype, nevus burden, pigment biology, and imaging.<\/jats:p>","DOI":"10.3390\/ijms27177765","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unique Features of Melanoma Risk and Diagnosis in Red-Haired Populations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3222-7516","authenticated-orcid":false,"given":"Kiran R.","family":"Ebrahimi","sequence":"first","affiliation":[{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10257","DOI":"10.1038\/s41598-023-37333-4","article-title":"Causes of Death among Patients with Cutaneous Melanoma: A US Population-Based Study","volume":"13","author":"Sadeq","year":"2023","journal-title":"Sci. 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