Un fattore inaspettato favorisce il melanoma nelle persone con capelli rossi e cute chiara

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In un articolo pubblicato online su nature medici del Massachusetts General Hospital, Cutaneous Biology Research Center e Cancer Center  hanno studiato dei topi geneticamente uguali che presentava due geni distinti per il colore scuro della pelle e per il colore rosso  e hanno attivato un oncogene BRAF in grado di favorire il melanoma. Dopo alcuni mesi metà dei topi con cute chiara hanno sviluppato un  melanoma rispetto a pochi melanomi nei topi con cute scura. Da ciò i deduce che potrebbe esserci un altro fattore che favorisce lo sviluppo di melanoma nelle persone rutiliche rispetto alla già conosciuta fotosensibilità

Leggi l’articolo: An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin backgroundPeople with pale skin, red hair, freckles and an inability to tan|[mdash]|the |[lsquo]|red hair/fair skin|[rsquo]| phenotype|[mdash]|are at highest risk of developing melanoma, compared to all other pigmentation types1. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin2. Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species345. Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers6. Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role17. Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAFV600E, into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1re/ebackground. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1re/e mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino-Mc1re/e mouse skin. These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage. Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention.

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