MC1R minor variants and the multiple pathways to melanoma

Menée à partir de données internationales portant sur 233 jeunes patients et 932 patients adultes tous atteints de mélanome et sur 932 témoins, cette étude de cohorte rétrospective analyse l'association entre des variants du gène MC1R et le risque de développer la maladie pendant l'enfance et l'adolescence

Résumé en anglais

The gene for the melanocortin 1 receptor ( MC1R) is unusual. It is a single exon, and many mutations lead to a reliable change in whole organism pigmentation, affecting appearance and response to ultraviolet (UV) radiation. As a result, MC1R variation commonly arises as animals move into different environments and is often central to speciation. As humans migrated away from the tropics, there was a relaxation of selection against sunburn, along with a probably positive selection for efficient vitamin D production in lower UV radiation. MC1R in these Northern populations, in both Europe and Asia, acquired several independently arising mutations that partly or completely abrogate MC1R function, leading melanin production in melanocytes to switch from dark eumelanins to orange-brown pheomelanins. These gene variants are sufficiently frequent that the compound heterozygote state (ie, the individual carries a different mutation on each chromosome) is common, for example, in the British Isles, Germany, and Scandinavia. Carrying two variants of large effect can lead to red or light-coloured hair, pale skin, and freckling. Individuals with this phenotype have an increased risk of developing cutaneous melanomas, most noticeably as a consequence of moving (either temporarily, for holidays, or permanently) to high UV environments.