Figure 1

An illustration of the MC1R pigmentation pathway and the loci implicated in melanoma risk. The binding of melanocortin-stimulating hormone (α-MSH) to its transmembrane receptor, Melanocortin-1-receptor (MC1R), results in stimulation of adenylate cyclase (AC) to produce cAMP. An antagonist to α-MSH, called Agouti protein (encoded by ASIP loci), inhibits this interaction. The release of cAMP in the cytoplasm activates the melanosomal enzymes, including tyrosinase (TYR) and tyrosinase-related protein-1 (TYRP-1), on the cell membrane of the melanosomes, resulting in a shift of pigment synthesis from pheomelanin to eumelanin. The variants of the genes encoding these proteins are listed. The corresponding odds ratio represents the risk of developing melanoma in patients carrying these variants.