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Melanocy stimulating hormone (MSH) plays an important role in determining the cutaneous response to ultraviolet radiation and may also influence melanoma progression. We have previously shown that variants of the melanocortin receptor present on melanocytes,  MC1R , are associated with sun sensitivity and red hair in a UK population and therefore now consider the gene as a candidate for melanoma susceptibility. We have compared the frequency of known  MC1R  variants in the second and seventh transmembrane domains in 43 melanoma cases and 44 controls.  MC1R  variants were more common in cases than controls χ 2  = 6.75, 1 d.f.;  P  = 0.0094) with a relative risk to carriers of variant alleles compared with normal homozygotes of 3.91 (95% c.i.: 1.48–10.35), and a population risk attributable to carriers of 34.6% (95% c.i. 10.7–52.1%). The Asp84Glu variant was only present in melanoma cases and appears to be of particular significance. The contribution of variant  MC1R  alleles was largely independent of skin type. Variants of the  MC1R  gene are likely to be causally associated with the development of melanoma.

The Asp84Glu Variant of the Melanocortin 1 Receptor ( MC1R ) is Associated with Melanoma