The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma

Melanocyte stimulating hormone (MSH) plays an important role in determiningthe cutaneous response to ultraviolet radiation and may also influencemelanoma progression. We have previously shown that variants of themelanocortin receptor present on melanocytes, MC1R, are associated with sunsensitivity and red hair in a UK population and therefore now consider thegene as a candidate for melanoma susceptibility. We have compared thefrequency of known MC1R variants in the second and seventh transmembranedomains in 43 melanoma cases and 44 controls. MC1R variants were morecommon in cases than controls (chi 2 = 6.75, 1 d.f.; P = 0.0094) with arelative risk to carriers of variant alleles compared with normalhomozygotes of 3.91 (95% c.l.: 1.48-10.35), and a population riskattributable to carriers of 34.6% (95% c.i. 10.7-52.1%). The Asp84Gluvariant was only present in melanoma cases and appears to be of particularsignificance. The contribution of variant MC1R alleles was largelyindependent of skin type. Variants of the MC1R gene are likely to becausally associated with the development of melanoma.