THE ASP84GLU VARIANT OF THE MELANOCORTIN-1 RECEPTOR (MC1R) IS ASSOCIATED WITH MELANOMA

Melanocyte stimulating hormone (MSH) plays an important role in determ ining the cutaneous response to ultraviolet radiation and may also inf luence melanoma progression. We have previously shown that variants of the melanocortin receptor present on melanocytes, MC1R, are associate d with sun sensitivity and red hair in a UK population and therefore n ow consider the gene as a candidate for melanoma susceptibility We hav e compared the frequency of known MC1R variants in the second and seve nth transmembrane domains in 43 melanoma cases and 44 controls. MC1R v ariants were more common in cases than controls (chi(2) = 6.75, 1 d.f. ; P = 0.0094) with a relative risk to carriers of variant alleles comp ared with normal homozygotes of 3.91 (95% c.i.: 1.48-10.35), and a pop ulation 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 allel es was largely independent of skin type. Variants of the MC1R gene are likely to be causally associated with the development of melanoma.