The melanocyte stimulating hormone receptor polymorphism: association of the V92M and A294H alleles with basal cell carcinoma.

Allelic variants in the melanocyte stimulating hormone receptor (MC1R) gene are susceptibility/outcome candidates for cutaneous basal cell carcinoma (BCC). We identified the val92met (V92M) and asp294his (A294H) alleles in 311 cases and 190 controls. The cases included four homo- and 53 heterozygotes for V92M and 12 heterozygotes for A294H and two compound heterozygotes (V92M/A294H). Allele frequencies were similar in controls. In the cases, we found no association between the alleles and skin type though A294H was more common in those with red hair (4/19) than with other hair colours (6/163) (P = 0.012). V92M was not associated with BCC numbers. Cases with A294H had fewer BCC in comparison with those without the allele though the difference was not significant. After inclusion of red hair in the model, A294H was significantly associated with fewer tumours. While MCIR alleles are attractive candidates for BCC, the variants studied did not influence susceptibility. The association with outcome was relatively weak. The large number of MC1R alleles and their low frequency, make assessment of the importance of this gene in the pathogenesis of skin cancers difficult.