Role Of Coat Color Genotypes In Risk and Severity Of Melanoma In Gray Quarter Horses

A correlation between the gray coat color and melanoma formation has long been recognized in horses and recently been linked to a duplication in the STX17 gene. In the presence of the STX17 duplication, a deletion in the ASIP gene in Lippizaner horses also increases melanoma risk by increasing MC1R pathway signaling. We hypothesized that melanoma susceptibility in gray Quarter Horses (QH) is lower than in other gray breeds due to decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. 335 gray QH with and without dermal melanomas were genotyped for STX17, ASIP and MC1R genes. Age, gender and external melanoma presence and grade were recorded. The effect of age and genotype on melanoma presence and severity was evaluated by univariate and multivariate regression analyses. Melanoma prevalence and grade in this QH cohort are lower than in other breeds. Age was significantly associated with melanoma prevalence and severity. No significant effect of MC1R genotype on melanoma prevalence or severity was identified. In contrast to prior reports, an effect of the ASIP genotype was not detected. Low STX17 homozygosity precluded evaluation of the gray allele effect. This decreased melanoma prevalence and severity in gray QH could be due to infrequent STX17 homozygosity, a mitigating effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the MC1R signaling pathway, or differences in genetic background between breeds.