Genetic Investigation of Limbal Squamous Cell Carcinoma in Haflinger Horses

Squamous cell carcinoma (SCC) is the most common cancer of the equine eye and the second most common tumor of the horse overall. SCC frequently originates in the limbus (LSCC) and has the potential to invade the cornea, leading to visual impairment and destruction of the eye. The Haflinger breed appears to be overrepresented for LSCC and these horses are diagnosed at a younger age. Despite the high occurrence, LSCC etiopathogenesis is not completely understood. Pedigree analysis of 34 LSCC affected horses traces all affected individuals back to a single prominent sire and supports a simple recessive mode of inheritance. To investigate this further, we performed a genome wide association study using 13 cases and 11 controls. With this relatively small sample set, two loci for further investigation were identified. Three SNPs on ECA 4 were the most significantly associated (P = 5.79 X 10^-5). Unfortunately upon further examination (11 additional cases and 12 controls) this locus was negated (P = 0.47). Additionally, four SNPs spanning a 1 Mb interval on ECA12, were also associated (P= 5.80 x 10^-04). Testing two of these SNPs in our replication study set confirmed this association (P = 3.79 X 10^-06), thus warranting further investigation of this region containing eight functional candidate genes. Genotyping both additional samples and SNPs on ECA 12 will be performed to confirm and refine the region of association. We aim to identify a causative DNA variant to aid in earlier detection and thus a better prognosis for affected horses.