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. SCCs frequently originate in the limbus (LSCC) and have the potential to invade the cornea and lead to visual impairment and destruction of the eye. The Haflinger breed appears to be overrepresented for LSCC, with a high prevalence estimated to be between 25-69%.  Despite this high occurrence, little is known about the etiopathogenesis of the disease.  In a retrospective study 18 affected Haflinger horses traced back to a single predominant sire, thus suggesting genetics plays a role in this disease.  To investigate the genetics of LSCC, horses from the retrospective study as well as newly examined or reported cases were analyzed.  Seven additional LSCC affected horses trace back to the same sire previously identified.    Preliminary pedigree analysis supports a recessive mode of inheritance.   SNPs in or near three functional candidate genes - Tumor protein 53 (p53), Cyclooxygenase-2 (COX2), and Retinoblastoma 1 (RB1) - were not associated with LSCC.  Here we employ a genome wide association study (GWAS) in 24 samples (13 cases 11 controls) to identify other candidate loci for further investigation.