Abstract

Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC cases were genotyped for the DDB2 variant and associations were investigated. Horses with urogenital SCC that were heterozygous for the DDB2 risk allele were identified in the Appaloosa breed, but a significant association between the DDB2 variant and SCC occurring at any location in this breed was not detected. The risk allele was not identified in Arabians, and no Percherons were homozygous for the risk allele. High-throughput sequencing data from six Haflingers were analyzed to ascertain if any other variant from the previously associated 483 kb locus on ECA12 was more concordant with the SCC phenotype than the DDB2 variant. Sixty polymorphisms were prioritized for evaluation, and no other variant from this locus explained the genetic risk better than the DDB2 allele (P = 3.39 × 10−17, n = 118). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds.

Highlights

  • Ocular squamous cell carcinoma (SCC) is the second most common tumor to affect the equine eye and in severe cases can lead to loss of vision or loss of life

  • A total of 120 Haflingers and 43 Belgians, including those horses used in previous studies (Table S1) [2, 3], were used to determine if sex and age were contributors to risk for ocular Squamous cell carcinoma (SCC)

  • Haflinger and Belgian horses affected with ocular SCC and homozygous for the DDB2 c

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Summary

Introduction

Ocular squamous cell carcinoma (SCC) is the second most common tumor to affect the equine eye and in severe cases can lead to loss of vision or loss of life. Previous research investigating the genetic risk for ocular SCC in the Haflinger breed identified a recessive mode of inheritance and a 483 kb locus on equine chromosome 12 11767256) that was associated with limbal and nictitating membrane SCC in the Haflinger breed [1,2,3]. This variant was strongly associated, but not perfectly concordant, with limbal and third eyelid SCC status in both the Haflinger and Belgian breeds, explaining 76% of the Haflinger and Belgian cases investigated [2,3,4]. A recent case report implicated this DDB2 variant as a potential risk factor for ocular SCC in Rocky Mountain Horses [5]. The first aim of this study was to gain further insight into ocular SCC development in Haflinger and Belgian breeds by investigating other risk factors, including age

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