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 (, ). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds.

中文翻译：

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DDB2 T338M作为马眼鳞状细胞癌的遗传危险因素的其他证据。

鳞状细胞癌（SCC）是马匹中最常见的眼周癌，也是马匹中第二常见的肿瘤。先前发现损害特异性DNA结合蛋白2（DDB2，c.1012 C > T，p.Thr338Met）的错义突变与哈弗林格和比利时马的眼SCC密切相关，解释了这两个品种中76％的病例。为了确定DDB2中相同的变体是否对阿拉伯，阿帕卢萨和Percheron品种的眼SCC风险有影响，并确定该变体是否对口腔或泌尿生殖道SCC的风险有影响，组织学确认的SCC病例已对DDB2进行了基因分型变异和关联进行了调查。在Appaloosa品种中发现了具有DDB2风险等位基因杂合的泌尿生殖道SCC的马，但未检测到DDB2变体与SCC发生在该品种中任何位置的显着关联。在阿拉伯人中未鉴定出风险等位基因，并且对于风险等位基因，Percherons没有纯合子。分析了来自六个Haflinger的高通量测序数据，以确定来自先前关联的ECA12上483 kb位点的其他变异是否比DDB2变异更符合SCC表型。优先评估了60个多态性，并且该基因座中没有其他变异比DDB2更好地解释了遗传风险 等位基因（， ）。这些数据进一步支持了DDB2变体，特别是在Haflinger和比利时品种中， DDB2变体增加了眼睛SCC的风险。