Singer-Berk M, Knickelbein K E, Vig S, Liu J, Bentley E, Nunnery C, Reilly C, Dwyer A, Drögemüller C, Unger L, Gerber V, Lassaline M, Bellone R R
Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA, 95616, USA.
Anim Genet. 2018 Oct;49(5):457-460. doi: 10.1111/age.12695. Epub 2018 Jul 12.
Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.
鳞状细胞癌（SCC）是影响马眼的最常见癌症，据记载在哈福林格马中发病率更高。最近，在12号常染色体上的基因损伤特异性DNA结合蛋白2（DDB2，p.Thr338Met）中的一个错义变体被确定为哈福林格马角膜缘SCC发生的一个风险因素。SCC也发生在瞬膜上；因此，有必要研究这个错义变体在瞬膜SCC中的作用。在这项研究中，在患有角膜缘SCC或瞬膜SCC的哈福林格马中鉴定出一个共同祖先，从而支持了在两个眼部位置发生癌症的隐性风险因素。对有和没有瞬膜SCC的哈福林格马的基因型数据进行分析发现，与角膜缘SCC相关的12号常染色体上的同一区域也与瞬膜SCC相关（P < 2.04 × 10）。使用25例病例和49例对照对该位点进行精细定位支持了以下假设，即DDB2:c.1013C>T，p.Thr338Met是瞬膜SCC的一个风险因素，因为我们88%的病例对该变体是纯合的，且没有其他多态性与之有更强的关联（P = 4.13 × 10）。这些数据表明，哈福林格马角膜缘和瞬膜SCC发生的遗传风险是相同的，并验证了对DDB2变体进行基因检测在临床管理和交配决策指导中的应用。
