{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:49:30Z","timestamp":1791226170294,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T00:00:00Z","timestamp":1555286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["beva.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Equine Veterinary Journal"],"published-print":{"date-parts":[[2020,1]]},"abstract":"Summary<\/jats:title>\n \n Background<\/jats:title>\n \n Belgian horses are commonly affected with ocular squamous cell carcinoma (\n SCC<\/jats:styled-content>\n ), the most common cancer of the equine eye. A missense mutation in damage\u2010specific\n DNA<\/jats:styled-content>\n binding protein 2 (\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n c.1013\n C>T<\/jats:italic>\n , p.Thr338Met) has been established as a recessive genetic risk factor for ocular\n SCC<\/jats:styled-content>\n in the Haflinger breed. A sample of Belgian horses with unknown\n SCC<\/jats:styled-content>\n phenotype was shown to possess this variant at a similar frequency to the Haflinger breed. Retrospective studies indicate that chestnut coat colour may predispose to the development of\n SCC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To determine if\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n c.1013\n C<\/jats:italic>\n >\n T<\/jats:italic>\n is a risk factor for ocular\n SCC<\/jats:styled-content>\n in a strictly phenotyped sample of Belgian horses. To investigate associations between coat colour loci genotypes and ocular\n SCC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Study design<\/jats:title>\n Retrospective and prospective case identification, genetic investigation.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Genomic\n DNA<\/jats:styled-content>\n was isolated from blood, hair or formalin\u2010fixed paraffin\u2010embedded tissue from 25 Belgian horses with histologically confirmed ocular\n SCC<\/jats:styled-content>\n and 18 unaffected Belgian horses. Association testing of 34 single nucleotide variants from 11 genomic loci and genotyping for\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n c.1013\n C<\/jats:italic>\n >\n T<\/jats:italic>\n and coat colour alleles were performed. Exons of\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n were sequenced in four cases and two controls. Associations were analysed by Chi\u2010square or Fisher's exact tests and relative risk was calculated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Homozygosity for\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n c.1013\n C<\/jats:italic>\n >\n T<\/jats:italic>\n was significantly associated with ocular\n SCC<\/jats:styled-content>\n (P\n \u00a0<\/jats:italic>\n =\u00a07.4\u00a0\u00d7\u00a010\n \u22127<\/jats:sup>\n ). Seventy\u2010six per cent of affected horses were homozygous for the variant. Relative risk for homozygous horses developing\n SCC<\/jats:styled-content>\n was 4.0 (P\u00a0=\u00a01.0\u00a0\u00d7\u00a010\n \u22124<\/jats:sup>\n ). Sequencing\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n did not identify a variant more concordant with disease phenotype. An association between disease and coat colour loci was not identified.\n <\/jats:p>\n <\/jats:sec>\n \n Main limitations<\/jats:title>\n \n Phenotyping was determined at a single timepoint. Each included horse genotyped as chestnut, so association with this\n \n MC<\/jats:styled-content>\n 1R\n <\/jats:italic>\n variant could not be investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A missense variant,\n \n DDB<\/jats:styled-content>\n 2\n <\/jats:italic>\n c.1013C>T, p.Thr338Met, is a risk factor for ocular\n SCC<\/jats:styled-content>\n in Belgian horses. A genetic risk test is commercially available.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/evj.13116","type":"journal-article","created":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T09:49:54Z","timestamp":1553334594000},"page":"34-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A missense mutation in damage\u2010specific\n DNA<\/scp>\n binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8671-6661","authenticated-orcid":false,"given":"K. E.","family":"Knickelbein","sequence":"first","affiliation":[{"name":"Veterinary Medical Teaching Hospital University of California\u2010Davis Davis California USA"},{"name":"Veterinary Genetics Laboratory School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-4522","authenticated-orcid":false,"given":"M. E.","family":"Lassaline","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Singer\u2010Berk","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. B.","family":"Clode","sequence":"additional","affiliation":[{"name":"New England Equine Medical & Surgical Center PLLC Dover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. R.","family":"Famula","sequence":"additional","affiliation":[{"name":"Department of Animal Science University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. M.","family":"Michau","sequence":"additional","affiliation":[{"name":"Blue Pearl Specialty and Emergency Pet Hospital Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-7227","authenticated-orcid":false,"given":"R. R.","family":"Bellone","sequence":"additional","affiliation":[{"name":"Veterinary Medical Teaching Hospital University of California\u2010Davis Davis California USA"},{"name":"Department of Population Health and Reproduction School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2460\/javma.1976.168.01.61","article-title":"Squamous cell carcinoma in horses","volume":"168","author":"Strafuss A.C.","year":"1976","journal-title":"J. Am. Vet. Med. 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