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Genes2020; 11(12); doi: 10.3390/genes11121460

DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds.

Abstract: Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye. A missense variant within the gene damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) was previously identified as a causal recessive genetic risk factor for the development of ocular SCC within Haflingers, Belgian Draft horses, and Rocky Mountain Horses, but not in the Appaloosa or Arabian breeds. This study aimed to evaluate three cases of ocular SCC in additional breeds and determine if DNA testing for the DDB2 variant in warmblood horses and Connemara ponies is warranted. Histopathology confirmed ocular SCC in all three cases and DNA testing confirmed each horse was homozygous for the DDB2 risk factor. The DDB2 risk allele frequency was estimated to be 0.0043 for Holsteiners (N = 115), 0.014 for Belgian Warmbloods (N = 71), and 0.22 for Connemara Ponies (N = 86). Taken together these data support using DNA testing for DDB2 in Connemara Ponies to assist in mate selection and clinical management. Given the low observed allele frequencies in both the Holsteiner and Belgian Warmblood breeds and that the case under investigation was a warmblood cross-bred, evaluating additional SCC affected warmbloods is warranted to fully determine the importance of DDB2 genotyping as a risk factor in warmblood breeds.
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Publication Date: 2020-12-05 PubMed ID: 33291392PubMed Central: PMC7762027DOI: 10.3390/genes11121460Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines the genetic risk found in three additional horse breeds for developing equine eye cancer known as Squamous Cell Carcinoma (SCC), facilitated by a particular genetic variant known as DDB2. The study advises for the use of DNA testing for this risk variant in certain breeds to assist in making breeding choices and veterinary treatments.

Understanding the Genetic Risk

  • The research hones in on squamous cell carcinoma (SCC), the most common type of eye cancer affecting horses. The occurrence of SCC is attributed to a genetic variant in damage-specific DNA binding protein 2, denoted DDB2.
  • This genetic risk factor was previously established in specific horse breeds, such as Haflingers, Belgian Draft horses, and Rocky Mountain horses. However, it was not found in Appaloosa or Arabian horse breeds.

Aim and Methodology of the Study

  • The study’s goal was to investigate the presence of this SCC risk factor in three additional horse breeds and evaluate if testing for the DDB2 variant is advisable for warmblood horses and Connemara ponies.
  • The methodology comprised examining three cases of SCC in these breeds. For all these cases, ocular SCC was confirmed through histopathology, a microscopic examination of the eye tissues. DNA testing also confirmed each horse was homozygous for the DDB2 risk factor, meaning they received two copies of the DDB2 variant, one from each parent.

The Findings and Implications

  • The frequency of the DDB2 risk allele—the variation of the DDB2 gene suspected of increasing the chances for SCC—was estimated in three breeds. It was found to be relatively low in Holsteiners and Belgian Warmbloods but considerably high in Connemara Ponies.
  • The findings suggest using DNA testing for the DDB2 variant in Connemara Ponies to aid in making breeding decisions and vet care. The data also support the need for further research on more warmblood breeds, given the low observed risk allele frequencies in Holsteiners and Belgian Warmbloods.
  • This research could lead to more informed breeding decisions to avoid inheriting the risk allele, as well as improved clinical management in detecting and treating SCC in horse breeds.

Cite This Article

APA
Crausaz M, Launois T, Smith-Fleming K, McCoy AM, Knickelbein KE, Bellone RR. (2020). DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds. Genes (Basel), 11(12). https://doi.org/10.3390/genes11121460

Publication

Genes
ISSN: 2073-4425
NlmUniqueID: 101551097
Country: Switzerland
Language: English
Volume: 11
Issue: 12

Researcher Affiliations

Crausaz, Margo
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Launois, Thomas
  • Bailly Vétérinaires Clinique du Lys, 77190 Dammarie-les-Lys, France.
Smith-Fleming, Kathryn
  • Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61802, USA.
McCoy, Annette M
  • Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61802, USA.
Knickelbein, Kelly E
  • Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA 95616, USA.
Bellone, Rebecca R
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.

MeSH Terms

  • Alleles
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / veterinary
  • DNA-Binding Proteins / genetics
  • Eye Neoplasms / genetics
  • Eye Neoplasms / pathology
  • Eye Neoplasms / veterinary
  • Gene Frequency
  • Homozygote
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horses / genetics
  • Neoplasm Proteins / genetics
  • Risk Factors

Conflict of Interest Statement

R.R.B. is affiliated with the Veterinary Genetics Laboratory, a genetic testing laboratory offering genetic diagnostic testing in horses and other species.

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Citations

This article has been cited 3 times.
  1. Quatember H, Nell B, Richter B, Rigler D, Dolezal M, Sykora S, Wallner B. Studying the Impact of the DDB2 T338M Missense Mutation on the Development of Equine Squamous Cell Carcinoma and Sarcoid. Animals (Basel) 2025 Mar 22;15(7).
    doi: 10.3390/ani15070911pubmed: 40218305google scholar: lookup
  2. Chow L, Flaherty E, Pezzanite L, Williams M, Dow S, Wotman K. Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome. Vet Sci 2024 Apr 7;11(4).
    doi: 10.3390/vetsci11040167pubmed: 38668434google scholar: lookup
  3. Wotman KL, Chow L, Martabano B, Pezzanite LM, Dow S. Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia. Cancer Immunol Immunother 2023 May;72(5):1185-1198.
    doi: 10.1007/s00262-022-03321-2pubmed: 36367558google scholar: lookup
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