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Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.
Abstract: 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.
© 2018 Stichting International Foundation for Animal Genetics.
Publication Date: 2018-07-12 PubMed ID: 29999543DOI: 10.1111/age.12695Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research article presents a study on the genetic risk for squamous cell carcinoma, a form of eye cancer, in Haflinger horses occurring at different sites of the eyes (limbus and nictitating membrane), indicating similar hereditary susceptibility at both ocular locations due to a gene mutation.
Background of the research
- The study was undertaken due to the high incidence of squamous cell carcinoma (SCC), an eye cancer common in Haflinger horses.
- Earlier studies had identified a missense variant (mutation) in a particular gene (DDB2, p.Thr338Met) found on a specific chromosome (ECA12) as a risk factor for development of SCC in the limbus (part of the eye).
- Since SCC also occurs in another part of the eye, the nictitating membrane (third eyelid), the researchers felt the need to explore the role of this genetic variant in the development of SCC at this location as well.
Findings of the study
- The researchers discovered a common ancestor among Haflinger horses affected with either limbal SCC or nictitating membrane SCC. This supports the belief that there might be a recessive (requiring two genes for manifestation) risk factor causing cancer development at these two eye locations.
- Analysis of the genotype (genetic makeup) data from affected and unaffected horses showed that the same region on ECA12 associated with limbal SCC is also linked with nictitating membrane SCC.
- This finding was further confirmed by mining the specific locus (location on a chromosome) using a controlled set of cases and controls. The known risk variant, DDB2:c.1013C>T, p.Thr338Met, came out as a clear risk factor for nictitating membrane SCC, with 88% of the cases being homozygous (having two same genes) for this variant.
- No other polymorphism (variation in genetic sequence) was found to be more strongly associated with the cause.
Implication of the research
- The findings suggest that the genetic risk is equal for SCC development both at the limbus and nictitating membrane in Haflinger horses.
- Therefore, genetic testing of the DDB2 variant can be confidently applied for clinical management of this equine eye cancer and for guiding mating decisions aimed at reducing the probability of passing the condition to the next generations.
Cite This Article
APA
Singer-Berk M, Knickelbein KE, Vig S, Liu J, Bentley E, Nunnery C, Reilly C, Dwyer A, Dru00f6gemu00fcller C, Unger L, Gerber V, Lassaline M, Bellone RR.
(2018).
Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.
Anim Genet, 49(5), 457-460.
https://doi.org/10.1111/age.12695 Publication
Researcher Affiliations
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- 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.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- Department of Surgical Services, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA.
- School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
- Insight Veterinary Specialty Pathology, 6902A Bennett Ave., Austin, TX, 78752, USA.
- Genesee Valley Equine Clinic, LLC, Scottsville, NY, 14546, USA.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, Hochschulstrasse 6, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Hochschulstrasse 6, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Hochschulstrasse 6, Bern, Switzerland.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
- 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
- Animals
- Carcinoma, Squamous Cell / genetics
- Carcinoma, Squamous Cell / veterinary
- Chromosomes, Mammalian
- DNA-Binding Proteins / genetics
- Eye Neoplasms / genetics
- Eye Neoplasms / veterinary
- Horse Diseases / genetics
- Horses
- Limbus Corneae / pathology
- Microtubule-Associated Proteins / genetics
- Nictitating Membrane / pathology
- Polymorphism, Single Nucleotide
Grant Funding
- 16-06 / UC-Davis Center for Equine Health
- State of California Pari-Mutuel Fund
- Morris Animal Foundation
Citations
This article has been cited 6 times.- Miglinci L, Reicher P, Nell B, Koch M, Jindra C, Brandt S. Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma.. Pathogens 2023 Jan 23;12(2).
- Crausaz M, Launois T, Smith-Fleming K, McCoy AM, Knickelbein KE, Bellone RR. DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds.. Genes (Basel) 2020 Dec 5;11(12).
- Chen L, Bellone RR, Wang Y, Singer-Berk M, Sugasawa K, Ford JM, Artandi SE. A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma.. DNA Repair (Amst) 2021 Jan;97:103022.
- Levitt S, Osinchuk S, Sandmeyer L. Diagnostic Ophthalmology.. Can Vet J 2020 Jul;61(7):789-791.
- Singer-Berk MH, Knickelbein KE, Lounsberry ZT, Crausaz M, Vig S, Joshi N, Britton M, Settles ML, Reilly CM, Bentley E, Nunnery C, Dwyer A, Lassaline ME, Bellone RR. Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses.. Int J Genomics 2019;2019:3610965.
- Jeanes EC, Koll-Hampp S, Dawson C, Dunkel B, Tetas Pont R. Rhomboid blepharoplasty and cryotherapy for the treatment of a squamous cell carcinoma on the lower eyelid in a horse.. Clin Case Rep 2019 Jan;7(1):40-46.
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