UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Ocular Squamous Cell Carcinoma (SCC) in Haflinger and Belgian Horses

Introduction

Researchers at the Veterinary Genetics Laboratory and UC Davis School of Veterinary Medicine investigated ocular Squamous Cell Carcinoma (SCC) in the Haflinger and Belgian breeds and determined that a recessive mode of inheritance explains some of the genetic components involved in the development of this cancer. They also discovered a DNA marker that identifies horses at higher risk for this cancer occurring on the limbus (junction of the cornea and the sclera) and/or third eye lid.

Squamous cell carcinoma (SCC) is the second most common type of tumor in the horse and the most frequent tumor of the horse’s eye. Factors thought to increase risk for SCC include UV exposure, pigmentation, and genetics. Among reported cases, Haflingers and Belgians have higher incidence of SCC of both the limbus and the third eye lid, which suggests that genetic factors play a role in these breeds. When originating at the limbus, SCC can spread into the cornea, and quickly lead to visual impairment and destruction of the eye.

Our research identified a variant in the UV damage DNA repair gene, Damage-specific DNA Binding Protein 2 (DDB2) that was strongly associated with cancer risk in both the Haflinger and Belgian breed. Horses homozygous (R/R) for the risk variant factor are 5.6 times (Haflinger) or 4.0 times (Belgians) more likely to develop ocular SCC than those with one copy (R/N) or no copies (N/N) of the risk factor. This risk factor does not explain all cases of ocular SCC but it appears to be a major contributor in Haflingers and Belgians. Most recently, our research team identified a Rocky Mountain Horse with limbal SCC that was also homozygous for this risk variant. Therefore, this DNA test may also be appropriate for Rocky Mountain Horses.  

The VGL offers a DNA test for the only known genetic risk factor for ocular SCC in horses. Owners and breeders of Haflingers and Belgians can use the DNA test result to identify horses at higher risk and to assist in mating pair selection. Homozygous horses (R/R) are advised to have routine eye exams performed by a veterinary ophthalmologist for early detection and better prognosis, and to wear a UV protecting fly mask when out during the daylight hours. Breeding homozygotes (R/R) and heterozygotes (R/N) among or to each other should be avoided to reduce the chances of producing horses that have a high risk of developing this cancer. The ideal mate in either case (R/R or R/N) is a horse with no copies of the risk factor (N/N).

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Results reported as:

N/N No copies of the SCC-associated marker. Horse has a lower risk of developing limbal or third eye lid SCC.
N/R 1 copy of the SCC-associated marker. Horse has a lower risk of developing ocular SCC but can pass on the risk factor to 50% of the offspring.
R/R 2 copies of the SCC-associated risk marker. Horse is 4.0 (Belgian) or 5.6 (Haflinger) times more likely to develop SCC in its lifetime when compared to N/R and N/N. Routine ophthalmological exams and use of UV-protecting fly masks during sun exposure are advised.

References:

Bellone RR, Liu J, Petersen JL, Mack M, Singer-Berk M, Drögemüller C, Malvick J, Wallner B, Brem G, Penedo MC, & Lassaline M. (2017) A Missense Mutation in Damage-specific DNA Binding Protein 2 Is a Genetic Risk Factor for Limbal Squamous Cell Carcinoma in Horses. Int. J. Cancer  141(2):342-353.

  Knickelbein KE, Lassaline ME, Bellone RR. Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and investigation of genetic contribution. Vet Ophthalmol. 2018;00:1–5. https://doi.org/10.1111/vop.12612

Lassaline M, Cranford TL, Latimer, CA, & Bellone R. (2015) Limbal squamous cell carcinoma in Haflinger horses. Vet Ophthalmol 18(5) 404-408.

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. and Bellone, R. R. (2018), Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses. Anim Genet, 49: 457-460. doi:10.1111/age.12695

 

 
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