Created at the VGL Ocular Squamous Cell Carcinoma (SCC) in Haflinger and Belgian Horses

Quick Summary

Ocular squamous cell carcinoma (SCC) is a condition characterized by tumors of the limbus (junction of the cornea and sclera) and/or third eyelid.

Phenotype: Ocular Squamous Cell Carcinoma (SCC) is a condition characterized by tumors of the limbus (junction of the cornea and sclera) and/or third eyelid. If left untreated they may spread into the surrounding eye tissue and cause vision loss.

Mode of Inheritance: Autosomal recessive with incomplete penetrance

Alleles: N = Normal or non-risk, R = Risk for SCC

Breeds appropriate for testing: Belgian, Haflinger, Rocky Mountain Horse

Explanation of Results:

  • Horses with N/N genotype do not carry this risk variant for SCC and cannot transmit this SCC risk variant to their offspring.
  • Horses with N/R genotype are not at elevated risk of developing SCC, but are carriers. They may transmit this SCC risk variant to 50% of their offspring. Matings between two carriers result in a 25% chance of producing a foal that will be at elevated risk of developing SCC.
  • Horses with R/R genotype are 4-5.6 times more likely to develop ocular SCC. They will transmit this SCC risk variant to all of their offspring.
Price

$40 one test per individual animal

Additional Details

Researchers at the Veterinary Genetics Laboratory and the University of California, 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 eyelid.

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 eyelid, 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.

Testing for this SCC risk variant can help owners and breeders of Haflingers and Belgians identify horses at higher risk and can 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 heterozygous (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).

Turnaround Time
2-6 business days
Type of Sample

Species

Type of Test

Results Reported As
Test Result Ocular Squamous Cell Carcinoma (SCC) Status
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

Lassaline, M., Cranford, T. L., Latimer, C. A., & Bellone, R. (2015) Limbal squamous cell carcinoma in Haflinger horses. Veterinary Ophthalmology, 18(5), 404-408. doi: 10.1111/vop.12229

Bellone, R. R., Liu, J., Petersen, J. L., Mack, M., Singer-Berk, M., Drögemüller, C., Malvick, J., Wallner, B., Brem, G., Penedo, M. C., & 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.International Journal of Cancer, 141(2), 342-353. doi: 10.1002/ijc.30744

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. (2018). Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses. Animal Genetics, 49(5), 457-460. doi: 10.1111/age.12695

Knickelbein, K. E., Lassaline, M. E., & Bellone, R. R. (2018). Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and investigation of genetic contribution. Veterinary Ophthalmology, 22(2), 1–5. doi: 10.1111/vop.12612

Knickelbein, K. E., Lassaline, M. E., Singer‐Berk, M., Reilly, C. M., Clode, A. B., Famula, T. R., Michau T.M., & Bellone, R. R. (2019). A missense mutation in damage‐specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses. Equine Veterinary Journal. doi: 10.1111/evj.13116

Singer-Berk, M., Knickelbein, K.E., Lounsberry, Z.T., Crausaz, M., Vig, S., Joshi, N., Britton, M., Settles, M.L., Reilly, C.N., Bentley, E., Nunnery, C., Dwyer, A., Lassaline, M.E. & Bellone, R.R. (2019). Additional Evidence for DDB2 T338M as a genetic risk factor for ocular squamous cell carcinoma in horses. International Journal of Genomics, Vol. 2019, Article ID 3610965, 10 pages. doi: 10.1155/2019/3610965