Scientists have identified a genetic mutation that should help identify horses at risk for squamous cell carcinoma of the eye. A genetic DNA test is now available to help horse owners to make informed breeding decisions.
Squamous cell carcinoma (SCC) is a very common skin tumour, which is locally aggressive and can progress rapidly. It is the most common cancer found in equine eyes and the second most common tumour of the horse overall.
While it is more common in older horses of various breeds, Haflinger horses have a higher reported incidence of SCC, indicating that genetic factors play a role - at least in this breed. Thanks to a recent genetic study led by the University of California Davis, United States, horse owners can now identify horses at risk for ocular SCC and make informed breeding decisions.
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In a cover article in the International Journal of Cancer, scientists announced the discovery of a genetic mutation in horses that is hypothesised to impact the ability of damage-specific DNA binding protein 2 (DDB2) to carry out its standard role. Normally, the protein conducts DNA surveillance, looking for UV damage and then calling in other proteins to help repair the harm.
"The mutation is predicted to alter the shape of the protein so it can't recognise UV-damaged DNA," says Dr Rebecca Bellone, an equine geneticist at the Veterinary Genetics Laboratory and associate adjunct professor at UC Davis School of Veterinary Medicine. "We believe this is a risk factor because cells can't repair the damage and accumulate mutations in the DNA that lead to cancer."
Several equine breeds, including Haflingers, have a higher occurrence of limbal SCC, the form of the disease that originates in the junction between the cornea - the clear surface of the eyeball - and the conjunctiva that covers the white of the eye.
A former study, conducted by Bellone and one of her research partners, Dr Mary Lassaline, found that about 26 percent of SCC-affected horses in a retrospective study were Haflingers.
"The fact that we see this type of cancer in a relatively small breed with a narrow pedigree makes it a good model to study," says Dr Lassaline, associate professor of clinical equine ophthalmology at the UC Davis School of Veterinary Medicine.
Ocular SCC can lead to vision loss and even loss of the eye. In advanced cases, SCC can be locally invasive and spread to the orbit and eat away at the bone and eventually the brain - leading to loss of life. These recent study results offer a huge application in identifying horses at risk for developing SCC on two fronts.
"One, it's important for the individual horse with a known risk and we can be more vigilant about exams, as well as protecting their eyes from UV exposure," Dr Lassaline says. "If detected early, we can remove the tumour and save the eye. Secondly, that knowledge is important for making informed breeding decisions."
Scientists at the UC Davis Veterinary Genetics Laboratory were able to develop a genetic test for horses based on the research. The test determines if a horse carries the mutation or has two copies of the risk variant, putting it at highest risk for cancer.
Horses homozygous for the risk factor (R/R) are 5.5 times 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.
The UC Davis Veterinary Genetics Laboratory now offers a DNA-based test for the only known genetic risk factor for SCC in horses. Owners and breeders of Haflingers can use the DNA test result to identify horses at higher risk and to assist in breeding pair selection.
Homozygous horses (R/R) are advised to have routine eye exams performed by a veterinary ophthalmologist for early detection and a better prognosis, with the recommendation they should 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 in order to reduce the chances of producing horses that have a high risk of developing this cancer. The ideal mate, in either case, is a horse with no copies of the risk factor (N/N).
In addition to improving the health of horses, this study may have implications for human health as well. The gene found to be associated with equine SCC is also linked in humans to xeroderma pigmentosum complementation group E - a disease characterised by sun sensitivity and increased risk of cutaneous SCC and melanoma.
"There is an interesting parallel in humans with the mutation in this protein," Dr Bellone says. "Now we have the ability to understand why it's affecting the eyes of horses as well as the skin of humans."
The abstract of the article titled 'A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses' by Rebecca Bellone, Jiayin Liu, Jessica L. Petersen, Maura Mack, Moriel Singer-Berk, Cord Drogemuller, Julia Malvic, Barbara Wallner, Gottfried Brem, M. Cecilia Penedo and Mary Lassaline can be read here.