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UC Davis identifies genetic risk factor for squamous cell carcinoma in horses

May 30, 2017

Test can help veterinarians monitor at-risk patients, assist owners with breeding decisions.

Halflinger horses are more likely than other breeds to develop ocular squamous cell carcinoma. Photo courtesy of UC Davis.Equine veterinarians are all too familiar with squamous cell carcinoma (SCC), the most common cancer of the equine eye and second-most-common tumor in horses overall. Now, thanks to a recent genetic study led by the University of California, Davis, owners can identify horses at risk for ocular SCC and make smart breeding decisions.

In the cover article for the International Journal of Cancer, scientists revealed the discovery of a genetic mutation in horses that is thought to affect 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, according to a release from UC Davis. 

A horse's eye affected by SCC. Photo courtesy of UC Davis.“The mutation is predicted to alter the shape of the protein so it can't recognize UV-damaged DNA,” says Rebecca Bellone, PhD, an equine geneticist at the Veterinary Genetics Laboratory and associate adjunct professor at UC Davis School of Veterinary Medicine, in the release. “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 and the conjunctiva, the release states. Mary Lassaline, DVM, PhD, DACVO, associate professor of clinical equine ophthalmology at the UC Davis School of Veterinary Medicine, assisted with the recently published research. “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,” she says.

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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 bone and eventually the brain, leading to death. These recent study results help identify horses at risk for developing SCC in two ways, according to the Davis release: 

“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,” Lassaline says. “If detected early, we can remove the tumor and save the eye. Secondly, that knowledge is important for making informed breeding decisions.”

Scientists at the UC Davis Veterinary Genetics Laboratory have developed 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.

The study may have implications for human health as well, the UC Davis release asserts. The gene associated with equine SCC is also linked in humans to xeroderma pigmentosum complementation group E, a disease characterized by sun sensitivity and increased risk of cutaneous SCC and melanoma.

“There is an interesting parallel in humans with mutation in this protein,” Bellone says. “Now we have the ability to understand why it's affecting the eyes of horses as well as the skin of humans.”

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