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Sarcoid tumors linked to genetic susceptibility in horses

A new study shows genetic differences in immune function partly account for why some horses get sarcoid tumors while others do not

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A horse’s genetic makeup influences whether or not they develop sarcoid skin tumors, according to a new study by an international research group led by scientists at the Baker Institute for Animal Health at Cornell University’s College of Veterinary Medicine.

Sarcoid skin tumors are the most common form of cancer in horses, the college noted, but little is known about why the papillomavirus behind them strikes some horses and not others…Until now.

The study mirrors findings in humans, as some people have a genetic susceptibility to human papillomavirus, which can cause cervical and other cancers.

“Many therapies have been proposed as the ‘best’ treatment for sarcoids,” said Doug Antczak, VMD, Ph.D., the Dorothy Havemeyer McConville Professor of Equine Medicine, who led the study.

In some horses, tumors develop as small bumps under the skin or as scaly lesions that easily can be removed by a veterinarian, but in other horses the problem becomes much more serious. Surgery, cryotherapy, laser treatment, injecting the tumors with drugs to kill the cells, radiation treatment and immunotherapy have all been shown to cure these recalcitrant tumors, “but some tumors tend to recur no matter what treatment is used, and there is no universal consensus on a uniformly successful therapy,” Dr. Antczak said.

It’s been thought for years that bovine papillomavirus (BPV) is the most likely culprit behind sarcoid tumors, according to Antczak. Recent work from Europe suggests variants of the BPV have become adapted to horses and are probably the cause of most sarcoids.

Antczak’s team applied a genome-wide association study to compare the genetic makeup of horses with and without sarcoid tumors at more than 50,000 sites in the equine genome. They studied 82 sarcoid-bearing horses from the United States and United Kingdom and 272 carefully matched controls that did not have sarcoids. They found regions on chromosomes 20 and 22 that tended to be different in horses diagnosed with sarcoids, evidence that a horse’s genes determine, in part, how susceptible it is to sarcoids, according to the researchers.

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“This is an example of more complicated genetics — multigene susceptibility,” Antczak said. “More than one genetic region is associated with susceptibility to sarcoids, and they don’t completely determine whether or not a horse will develop the disease once it’s exposed to BPV.”

This genetic link implicates the immune system in sarcoid susceptibility, according to the researchers. The region of chromosome 20 associated with sarcoid development is within a portion of the genome responsible for immune function called the Major Histocompatibility Complex (MHC) class II region. The MHC type associated with sarcoid susceptibility is very rare among Standardbred horses, a fact that may explain why sarcoid is diagnosed so rarely in this breed, the researchers noted.

This complex mix of virus, host genes and tumor development may have relevance to a related human condition, according to the researchers. Tumors caused by human papillomaviruses account for more than 5 percent of cancer cases worldwide. In women with cervical cancer, an association with the MHC class II region has also been shown.

“That should make a light bulb go off,” Antczak said. “It suggests there’s a common mechanism in both species for susceptibility to tumor progression that may involve subversion of the host immune response. By studying this phenomenon in horses you can learn about human cancer and vice versa.”

The study, funded with a grant from the Morris Animal Foundation, was published in the International Journal of Cancer. In addition to Cornell, researchers came from the University of Glasgow, Iowa State University and the University of Florida.

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