What Golden Retrievers Teach Us About Cancer

In September, Sara Fritz lost her six-year-old golden retriever, Emma, ​​to a particularly aggressive cancer called hemangiosarcoma. As a pet mom, she was heartbroken. As a practicing veterinary oncologist, she was frustrated.

More than 60 percent of golden retrievers will develop cancer in their lifetime, compared to about 25 percent of other breeds.

“All dogs can develop cancer, but Goldens have the highest probability,” Fritz said. “We think they have many genetic variants linked to cancer. We just didn’t target them and so we couldn’t target them.

However, this could change. Scientists are studying this popular breed, both to help dogs and to learn more about human cancers. Dogs and humans share most of the same genes.

The Morris Animal Foundation has had an ongoing study of golden retrievers for more than a decade, trying to identify the genetic, environmental, nutritional and other factors that influence cancer. And scientists at the University of California, Davis, looking to understand why some golden retrievers live longer than others, have discovered a genetic variant associated with increased longevity.

They found that golden retrievers with the variant had a lifespan nearly two years longer than those without it, a significant time difference for a dog. It is interesting to note that the mutation they identified came from a family of genes linked to cancers, particularly human.

The UC Davis researchers took an unusual approach, in that “we didn’t look for genes associated with cancer,” said Robert Rebhun, professor of surgical and radiologic services in the University School of Veterinary Medicine. UC Davis and co-corresponding author.

“We looked based on their lifespan,” Rebhun said. “What’s amazing is that looking at how long they lived, the genetic variant that appeared is a gene known to be associated with cancer.”

Good dogs and bad variations

More than 300 golden retrievers participated in the study, including Rebhun’s own dog Jessica. Scientists compared DNA from blood samples from golden retrievers living at 14 years old to those who died before the age of 12. They found that dogs carrying the genetic variant survived longer, on average up to 13.5 years compared to 11.6 years.

Rebhun said the gene appears to have a “good variant” and a “bad variant,” meaning one that favors survival, the other linked to shorter lives. “Jessie” developed a slow-growing soft tissue sarcoma at age 14, but lived to be 16 1/2, he said.

“She had one of the good variants and one of the bad ones,” he said. “Our theory is that the wrong one could contribute to the development of cancer, while the right one would have prevented it until the age of 14.”

The study also revealed intriguing differences between male and female dogs, raising the possibility that female hormones, such as estrogen, may be involved, he said.

Female dogs with a copy of the bad variant lived significantly shorter than female dogs who did not have the bad variant. In contrast, there was no difference between male dogs having a copy of the bad variant and male dogs not having it at all.

For both male and female dogs, having two copies of the wrong variant resulted in a significantly shorter lifespan.

The research “presents compelling evidence that this variant is linked to longevity in golden retrievers,” said Noah Snyder-Mackler, an associate professor at Arizona State University’s school of life sciences, who did not participated in the study.

“The results are tantalizing and, like most things in science, they raise more questions than they answer,” he said.

A family of cancer genes in dogs and humans

The specific variants identified in the study were found on a gene called ErbB4, also known as HER4. It is the canine equivalent of a gene present in a family of human genes whose variants are linked to cancer.

In the dog study, the ErbB4 gene variant was linked to an increase in lifespan equivalent to 12 to 14 additional years in humans, said geneticist Danika Bannasch, professor of population health and reproduction at UC Davis and co-corresponding author.

This study targets “one of the greatest mysteries of life, not only in dog science but also in human health,” said Elinor Karlsson, director of vertebrate genomics at the Broad Institute of MIT and Harvard, who also did not participate in the research.

“Why do some people live longer than others? Why do some dogs live longer than others? she says. “We don’t know why, but this study begins to address that question.”

ErbB4 variants appear to act in two ways. It can act as an oncogene – the cause of cancer – or behave as a tumor suppressor gene, which slows down disease. Rebhun said it’s not clear what triggers each behavior. “We don’t have an exact mechanism to say whether this variant stimulates cancer growth in golden retrievers or prohibits it, or how it does each,” he said.

The potential results could be significant. Previous research on a variant of the HER2 gene, which is in the same family as ErbB4, led to a significant advance in the treatment of human breast cancer, resulting in a targeted therapy called Herceptin for patients with HER2 positive breast cancer.

Hope for golden retrievers and their humans

Although experts say practical applications of the study are likely years away, they hope the results will lead to a test or other diagnostic tool to identify or treat vulnerable dogs — and perhaps even humans.

“Dogs and humans share many of the same environmental factors and genes, and they function similarly in both species,” Rebhun said.

He and his colleagues hope to conduct a larger study on golden retrievers and examine other breeds as well.

“Maybe we’ll find something else that increases longevity in other breeds,” he said. “We also want to study this variant in other breeds that don’t die from cancer as much as Goldens.”

Dogs’ cancer risk has done little to diminish their appeal. “They are simply wonderful dogs, which makes their high cancer rates particularly tragic,” said Kelly Diehl, senior director of science communications for the Morris Animal Foundation. “Almost all golden retriever owners understand this statistic and are passionate about finding a way to reduce the cancer rate in the breed they love.”

Fritz, who practices at Veterinary Referral Associates in Gaithersburg, Md., grew up with golden retrievers, all of whom died of cancer. She said her childhood experience with dogs inspired her to become a veterinary oncologist.

“They are really adorable dogs,” she said. “Honest, loyal and always there for you. Emma was a sweetheart. She slept with my little boy every night and always took care of him and his little sister.

Before Emma died, the family added another golden retriever, Jax, now 11 months old. “Even knowing what I know, professionally and personally, I still wouldn’t have any other race,” Fritz said.

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