In September, Sarah Fritz lost her six-year-old dog, Emma, to a particularly aggressive cancer called angiosarcoma. As a pet parent, she was heartbroken. As a veterinary oncologist, she was frustrated.
What golden retrievers teach us about cancer
“All dogs can get cancer, but golden retrievers have the highest probability,” Fritz said. “We think they have several genetic variants associated with cancer. We haven’t narrowed them down, so we haven’t been able to target them.”
But this may change. Scientists are studying this popular breed, both as help dogs and To learn more about human cancers. Dogs and humans share most of the same genes.
The Morris Animal Foundation has conducted an ongoing study of golden retrievers for more than a decade, trying to determine the genetic, environmental, dietary and other factors that influence cancer. Scientists at the University of California, Davis, seeking 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 nearly two years longer lives than those without it, a significant time difference for dogs. Interestingly, the mutation they identified came from a gene family associated with cancer, including human cancer.
The UC Davis researchers took an unusual approach in that “we didn’t look for genes associated with cancer,” said Robert Ribhun, a professor of surgical and radiological services at the UC Davis School of Veterinary Medicine and a co-author.
“We looked based on how long they lived,” Ribhun said. “The amazing thing is that given how long they lived, the genetic variant that emerged was a gene known to be associated with cancer.”
Good dogs and bad variants
More than 300 golden retrievers participated in the study, including Ribhun’s dog, Jessica. Scientists compared DNA taken from blood samples of golden retrievers that were alive at 14 years old with those who died before they were 12 years old. They found that dogs carrying the genetic variant lived longer, with an average lifespan of 13.5 years compared to 11.6 years.
The gene appears to have a “good variant” and a “bad variant,” meaning one promotes survival and the other is associated with shorter life, Ribhun said. He said Jessie had slow-growing soft tissue sarcoma when she was 14, but lived to be 16-and-a-half.
“She had one good choice and one bad choice,” he said. “Our theory is that the bad person may have contributed to the development of cancer, while the good person managed to avoid getting it until she was 14.”
The study also found interesting differences between male and female dogs, raising the possibility that female hormones, such as estrogen, are involved, he said.
Female dogs who had one copy of the bad variant lived much shorter lives than female dogs who did not have the bad variant. In contrast, there was no difference between male dogs that had one copy of the bad variant compared to male dogs that did not have it at all.
For male and female dogs, having two copies of the bad variant resulted in a much shorter life.
The research “provides some compelling evidence that this variant is associated with the longevity of golden retrievers,” said Noah Snyder-Mackler, an assistant professor in the College of Life Sciences at Arizona State University, who was not involved in the study.
“The results are puzzling, and like most things in science, they raise more questions than they answer,” he said.
A family of cancer genes in dogs and people
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 in the human gene family whose variants are linked to cancer.
In the dog study, the ErbB4 gene variant was associated with an increase in lifespan equivalent to an additional 12 to 14 years in humans, said geneticist Danica Banach, a professor of population and reproductive health at UC Davis and co-author.
This study aims to “solve one of life’s great mysteries, not only in canine science but also in human health,” said Elinor Carlson, director of vertebrate genomics at the Broad Institute of MIT and Harvard, who was also not involved in the research.
“Why do some people live longer than others? Why do some dogs live longer than others? We don’t know why, but this study begins to answer that question,” she said.
ErbB4 variants appear to work in two ways. It can act like an oncogene – which drives cancer – or it can act like a tumor suppressor gene, which suppresses disease. It’s unclear what triggers each behavior, Ribhun said. “We do not have an exact mechanism to determine whether or how this variant stimulates cancer growth in golden dogs or blocks it,” he said.
The potential outcomes can be significant. Previous research on a variant of the HER2 gene, which is part of the same ErbB4 family, has led to major advances in the treatment of human breast cancer, leading to a targeted therapy called Herceptin for patients with HER2-positive breast cancer.
Hope for Golden Retrievers and their humans
Although experts said practical applications of the study may be years away, they hope the findings could lead to another test or 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 function similarly in both species,” Ribhun said.
He and his colleagues hope to conduct a larger study on golden retrievers as well as examine other breeds.
“Maybe we will find something else that increases longevity in other breeds,” he said. “We also want to look at this variant in other breeds that don’t die from cancer such as Goldens.”
The risk of cancer in dogs has done little to diminish their appeal. “They are simply amazing dogs, which makes their high cancer incidence particularly tragic,” said Kelly Diehl, director of science communications at Morris Animal Foundation. “Almost all Golden Retriever owners understand this statistic and are excited to find a way to reduce the incidence of cancer in the breed they love.”
Fritz, who works at Veterinary Referral Associates in Gaithersburg, Md., grew up with golden retrievers, all of whom he lost to cancer. She said her experiences with her childhood dogs inspired her to become a veterinary oncologist.
“They are absolutely beautiful dogs,” she said. “Honesty, loyal and always there for you. Emma was a sweetheart. She slept with my little boy every night and always looked after him and his little sister.”
Before Emma died, the family added another golden retriever, Jax, who is now 11 months old. “Even knowing what I know, both professionally and personally, I still don’t have any other breed,” Fritz said.
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