“All dogs can develop cancer, but goldens have the highest probability,” said Fritz. “We believe they have many cancer-related gene variants. We just haven’t narrowed them down, hence we haven’t been able to target them.”
The Morris Animal Foundation has had an ongoing study in golden retrievers for more than a decade, trying to identify genetic, environmental, nutritional and other factors that influence cancer. And scientists at the University of California at Davis who are seeking to find out 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 enjoyed a life span nearly two years longer than those without it, a significant time difference for a dog. Interestingly, the mutation they identified came from a family of genes linked to cancers, including human ones.
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 radiological services at the UC Davis School of Veterinary Medicine, and co-corresponding author.
“We looked based on how long they lived,” Rebhun said. “The amazing thing is that by looking at how long they lived, the gene variant that popped up is a gene known to be associated with cancer.”
Good dogs and bad variants
More than 300 golden retrievers participated in the study, including Rebhun’s own dog, Jessica. The scientists compared DNA from blood samples of golden retrievers that were alive at 14 to those who died before they were 12. They found that dogs with the gene variant survived longer, on average to age 13.5 years compared to 11.6 years.
Rebhun said the gene appears to have a “good variant” and a “bad variant,” that is, one that promotes survival, the other linked to shorter lives. “Jessie” developed a slow-growing soft tissue sarcoma at 14, but lived until she was 16 ½, he said.
“She had one of the good variants, and one of the bad ones,” he said. “Our theory is that the bad one might contribute to the development of cancer, while the good one staved it off until she was 14.”
The study also found intriguing differences between male and female dogs, raising the possibility that female hormones, such as estrogen, may be involved, he said.
Female dogs with one copy of the bad variant lived significantly shorter times than female dogs that did not have the bad variant. In contrast, there was no difference between male dogs with one copy of the bad variant compared with male dogs that didn’t have it at all.
For male and female dogs, having two copies of the bad variant resulted in significantly shorter lives.
The research “presents some 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 was not involved in the study.
“The findings are tantalizing and like most things in science, lead to 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’s the canine equivalent of a gene found in a family of human genes whose variants are linked to cancer.
In the dog study, the ErbB4 gene variant was related to an increase in life that is equivalent to an additional 12 to 14 years in humans, said geneticist Danika Bannasch, professor of population health and reproduction at UC Davis and co-corresponding author.
This study aims “at one of life’s biggest mysteries, not just in dog science but in human health,” said Elinor Karlsson, director of vertebrate genomics at the Broad Institute of MIT and Harvard, who also was not involved in the research.
“Why do some people live longer than others? Why do some dogs live longer than others?” she said. “We don’t know why, but this study is starting to get at that question.”
ErbB4 variants appear to act in two ways. It can act like an oncogene – which drives cancer – or it can behave like a tumor suppressor gene, which puts the brakes on the disease. Rebhun said it’s unclear what triggers each behavior. “We don’t have the exact mechanism for saying whether this variant is stimulating cancer growth in golden retrievers or prohibiting it, or how it does each,” he said.
The potential of the findings could be significant. Earlier research into a variant of the HER2 gene, which is part of the same family as ErbB4, led to a significant breakthrough in human breast cancer treatment, resulting in a targeted therapy called Herceptin for patients with HER2 positive breast cancer.
Hope for golden retrievers and their humans
Although experts said the practical applications of the study are probably years away, they hope the findings will lead to a test or other diagnostic tool to identify or treat vulnerable dogs — and possibly even humans.
“Dogs and humans share many of the same environmental factors and genes, and they work similarly in both species,” Rebhun said.
He and his colleagues hope to conduct a larger study in golden retrievers and also 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 as much from cancer as goldens.”
The dogs’ cancer risk has done little to diminish their appeal. “They’re simply wonderful dogs, which makes their high cancer rate 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 them lost to cancer. She said her experience with her childhood dogs inspired her to become a veterinary oncologist.
“They are totally lovely dogs,” she said. “Honest, loyal, and always there for you. Emma was a sweetheart. She slept with my little boy every night and always looked out for 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 breed,” Fritz said.