One Medicine: Dogs, People, Cancer and NC State Center for Comparative Medicine and Translational Research
The numbers are shocking: Experts estimate that almost 50 percent of all dogs over the age of 10 will develop cancer and approximately one in four of all dogs will at some stage in their life develop a cancer. Though veterinarians are providing high quality medical care for dogs with cancer, mysteries related to cause and treatment continue to puzzle researchers.
Genomics Professor Matthew Breen is conducting research on cancer in man’s best friend in his lab at the N.C. State University Center for Comparative Medicine and Translational Research (CCMTR). Breen, who worked on the Human Genome Mapping Project and the Canine Genome Project, believes studying cancer in dogs will not only improve canine treatment therapies but also offer insights into the cause and treatment of human cancers.
“Dogs in this country get as many cancers as people, if not more. The types of
cancer they get are almost identical to what we see in people,” says Breen, a UK researcher who in 2002 relocated his lab to N.C. State as part of the Genomics Initiative. “It is important to recognize that cancers in the dog are spontaneous diseases. Our pet dogs live in our homes. They breathe the same air as we, drink the same water, get on our beds and often eat the foods we eat. When we take them for a walk, they encounter the same herbicide- and insecticide-treated grass we run across. Add to this shared environment the fact that the genome of the dog is 80 to 90 percent similar to that of people, and why wouldn’t dogs and people get the same kinds of cancer?”
However, the much larger incidence of cancers in dogs than in humans is striking, Breen says. “There are 80 million pet dogs in the US; 55 percent of those are purebred dogs. The incidence of cancer in purebred dogs is substantially higher than the corresponding incidence in people. For example, one in five golden retrievers, one of the most popular breeds in the US, is diagnosed with hemangiosarcoma and is likely to die from it. One in eight goldens is diagnosed with and dies from the equivalent of Non-Hodgkin’s lymphoma. In the overall dog population, we estimate 300,000 dogs die from lymphoma each year. That’s 375 deaths per 100,000 dogs in the US. Clearly, the causes can’t be environmental alone. Certain purebred dogs have a genetic susceptibility to certain cancers.”
To better understand this, Breen points back about 15,000 years when human society had not developed beyond nomadic, survival habits. “In those days, wolves probably preyed on young livestock and maybe even people in nomadic camps. Remember Rudyard Kipling’s ‘Just So Stories?’ The humans, fearing the wolf was about to take their land, threw him some meat. He took it and walked away. When a larger predator approached the camp, the wolf saw him as a threat to his livelihood and chased him away. We can imagine that the wolf was the first intruder alert-defense mechanism — not because he liked the people but because he recognized that the two-legged creatures gave him sustenance.”
Eventually wolves became more domesticated, moving into the camps and becoming part of everyday survival in the emerging human society, Breen adds. For thousands of years, humans continued to breed them for function.
Things changed about 400 years ago with the industrial revolution. Rich land and factory owners with more free time began to breed dogs as a hobby because they liked the way they looked, Breen says. “The American Kennel Club now recognizes 173 purebred dogs. Each comes with a breed standard, a description of the physical and behavioral attributes of the dog. At shows, judges assess their condition and appearance against the breed standard to identify the one most resembling that which we desire.”
The inbreeding designed to generate dogs of a desired look resulted in breeds with “restrictive or limited genetic variability,” Breen says. “Unfortunately, through no one’s fault, by restricting their genetic variability, we simultaneously introduced genetic diseases.” In an animal with lots of genetic variations, the animal may inherit a mutated copy of
a gene from one parent but still be healthy because the other copy is probably OK, he adds. “However, in animal populations with very little genetic variability, it is more likely that both parents pass mutated copies of genes to their offspring. As such, there is a greater ‘risk’ of their offspring being affected by a genetic disease, including cancer.”
A good example of that problem is the Bernese mountain dog (see Churchill in the photo with Breen), which typically lives only 7 to 7 ½ years. “Half of Berners in the U.S. die of a kind of cancer to which the breed is highly predisposed,” Breen says.
The most common cancer in dogs is the equivalent of Non-Hodgkin’s lymphoma. Like humans, most dogs develop lymphoma in middle age. “We are trying to identify the genetic differences between cancer subtypes that don’t kill dogs and those that do,” Breen says. “For example, 85-90 percent of dogs diagnosed with lymphoma will respond to chemotherapy and go into remission. However, only 50 percent of these dogs will live beyond nine months. Looking at the genetic differences between the dogs that survived for short times vs. longer times, we developed a prognostic test that now tells us how long a dog diagnosed with lymphoma will stay in remission when treated with standard of care chemotherapy. Since the genetics of human and dog are so similar, we are now looking at human lymphoma patients to evaluate how predictive of survival are the genes identified in the dog – later this year we will know if we can transfer our dog test to become a human test.”
Since the Human Genome Mapping Project began, “we have spent $3 billion over 15 years to generate a reliable sequence of the human genome,” Breen says. “The sequence of the canine genome was generated in 2004, taking only about a year to finish and costing about $50 million.”
Throughout this period of intense research, an important fact has emerged. “The biggest story we’ve uncovered in the process is that people and dogs are extraordinarily similar in a genetic sense,” he says. “This has affected what our lab does now with human cancer research. It takes thousands of human patients with cancer to identify risk factors, but it only takes maybe 100 canine patients to identify these factors in dogs. This is because their genetic makeup is not as ‘noisy’ as that of humans. As such, we can look at the genetics of cancer in dogs to accelerate discoveries that will benefit both dogs and people.”
The U.S. spends a fortune studying cancers in people, but Breen says studying cancer in dogs is a “tremendous, less costly system, a model organism for identifying genes associated with cancer,” he adds. “The dog has been man’s best friend for 15,000 years, but the fact remains that in the 21st century, with lots of new scientific tools to help us understand the cause and progression of cancers, we’re still struggling. I believe the answers to unlocking some of cancer’s most intriguing mysteries about cancer are sitting right beside us.”
In order to “massively accelerate new therapeutic development,” Breen says labs like his need help from people at very difficult times. “I speak to many people who gladly donate tissue and blood samples from dogs that are dying or have died from cancer, knowing that it’s not just from a dog but from a beloved family member. It is very difficult to pluck up the courage to send that sample to the lab. However, folks know that while that sample won’t help their dog, it will help other dogs. We have the technology and the expertise to address the problem, but only through the compassion of owners can we get the sample population to answer the questions.”
Necropsy can cost several hundred dollars and the shipping of samples may be around a hundred dollars, but Breen says he is “pleasantly surprised and humbled” at how supportive dog breeders and owners are of his lab’s work. Some breed clubs offer help and guidance to grief-stricken pet owners who need help working through the donation process. “I’m always amazed at the compassion of owners. It’s a very sad time for all. I keep a box of Kleenex on my desk; I often need them when I’m talking to people about their dogs.”
This article is by Debbie Selinsky and is reprinted from Southern Neighbor magazine.
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Oncology Core and the Clinical Genomics Core of the Center for Comparative Medicine and Translational Research
Breen Laboratory
