Canine DNA Reveals New Genes Linked to Gastric Cancer In Humans

Dogs share our homes, our habits and sometimes, our diseases. Gastric cancer is rare in dogs, but when it does strike, it closely resembles gastric cancer in humans: subtle clinical signs, comparable tumor subtypes, late-stage diagnosis and poor outcomes. That similarity, combined with unique genetics, makes purebred dogs a powerful model for studying this devastating disease, which is the fifth most common cancer worldwide.

In a new study published May 30 in the Proceedings of the National Academy of Sciences, a team of Cornell researchers used canine DNA to uncover more than 15 genes linked to gastric cancer.

The study bolsters the idea that dogs – especially purebred populations – are powerful models for studying human diseases, said Jacquelyn Evans, who led the work and is assistant professor at the Baker Institute for Animal Health and faculty associate at the Cornell Riney Canine Health Center and in the Department of Biomedical Sciences at College of Veterinary Medicine (CVM).

"We were able to identify over 15 genome regions that are important for susceptibility to gastric cancer using DNA from fewer than 500 dogs – that's a lot of genes," said Evans. "Studies like this in humans require thousands of DNA samples and still typically uncover fewer genes." This is largely because purebred dogs have limited genetic variation within breeds, allowing key differences between sick and healthy individuals to stand out. The newly identified genes, including some not previously linked to cancer, offer promising new avenues for research into human gastric cancer, Evans said.

The study focused on two dogs breeds disproportionately affected by gastric cancer: the Belgian Tervuren and Belgian sheepdog. Over several years, pet owners, dog breeders and veterinarians in North America and Europe collected blood or cheek swab samples from these breeds and sent them to CVM researchers and colleagues from Utrecht University; the University of California, Davis; Tufts University; and the National Human Genome Research Institute, part of the National Institutes of Health. The CVM researchers include first author Shawna Cook, a postdoctoral associate in the Evans lab, as well as Jessica Hayward, senior research associate in the Department of Biomedical Sciences.

The team analyzed DNA sequences from samples of 200 dogs diagnosed with gastric cancer and 270 healthy controls. They used an approach that allowed them to compare specific DNA sequences between the groups of dogs.

Specifically, Cook looked for differences in how often key DNA bases appeared at different genome sites.

At the sites that are really important for gastric cancer, what we saw is a distinct DNA difference between healthy and sick dogs, and it tells us that genes in this region contribute to developing the disease."

Jacquelyn Evans, assistant professor, Baker Institute for Animal Health

The study revealed 15 genomic regions that appear to determine the lifetime risk for gastric cancer in these dogs. The sites include both known cancer genes like tumor suppressor PTEN, also seen in humans, as well as novel ones that have not previously been associated with the disease, such as PDZRN3. These newly identified genes offer promising avenues for research into human gastric cancer.

The researchers also drew on data from Embark, a canine genetic testing company and a CVM research partner, to compare DNA sequences from Belgian Tervuren and sheepdogs to a third breed, Belgian Malinois, which is closely related but rarely develops gastric cancer. "We wanted to understand what is different about the Malinois, since they're otherwise so genetically similar, and whether they might carry something that protects them from getting gastric cancer," Evans said.

The team identified three important regions, two of which could potentially have a protective effect. These stretches of DNA were uniquely common in Malinois and showed up more frequently in the study's healthy controls.

The researchers hope to translate these insights into practical tools that improve outcomes for dogs. In canines, gastric cancer is usually diagnosed too late for effective treatment. "But with a genetic test, we could screen high-risk dogs earlier and potentially catch the disease while it's still treatable," Evans said. Genetic testing could also help guide breeding decisions to reduce disease prevalence, and some of the newly identified genes may serve as targets for future therapies. If successful in dogs, those treatments might be explored in human clinical trials as well, she said.

The team is now working to collect additional samples to validate their findings for an accurate genetic test and to explore whether specific genes contribute to different gastric cancer subtypes, Evans said. "We're also interested in identifying genes that are dysregulated in the tumors themselves, which could help us zero in on therapeutic targets."

The research was supported in part by the Cornell Richard P. Riney Canine Health Center, the intramural program of the National Human Genome Research Institute, and American and European Belgian shepherd dog breed clubs.