New Insights from Canine Genetics Reveal Genes Linked to Human Gastric Cancer

Dogs and humans share more than just our homes and habits; they also share certain genetic vulnerabilities. Although gastric cancer is uncommon in dogs, when it occurs, it closely mimics the form found in humans. It presents subtle clinical signs, various tumor subtypes, is frequently diagnosed late, and often results in poor outcomes. This remarkable similarity, combined with the genetic traits unique to purebred dogs, positions them as invaluable models for studying this serious disease, which ranks as the fifth most common cancer globally.

In a groundbreaking study published on May 30 in the Proceedings of the National Academy of Sciences, researchers from Cornell University utilized canine DNA to identify over 15 genetic regions associated with gastric cancer susceptibility. Led by Assistant Professor Jacquelyn Evans, the team demonstrated that studying the genomes of fewer than 500 dogs could uncover significant genetic factors, highlighting the efficiency of canine models in cancer research—a process that in humans would typically involve thousands of samples with fewer discoveries.

The study capitalized on the limited genetic variation within specific breeds, such as the Belgian Tervuren and Belgian sheepdog, both notably affected by gastric cancer. Samples were collected from pet owners, breeders, and veterinarians across North America and Europe and analyzed in collaboration with several institutions, including Utrecht University, UC Davis, Tufts University, and the NIH. The researchers examined DNA from 200 dogs diagnosed with gastric cancer and 270 healthy controls, focusing on differences in DNA sequences at key genome sites. This approach led to the identification of 15 genomic regions influencing the risk of developing gastric cancer.

Among these regions were known cancer-related genes like PTEN, a tumor suppressor also relevant in humans, as well as novel genes such as PDZRN3, which had not previously been linked to this disease. The team also compared genetic data from affected breeds with that from the Belgian Malinois—a related breed that rarely develops gastric cancer—uncovering three regions that might confer protective effects, with two showing higher prevalence in healthy dogs.

These discoveries open promising research pathways for human gastric cancer, especially as the identified genes could serve as targets for future therapies. The researchers envision developing genetic tests to identify high-risk dogs early, allowing for timely intervention and better outcomes. Moreover, these findings could inform breeding strategies to reduce disease prevalence and contribute to developing novel treatments that might someday benefit human patients.

Moving forward, the team plans to validate their genetic findings further and explore how specific genes influence different subtypes of gastric cancer, including those deregulated within tumors themselves, with the goal of pinpointing potential therapeutic targets.

This research underscores the significant role dogs can play in advancing our understanding of complex diseases and highlights the potential for cross-species genetic studies to impact both veterinary and human medicine.