Golden retriever illustration

Doggy Diagnosis

Study finds these 3 dog breeds are most at risk for cancer

The findings could also help humans in one surprising way.

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Dogs are called man’s best friend for a good reason, sticking with us through thick and thin over thousands of years.

But according to new research, they might not just bevaluable companions — they could also potentially save our lives from dangerous diseases.

A flat-coated retriever. The researchers studied flat-coated retrievers and other dog breeds to understand their shared genetic risk for blood cancer. Getty

What’s new — Led by a team of French researchers, a study published Thursday in the journal PLOS Genetics identifies genetic risk factors associated with histiocytic sarcoma, a rare blood cancer that occurs in both humans and dogs.

This study focused on three dog breeds, which share similar loci that occur in multiple canine cancers. The dogs include Bernese mountain dogs, Rottweilers, and retrievers — specifically, flat-coated retrievers and golden retrievers.

Through their research, the scientists had a few key takeaways:

  • a previously identified locus, or a gene’s specific location on a chromosome, known as CDKN2A is associated with an increased risk of histiocytic sarcoma
  • the scientists also identified new loci associated with a risk of histiocytic sarcoma on canine chromosomes 2, 5, 14, and 20
  • the researchers concluded that these loci have additive risks for other cancers, such as lymphoma or mast cell

The last finding could have particular implications for studying histiocytic sarcoma in humans, too

In a press statement, the study authors write: “This study took advantage of dog breed predispositions to decipher the genetic bases of histiocytic sarcoma, a rare human cancer.”

A Bernese mountain dog playing. The study found a high risk between certain genes in Bernese mountain dogs and blood cancer.Getty

How they did it — The researchers looked at shared genetic risk for histiocytic sarcoma across the three dog breeds, otherwise known as a genome-wide association study.

Scientists use these studies to scan for disease markers across the DNA of different people — or different dog breeds, in this case — to aid in disease treatment and prevention. In this case, the researchers also used targeted genetic sequencing of specific loci to identify genetic variants linked with cancer.

The authors write in the study: “This study aimed to extend previous studies by deciphering the genetic basis of (histiocytic sarcoma) based on a multi-breed approach.”

This is the largest such genome-wide association study of histiocytic sarcoma risk in dogs.

Digging into the details — The researchers confirmed several risky alleles associated with a greater risk of histiocytic sarcoma.

The researchers found that individual dogs within the breeds that inherited at least 5 out of 6 of these risky alleles on three specific loci — CFA11, CFA5, and CFA14 — had five times greater risk of developing histiocytic sarcoma.

Why it matters — The specific alleles located in the three dog breeds correlate not only with a greater risk of blood cancer, but also lymphoma and other types of cancer.

This additive effect is known as pleiotropy, which occurs when one gene can have several effects in unexpected ways.

Pleiotropy is also a common phenomenon in human cancer research, which makes the study relevant for studying histiocytic sarcoma in humans as well.

The researchers write that the sheer genetic diversity of human cancers makes studying their underlying genetic predisposition “almost impossible in rare cancers” like histiocytic sarcoma.

However, dogs, have been artificially bred in such a way that it’s easier to identify the genetic expression of certain alleles that pose a higher risk for cancer. So, if we can identify these genetic risk factors in dogs, that could be the first step to identifying and treating them in humans, too.

The researchers conclude that research on these three dog breeds “provides a unique opportunity to unravel the genetic basis of this cancer.”

A pair of Rottweilers in a field. The study researchers the link between certain genetic alleles and blood cancer risk in Rottweilers and two other dog breeds. Getty

What’s next — The research promises exciting possibilities — not only for potentially treating these three dog breeds for blood cancer but also humans.

As the researchers write: “Thus, spontaneously affected pet dogs, with breed-specific cancers, provide efficient natural models to identify the genetics underlying several dog-human homologous cancers.”

However, scientists still have some ways to go before we can fully unlock the shared mechanisms underlying blood cancer in these three dog breeds.

For example, the study contains a limited sample of flat-coated retrievers, so future research will need to focus more on the retriever’s genetic similarities to the other two dog breeds studied.

The research also identifies alleles that correlate strongly with multiple kinds of cancer in golden retrievers. But further research is required to determine if Bernese mountain dogs also share these same risky cancer alleles.

Still, for now, we can take comfort in the idea that humans share more in common with our favorite pooches than previously realized — and that similarity might just save us from future cancers.

Abstract: Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.
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