Dog Bones Matter Just as Much as Dogs’ Bones
Breed and Body Mass in Osteosarcoma Development
Background
Osteosarcoma is a malignant neoplasm normally found in osteoblasts, cells that oversee the building of bones. DNA mutations arise in these magnificent builders that lead to them building weaker bone than they normally would. Most cases of osteosarcoma are found in the ‘long bones’ of the legs (femur), normally at or around the knee.
Osteosarcoma is labeled according to its anatomical position. Axial osteosarcoma can be found in bones that are ‘outside of the limbs’, like the skull and ribs. Appendicular osteosarcoma occurs at or near the growth plates in between bones. Some of you might know of someone whose dog developed this aggressive form of cancer; maybe it was even your own dog. Believe it or not, dogs are about 15 times more likely to have osteosarcoma than humans.
Summary: Bigger Isn’t Always Better
A UK study sought to determine which breeds of dogs were more likely to develop osteosarcoma. They used anonymous veterinary records in addition to demographic and pathology records in an attempt to identify what puts some dogs at risk for osteosarcoma. What they found was that dogs with a large bone and body mass had a higher risk of developing bone cancer. Rottweilers, Irish Wolfhounds, and Greyhounds were the top three dogs with an increased incidence rate of cancer in this study.
Osteosarcoma isn’t generated from one large, highly penetrant genetic variant, but multiple small, low penetrance genetic variants. Further research suggests that osteosarcoma arises from mutations in genes that are responsible for growth, such as IGF-1 (Insulin Growth Factor-1) locus or errors within the CDKN2A/B (Cyclin-Dependent Kinases) regions. Errors in these genes often result in excessive and rapid long bone growth leading to an increased risk for bone cancer.
On the flip side, researchers also looked at a mutated gene in dogs, autosomal fibroblast growth factor 4 (FGF4), that lives on Chromosome 12. Mutations within this gene often give rise to chondrodystrophy, a disease that results in very short ‘long bones’ and vertebral disc disease. This arises from the premature calcification of the ‘gel-like’ nucleus pulposus layer that is found in vertebral discs, discs of cartilage that lie in between vertebrae and allow for their flexibility. This paper by Parker et al. gives a good explanation of how errors in FGF4 are associated with chondrodystrophy.
Dogs that carry a high rate of this mutation include breeds such as Spaniels and Dachshunds, most of which were associated with ‘protection’ from osteosarcoma according to the UK study. It’s hypothesized that since these bones are not as long as they should be, there is less of a chance that they will incur mutations. These protected breeds have been shown to have the lowest risk of osteosarcoma.
Observing which dogs have a higher predisposition to cancer can help veterinarians encourage regular screenings to detect and possibly treat early bone tumors. By studying the links between chondrodystrophy and protection from osteosarcoma, we could identify genetic variants that are associated with a decreased risk of osteosarcoma. With this information, we can create new ways to diagnose osteosarcoma in dogs as well as therapeutics to treat bone cancer should it arise. Who knows, maybe humans can eventually benefit from these developments.
