Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review

Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs.