Osteosarcoma inheritance in two families of Scottish deerhounds

Abstract

BackgroundOsteosarcoma is the most common neoplastic disease in Scottish Deerhounds. For Deerhounds, a 2007 population-based study concluded that a single dominant genetic factor largely governed disease risk. For Greyhounds, Rottweilers, and Irish Wolfhounds, a 2013 genome-wide association study found multiple genetic markers in each breed, with each marker only weakly associated with the disease.We obtained from two breeders the pedigrees, age (if alive) or age at death, and osteosarcoma status for two families of Scottish Deerhounds, designated Cohorts K and T. A dog was considered unaffected only if it was osteosarcoma-free and at least 8.5 years old. We analyzed the data in two ways, by assuming either a single recessive genetic factor or a single dominant genetic factor with high penetrance.ResultsCohort K contained 54 evaluable dogs representing 12 litters. Cohort T contained 56 evaluable dogs representing eight litters. Osteosarcoma seemed clearly heritable in both cohorts; however, having a parent with osteosarcoma raised a pup’s risk of developing osteosarcoma to 38% for Cohort K but 78% for Cohort T, suggesting the possibility of different genetic risk factors in each cohort. In Cohort K, osteosarcoma inheritance fit well with a single, recessive, autosomal risk factor, although we could not rule out the possibility of a single dominant risk factor with incomplete penetrance. In Cohort T, inheritance could be explained well by a single, dominant, autosomal risk factor but was inconsistent with recessive expression.ConclusionsInheritance of osteosarcoma in two Scottish Deerhound families could be explained well by a single genetic risk factor residing on an autosome, consistent with a 2007 report. In one family, inheritance was consistent with dominant expression, as previously reported. In the other family, inheritance fit better with recessive expression, although the possibility of a dominant genetic factor influenced by one or more other genetic factors could not be ruled out. In either case, the results suggest that there may be at least two different genetic risk factors for osteosarcoma in Deerhounds.

Demographic characteristics, site and phylogenetic distribution of dogs with appendicular osteosarcoma: 744 dogs (2000-2015)

“…[33] A single autosomal genetic risk factor for OS has been identified in Scottish deerhounds. [32, 39] These studies, together with a study documenting that breed-based genetic backgrounds affect the tumor karyotypes in canine OS, suggest a strong contribution of the genetic background to the development of the OS phenotype in these breeds. [30] However, there is also argument that the prevalence of OS in large and giant breed dogs may be due to size instead of breed—a case in point being that even though greyhounds and whippets are in the same phylogenetic microsatellite cluster, disease prevalence is very different between the 2 breeds, with the greyhound much more commonly affected.…”

Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study

“…Findings from canine Genome Wide Association Studies (GWAS) of osteosarcoma imply that both modes of inheritance may apply for osteosarcoma risk alleles, and such studies have so far identified risk-associated polymorphisms at the Insulin Growth Factor-1 (IGF-1) locus, which is associated with large body size, and at other loci, such as the Cyclin Dependent Kinase CDKN2A/B region [ 4 , 7 , 10 , 11 , 13 ]. However, only Irish Wolfhounds, Rottweilers and Greyhounds have been included in existing canine osteosarcoma GWAS, meaning that alternative causal variants in other breeds could have been missed while, to-date, protected breeds have been ignored altogether [ 10 , 13 , 16 ]. Overall, the breed-associated genetics of osteosarcoma need to be examined in more detail in order to facilitate the discovery of novel osteosarcoma risk-associated genetic variants [ 17 – 19 ].…”

“…This means that large breed genetics are necessary but not sufficient to induce osteosarcoma. However, non-genetic risk factors for canine osteosarcoma are poorly understood, and the identification of breeds predisposed to, and protected from, osteosarcoma will generate hypotheses for research in this field [ 16 , 20 ]. In humans, osteosarcoma is rare, affecting 3 individuals per million in the United States each year.…”

“…Osteosarcoma of all anatomical sites was included in this study. The primary hypothesis of the current study was that, based on previous studies, the odds of osteosarcoma are higher amongst specific breeds such as Rottweilers, Scottish Deerhounds, Wolfhounds, Greyhounds and Golden Retrievers compared with crossbreds [ 4 , 5 , 16 ]. Furthermore, it was hypothesised that purebred dogs in general have higher odds of osteosarcoma than crossbreds, since crossbred dogs made up only 19.2% of the total osteosarcoma case population in one study [ 5 ].…”

Dog Breeds and Body Conformations with Predisposition to Osteosarcoma in the UK: A Case-Control Study

“…It was determined that a study with 1756 cases and 905,211 controls would give >99.99% power to detect differences in the odds of osteosarcoma between the Rottweiler (reported to be the most predisposed breed in previous studies) and crossbreeds ( [58] with methodology from [59] table 6.3). This calculation was based on a previously reported osteosarcoma prevalence of 0.03% amongst crossbreeds and 1.14% amongst Rottweilers, with Rottweilers comprising 1.17% of UK dogs [60,61].…”