Cancer is an important disease in pet dogs and is one of the major causes of death in insured dogs (Bonnett et al, 1997, Michell, 1999).
In comparison with the incidence of human cancer there are both some striking similarities and differences. Breast cancer is the most common malignancy in women and the mammary gland is a common site for tumor development in bitches. However carcinomas of the lung, large bowel and prostate, the most common human tumors excluding breast, do not feature highly in the canine population.
Accurate figures for the incidence of tumors in the canine population are hard to come by but a study of insured dogs in the UK, showed the skin and soft tissues were the most common sites for tumor development with a standardized incidence rate of 1437 per 100,000 dog / year, followed by mammary, urogenital, lymphoid, endocrine, alimentary and oropharyngeal. Canine cutaneous histiocytoma was the most common single tumor type with a standardized incidence rate of 337 per 100,000 dog / year, followed by lipoma, adenoma, soft tissue sarcoma, mast cell tumor, and lymphosarcoma (Dobson et al, 2002).
It is well recognized that differences exist between breeds of dog and their risk of developing certain types of cancer but there are few large scale epidemiological studies on the incidence of different types of cancer in the canine population and its variation between breeds.
In a study of rates and causes of death in insured dogs in Sweden, Bonnett et al(1997) found that the Bernese mountain dog , Irish wolfhound , Flat-coated retriever , Boxer and St Bernard were the five breeds of dog with the highest mortality from tumor related death. Bernese Mountain dogs, Flat-coated retrievers, Golden retriever and Rottweilers were in the top 5 breeds with over 20% of deaths due to cancer in Denmark (Proschowsky et al, 2003). An owner based questionnaire conducted in the UK segregated breeds into "Over-represented", "Average" and "Under-represented" with respect to dying of cancer (Michell, 1999). These population based studies provide useful indicators to breeds at risk of cancer, but should not be regarded as completely definitive because the outcome often depends on the structure of the population at risk with respect to breed, which explains the differences found in studies from different countries. Also one or two dogs can seriously sway the results for numerically small breeds, as demonstrated by the red and white setter in . However, the fact that there are undoubtedly breed-related predispositions to development of cancer has important implications in understanding the etiology of cancer as it infers a possible genetic, heritable component.
Of the breeds listed above and included as Over-represented in , some have been associated with specific tumor types, eg Bernese mountain dog - disseminated histocytic sarcoma (malignant histiocytosis) , Irish wolfhound - osteosarcoma , and others with a higher risk of tumors in general, eg Boxer, Golden retriever, Rottweiler. This observation also has important genetic implications, suggesting that some breeds may be like the rare human Li-Fraumeni syndrome where a germ line mutation in a tumor suppressor gene (p53 in Li-Fraumeni syndrome) results in a hereditary predisposition to certain forms of cancer (Tabori & Malkin, 2008) whereas other breeds may have a more specific genetic abnormality leading to a particular type of tumor.
Two breeds in which histiocytic tumors have been repeatedly documented and in which detailed genetic studies are in progress are the Bernese mountain dog and the Flat-coated retriever.
Flat-coated retriever
A high incidence of an aggressive, poorly differentiated soft tissue sarcoma has been documented in the Flat-coated retriever, accounting for over half of the malignant tumors and over one quarter of all submission to a histopathological study of tumors in the breed (Morris et al, 2000). Because these tumors lack features of differentiation to allow their classification according to their tissue of origin, over time they have been variably classified as malignant fibrous histiocytoma, malignant histiocytosis or just undifferentiated sarcoma (Morris et al, 2002, Kerlin & Hendrich 1996).
Recently histologically similar tumors in other breeds have been shown to have an immunophenotype consistent with a myeloid dendritic cell origin, leading to the term "histiocytic sarcoma". Localized histiocytic sarcoma describes those lesions which present as solitary masses and disseminated histiocytic sarcoma, those that present with multifocal lesions (Affolter & Moore, 2002). Breeds commonly affected in this report were Rottweiler, Bernese mountain dogs and Retrievers. In Flat-coated retrievers these are aggressive and malignant tumors with 11 of 26 (42%) dogs in a cohort study having confirmed metastases or disseminated, multifocal disease at the time of death. Pedigree analysis has shown familial links and two areas of chromosome (implicated by genome wide analysis) are currently being investigated.
Bernese Mountain dog
Formerly referred to "malignant" and "systemic" histiocytosis , histiocytic disease has also been well documented in the Bernese mountain dog. A study conducted in America showed that histiocytosis accounted for 25.4 % of 500 tumors in the Bernese and analysis of the pedigrees of 127 cases showed the trait to be inherited with a polygenic mode of inheritance and calculated heritability to be 0.298 (Padgett et al, 1993). Genomic analysis is currently being conducted in America in an attempt to identify the genetic basis for this disease.
More general breed predispositions are documented for most of the more common canine tumors such as mast cell tumors , lymphoma and brain tumors .
Osteosarcoma is the most common malignant tumor of bone in dogs and mainly affects the large and giant breeds. The predilection for the tumor to develop at metaphyseal region of long bones , especially the distal radius and proximal humerus, correlates with weight bearing and rapid bone growth during early development, bone stress due to weight bearing (possibly resulting in miocrofractures) are implicated in the etiology of these tumors. However, there may also be a genetic predisposition. A familial incidence has been reported in Rottweilers and St Bernards and more recently, a study modeling the transmission of osteosarcoma in a population of over 1000 Scottish deerhounds estimated heritability at 0.69. Modeling suggested that a major gene with dominant effect would explain the pattern of transmission (Phillips et al, 2007). Irish wolfhounds, Great Danes , Greyhounds and Bull mastiffs are among other large / giant breeds reported to be at risk of osteosarcoma of the long bone.
Lymphoma is the most common hematopoietic malignancy in the dog. Dog breed has been shown to play a role in the epidemiology of lymphoma with several studies showing a significantly higher relative risk for Boxers compared to other breeds (Arnesen et al, 2001).
Other breeds identified with increased relative risk include: Basset hound , St Bernard, Scottish Terrier , Airedale terrier , Bulldog , Bouvier des Flandres , Labrador retriever and Rottweiler (Priester & McKay, 1980, Teske, 1994). A high incidence has also been reported in 3 households of bull mastiffs (Onions, 1984).
Interrogation of the data on a population of insured dogs in the UK showed a significant breed effect with the Boxer, Bulldog and Bull mastiff breeds all having a high incidence of lymphoma (Edwards et al, 2003). It has recently been shown that the prevalence of subtypes of lymphoma also varies with breed or breed group, with Bassets, Border collies , Cocker spaniel , Doberman pinschers , Scottish terriers and Standard Schnauzers having an elevated risk of B cell tumors in contrast to Airedale terriers, Cavalier King Charles spaniel , Irish wolfhound, Shih Tzu , Siberian husky and Yorkshire terrier which have an elevated risk of T cell tumors. Because it is retained in related breed groups (eg Spitz-type dogs and Asian "lap" dogs) the elevated risk for T cell lymphoproliferative disease may have arisen ancestrally, whereas increased risk of B cell disease may stem from different risk factors or combinations which arose during the process of breed selection (Modiano et al, 2005). Using Comparative Genomic Hybridisation (CGH) the same study investigated patterns of chromosomal gains and losses in Golden Retriever lymphomas. Golden retrievers had a prevalence ration of 1 : 1 B cell / T cell lymphoma. It was found that unique patterns of chromosomal gains and losses segregated specifically with B cell and T cell tumors, indicating that consistent genetic abnormalities are associated with different tumor types and thus lending weight to the hypothesis that there is a heritable risk for development of canine lymphoma.
Mast cell tumors (MCTs) are common tumors of the canine skin, estimated to represent up to 20 percent of all skin tumors in this species (Dorn et al,1968).
In the UK, MCT is the second most common canine malignancy, after soft tissue sarcoma with an incidence of 129 per 100,000 insured dogs per year (Dobson et al, 2002). The Boxer and Bull dog breeds including Bull mastiffs, Boston terriers and Staffordshire bull terriers are reported to show an increased risk of developing MCT and it has been postulated that this might be linked to a common ancestry (Peters, 1969). Rhodesian ridgebacks , Pugs , Weimaraners , Labrador retrievers, Beagles , and Golden retrievers have also been reported to be at increased risk (Goldschmidt & Shofer, 1992).
Mast cell tumors show very variable clinical behavior and interestingly this may be influenced by breed. Although Boxer dogs and Bulldog breeds are at higher risk of developing MCTs, these dogs tend to have less aggressive tumors, as is also the case for Pug dogs (McNeil et al, 2006).
Labrador retrievers tend to have more aggressive tumors and Golden retrievers are at risk of developing multiple tumors (Murphy et al, 2006).
Intracranial neoplasia is quite well described in the dog where the most common primary CNS tumor is meningioma , followed by glial tumors (astocytoma and oligodenroglioma). Choroids plexus tumous, medulloblastoma, neuroblastoma and ependymomas occur less frequently.
In a post mortem study of 173 dogs, Golden retrievers and Boxers were at increased risk to develop primary intracranial tumors relative to their frequency in the general Hospital population (Snyder et al, 2006). Brachycephalic breeds have previously been reported to be prone to development of glioma, but in this study only Boxers and Boston terriers were more likely to have an astrocytoma, oligodenroglioma or undifferentiated glioma than another type of primary intracranial neoplasm.
Most of this review has focused discussion on the breeds of dog associated with an increased risk of developing cancer and breed associations recognized in common tumors. Certain breeds or types of dog have been associated with predilections to less common tumors, eg squamous cell carcinoma of the digit in large black dogs including giant Schnauzers and Standard Poodles , anal sac gland carcinoma in Cocker spaniels (Polton et al, 2006), and gastric carcinoma in Rough collies and Belgian shepherd dogs (Sullivan et al, 1987, Scanzian et al, 1991 ).
The domestic dog has been bred selectively for many years to accentuate traits that are desirable in the eyes of the breeder. The fact that the resulting different breeds of dog apparently have different predilections to development of different tumors is not only interesting but could provide a very important insight into the genetic etiology of many forms of cancer. Well designed and conducted population based studies into breed-related cancers would provide an important platform to take forward future genetic research.
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Other sources of information
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Vetstream contributor(s)
Ms Jane Dobson MA DVetMed DipECVIM-CA MRCVS
Ms Suzanne Murphy BVM&S MSc(Clin Onc) DipECVIM-CA(Oncology) MRCVS European and Royal College Recognised Specialist in Small Animal Oncology
