Review Article Breed-Predispositions to Cancer in Pedigree Dogs

Hindawi Publishing Corporation ISRN Veterinary Science Volume 2013, Article ID 941275, 23 pages http://dx.doi.org/10.1155/2013/941275 Review Article Breed-Predispositions to Cancer in Pedigree Dogs Jane M. Dobson Queen’s Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK Correspondence should be addressed to Jane M. Dobson; [email protected] Received 1 October 2012; Accepted 22 October 2012 Academic Editors: F. Napolitano and R. L. Page Copyright © 2013 Jane M. Dobson. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. is paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. 1. Introduction factors, so the aetiology and pathogenesis of canine tumours islikelytobesimilartothatofhumantumours[4–8]. A Cancer is an important disease in dogs and represents one of general comparison of the incidence of canine cancer with the major causes of canine death accounting for 27 of all that of human cancer highlights some striking similarities deaths in purebred dogs in the UK in a recent mortality study and differences [9]. Breast cancer is the most common [1]. is is slightly higher than what previously reported% in malignancy in women and the mammary gland is a common a Danish Kennel club study (14.5 by Proschowesky et al.) site for tumour development in bitches, although the risk is and an earlier UK study (15.7 by Michell) but similar to a reduced in bitches spayed at a young age [10], demonstrating postmortem series of 2000 dogs, in% which 23 of all dogs and the importance of endogenous hormones in the development 45 of dogs over 10 years of% age died of cancer [2]. In the of this disease. In contrast, carcinomas of the prostate, a absence of reliable historical tumour registries,% it is difficult very common condition in men and also associated with to% know whether the prevalence of cancer in dogs is actually hormonal stimulation, is relatively uncommon in dogs and increasing; however a number of factors may contribute to occurs more frequently in neutered dogs [11]. Carcinomas of an increase in the diagnosis of cancer in dogs; as a result of thelungandlargebowel,themostcommonhumantumours improvements in health and welfare animals are living longer excluding breast and prostate, do not feature highly in the and cancer is generally a disease of older age [3]. Advances canine population, whereas so tissue sarcomas, which are in veterinary medicine, particularly diagnostics and higher rare in humans, are relatively common in dogs. expectations of the pet owning public, are likely to result in However, whilst general trends for the occurrence of an increased rate of diagnosis. canine cancers are well established, accurate �gures for As is the case in the human population, many different the frequency of different types of tumours in the canine types of naturally occurring cancer may affect dogs and population are limited. One study of insured dogs from the canine malignancies have been established as strong compar- United Kingdom showed the skin and so tissues to be the ative models for the human disease due to their spontaneous most common sites for tumour-related claims (both benign development and frequency; dogs live in our environment and malignant) with a standardised incidence rate of 1437 and eat similar food and are thus exposed to similar risk per 100,000 dogs/year, followed by mammary, urogenital, 2 ISRN Veterinary Science Incidence of specific types of canine neoplasia indicatorsofbreedsatriskofcancer,butshouldnotbe Mammary regarded as completely de�nitive because the outcome oen carcinoma depends on the breed prevalence within the population at Osteosarcoma risk, which may explain the differences found in studies Lymphoma from different countries. e existence of other inherited diseases or breed-associated problems is a major confounding Soft tissue sarcoma factor: for example the reason the bulldog has an apparent Mast cell low risk of cancer in Table 1 may be due to its short life- tumour expectancy due to other health issues that affect the breed Adenoma [24]. Other limitations of such studies include owner compli- Lipoma ance, bias through nonrandom sampling of the pedigree dog population, and accuracy of owner-reported cause of death. Histiocytoma Furthermore a small number of dogs can seriously bias the 0 50 100 150 200 250 300 350 400 results for numerically small breeds, as demonstrated by the Standardised incidence rate (/100,000 dogs/year) red and white setter in Table 2 and probably the Hungarian wireheriad vizsla, and Welsh terrier in Table 1.However,the Mammary carcinoma Adenoma fact that all these studies consistently show similar overall Osteosarcoma Lipoma breed-related predispositions to development of cancer has Lymphoma Histiocytoma important implications in understanding the aetiology of Soft tissue sarcoma Mast cell tumour cancer as it infers a genetic and heritable component. e dog has a unique population structure with each F 1: Incidence of speci�c types of canine neoplasia. From [12] breed arising from a limited number of founders. e dog (Pink bars denote malignant tumours, blue benign lesions). is believed to have evolved from grey wolves possibly from Europe or the Middle East although interbreeding with local wolf populations clearly occurred elsewhere in the early lymphoid, endocrine, alimentary, and oropharyngeal sites. history of dog lineages [25–27]. Although the wolf dog Canine cutaneous histiocytoma was the most common became domesticated 20–30,000 years ago, and dog types tumour type overall with a standardised incidence rate of were gradually established for guarding, herding, and hunting 337 per 100,000 dog/year, followed by lipoma, adenoma, so purposes, it is only in the past 200 years or so that selective tissue sarcoma, mast cell tumour, and lymphoma (Figure breeding practices have divided the dog population into over 1,[12]). Other epidemiological studies, based on hospital 300 discrete breeds worldwide. e English Kennel Club populations or on surveys of intakes into pathology labora- was established in the Victorian era to meet the demands tories, are largely supportive of these estimates for the canine of the dog breeding Populus, to regulate the registration of population as a whole [13–17], as are recent �gures from a dog breeds, and to establish breed standards. Kennel clubs number of European Tumour Registries [18–20]. in Europe and America still impose strict standards on It is well recognised that differences exist between breeds registration of pedigree dogs requiring that the ancestors of of dog and their risk of developing certain types of cancer each dog must be registered as well. is combined with the but there are few large scale epidemiological studies on the frequent use of popular sires and inbreeding practices means incidence of different types of cancer in the canine population that each breed is a closed, isolated population with virtually which document the variation between breeds. e breeds no gene �ow between breeds [28]. Over the past 200 years with the highest proportional mortality for cancer in the Ken- this practice has resulted in reduced genetic diversity within nel Club/BSAVA study included the following, in descending breeds and greater genetic divergence between breeds. e order: Irish water spaniel, �at-coated retriever, Hungarian average nucleotide heterozygosity when considered across wirehaired vizsla, Bernese mountain dog, rottweiler, Italian dog breeds is comparable to the human population [29], spinone, leonberger, Staffordshire bull terrier, Welsh terrier, but the level of genetic diversity within any single breed is and giant Schnauzer ([1], Table 1). In a study of rates and considerably less than the species as a whole [25] indeed it causes of death in insured dogs in Sweden, Bonnett et al. has been estimated that whilst domestication of wild canid [16] found that the Bernese mountain dog, Irish wolound, populations resulted in a 5 loss of nucleotide diversity, �at-coated retriever, boxer, and Saint Bernard were the �ve breed formation caused a 35 loss [30]. In many breeds breeds of dog with the highest mortality from tumour-related the effective population size% is very small even in normal death. e Bernese, Irish wolound, and leonberger were the times but in some breeds, for example,% the Bernese mountain top three in a subsequent examination of the same data base dog and the leonberger, genetic variation has been further [21]. Bernese mountain dogs, �at-coated retrievers, golden reduced by serious population declines during war or hard retriever, and rottweilers were in the top 5 breeds with over economic times [31]. Mutations in a small number of genes 20 of deaths due to cancer in Denmark [22]. An owner- of large effect are responsible for many breed characteristics; based questionnaire conducted in the UK segregated breeds such selective breeding for exaggerated traits further reduces into% “overrepresented,” “average” and “underrepresented” genetic diversity, and perhaps risks selection of mutations withrespecttodyingofcancerandshowedthesametrends that predispose to disease [25, 32, 33].

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