Biochemical markers and genetic risk factors in canine tumors

Abstract: One out of four dogs will develop cancer before the age of 10 years. Many of them will succumb to the disease. Risk factor analysis, tumor prevention, and ways to prognosticate already existing tumors in the individual patient, are important. Canine mammary tumors (CMTs) are the most common type of tumor in intact female dogs and constitute about half of all tumors in female dogs. About half of the CMTs are malignant. The origin of CMTs is considered to be complex, with tumor development likely influenced by both genetic and environmental factors. In Sweden 36% of English Springer spaniels (ESS) are diagnosed with CMTs, suggesting a genetic influence in this breed. Several risk factors predisposing to CMT have been identified, but the majority of inherited risk factors remain unknown. The aim of the research described in this thesis was to study biomarkers, epidemiology and genetic risk factors in canine tumors with the main focus in canine mammary tumors, using a population of a breed at high-risk for this disease in Sweden. In the first study, a study of a serum biomarker in canine tumors, serum thymidine kinase 1 (TK1) -activity in canine malignant lymphoma, leukemia and solid tumors using the standard TK REA and non-radiometric assays was performed. Serum TK1 was proven to be highly effective in diagnosing, prognosticating, and monitoring dogs with hematological neoplasias (lymphoma, leukemia), but the assay was ineffective in detecting TK1 activity in solid tumors such as CMTs. Clinical and histological characteristics of CMTs were described in a population of ESS dogs in Sweden. The reproductive status was shown as an important risk factor for MT development and age of onset and histological subtype affected the survival time after diagnosis of MT-affected dogs. Genetic risk factors for CMTs were further investigated in the following studies. A candidate gene association study in CMTs showed two human breast cancer genes, BRCA1 and BRCA2 that were associated with CMT in ESS dogs. The potential involvement of the major histocompatibility complex (MHC) class II in CMT development was studied and the results indicated diversity of MHC class II haplotypes and identified a haplotype that protected against MT development in ESS dogs. In summary, this thesis provides new information about risk factors for CMT development. The identification of genetic risk factors is critical to improvements in prevention, diagnosis and treatment of these tumors.

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