The Animal Health Trust (http://www.aht.org.uk) is collecting samples for projects seeking to identify the inherited genetic mutations responsible for Boxers having an increased risk of developing gliomas, lymphoma, mammary tumours and mast cell tumours, respectively. The AHT is a member of a consortium of research groups that are conducting the mammary tumour project as part of the LUPA project (http://www.eurolupa.org), a 4 year initiative involving 20 veterinary schools from 12 European countries. In contrast, the studies ongliomas, lymphoma and mast cell tumours are AHT initiatives. With the support of The British Boxer Club, we applied to the Kennel Club Charitable Trust for funding for the study on mast cell tumours, and in September 2009 we were awarded £64,000 for a 1 year project that began on 1st January 2010. We will seek funding for studies on gliomas and lymphoma, respectively, once we have collected sufficient numbers of samples.
Mast cell tumours
Mast cell tumours are the most common skin cancer in dogs, affecting mainly older dogs. Surgery and local radiotherapy are a cure for 70% of tumours, but about 30% of the tumours spread and the dogs require chemotherapy. A study in 2004 of the incidence of mast cell tumours in dogs diagnosed at the AHT between 1997 and 1999 identified a high prevalence in Boxers, Golden Retrievers, Labrador Retrievers, and Weimaraners. At the present time, we have collected samples from 56 Boxers affected with mast cell tumours. However, we continue to need additional samples from Boxers with mast cell tumours, and in particular from dogs that were diagnosed with grade III ('high grade) mast cell tumours. The grade III tumours are the tumours that have a 90% chance of spreading ('metastasising'), and if we are able to collect a sufficient number of samples from Boxers that had grade III mast cell tumours we will be able to attempt to identify the inherited genetic defects that cause an increased risk of developing metastatic mast cell tumours.
Gliomas (also referred to as glial cell tumours) are the second most frequent brain tumour in dogs, and comprise different subtypes with a highly variable response to treatment. Most primary brain tumours develop in older dogs, and dog breeds with short, wide heads have a higher risk of developing gliomas. Clinicians in the AHT Neurology Unit have noted a disproportionately high incidence of Boxers with gliomas, suggesting that the breed carries genetic 'risk factors' for this cancer.
Lymphoma is the most frequent life-threatening cancer in dogs, accounting for up to 20% of all tumours and affecting as many as 24 out of every 100,000 dogs. In the most common form of the disease, cells ('Iymphocytes') derived from the bone marrow become cancerous in one or more lymph glands where they form tumours. Lymphoma may occur in dogs of any age, but is most common in dogs between 6-9 years old. If untreated, death can result within 8-12 weeks of diagnosis. Treatment is usually with chemotherapy, which can increase life expectancy often to about a year, with a small proportion of dogs surviving longer than 2 years. In 2003, the AHT examined the occurrence of lymphoma in 20 breeds within a UK population of 130,684 dogs, who were insured by a pet insurance company between June 1997 and May 1998. The investigation found that the incidence of lymphoma in Bullmastiffs, Bulldogs and Boxers was significantly higher than in other breeds, suggesting, that these breeds carry genetic risk factors.
Mammary tumours are one of the most common tumours to affect older female dogs. Around 60% of mammary tumours are benign, and therefore many dogs can have a good outcome if a tumour is treated with an adequate surgical procedure. Up to 50% of bitches may present with multiple tumours affecting different glands. An increased risk of developing malignant mammary tumours has been reported for several breeds, including Boxers, English Springer Spaniels, German Shepherd Dogs, and Cocker Spaniels, suggesting that these breeds carry genetic risk factors. Early spaying (before the second season) can decrease the risk of tumours developing, and so there are more bitches affected in countries where spaying is not common practice.
In the long term, it is hoped that the 4 research studies will lead to the development of tests to identify Boxers that carry the gene mutations conferring an increased risk of developing the cancer concerned. This information will be useful to vets as it will identify dogs that may benefit from careful monitoring for early detection of cancer, and thereby early treatment. These tests will also assist breeders to reduce the incidence of dogs affected with these cancers. The research will also increase understanding of how these tumours develop, ultimately assisting the development of new therapies.
Canine Epilepsy Studies at the Animal Health Trust
Scientists and clinicians at the Animal Health Trust (http://www.aht.org.uk) are embarking on an exciting project to investigate the genetic basis of epilepsy in the Dog. By combining the expertise of the clinicians to diagnose dogs with idiopathic epilepsy and state of the art genetic research capability we hope to identify the genetic factors involved. If the research is successful the endproduct will be a DNA test that can identify the risk of developing the condition and passing it on to future generations.
At the moment we are in the initial stages and the project is likely to take several years to complete but the first, and arguably most important, step is DNA sample collection. Once sufficient samples have been collected we will analyse genetic markers distributed evenly across the dogs genome to identify those that are shared by all affected dogs and different from those carried by dogs that don't suffer from epilepsy. These markers will point us to the region(s) of the DNA that contains mutation(s) that are responsible for causing epilepsy. Once we have determined the region of DNA that contains the mutations we can undertake additional experiments to identify the mutations themselves.
If we are to be successful we need DNA samples from dogs affected with idiopathic epilepsy and their close relatives, and also from unaffected dogs. The DNA can be provided as a blood sample (if blood is being drawn from your dog for another purpose) or as a simple cheek swab. We would also appreciate a pedigree of all dogs that donate a sample so we can understand how the samples we collect are related to one another. This will help us to understand the mode of inheritance of the condition and how many genes are involved.
All research is undertaken in complete confidence. The identity of all samples submitted to the research effort will be kept confidential and the results from individual dogs will only be shared with the dog's owner(s), once the research has been completed.