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Animal Health Trust genetic studies on the predisposition of Boxers to developing lymphoma and mast cell tumours

Cancer is a major cause of death in dogs, and tumours are twice as common in dogs as in humans. 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. Lymphoma may occur in dogs of any age, but is most common in dogs between 6-9 years old.

Lymphoma is very sensitive to chemotherapy and up to 80% of dogs treated will go into remission, for an average of 12 months. Mast cell tumours are the most common skin cancer in dogs and primarily affect middle-aged and elderly dogs. They display a wide range of severity ranging from the benign to the malignant, but 70% of mast cell tumours can be cured by surgery and local radiotherapy.

Certain breeds of dog are much more likely to develop cancer than other breeds, with some families within these breeds being particularly susceptible. In 2003, the AHT examined the occurrence of lymphoma in 20 breeds within a UK population of 130,684 dogs and found that the incidence of lymphoma in Bullmastiff, Bulldog and Boxer was significantly higher than in other breeds. A further study of the incidence of mast cell tumours in dogs diagnosed at the AHT between 1997 and 1999 identified the highest prevalence in Boxers and Weimaraners.

‘Predisposition’ to developing cancer is thought to arise because of the existence of hereditary (passed on from one generation to the next) gene mutations. These are defects (present in all cells of the body) in some of the specific segments of chromosomes, which contain the information that tells cells what to do and when to do it. In themselves, these defects are insufficient to cause cancer. However, for individuals carrying such ‘predisposing mutations’, the rare events (for example, mistakes in replication of the chromosomes, or exposure to cancer-causing agents, such as tar in tobacco smoke and ultra violet radiation from the sun) that can cause a spontaneous gene mutation in a single cell in the body are more likely to lead to cancer. The inherited susceptibility to cancer probably results from the combined effects of many hereditary gene mutations, each of which confers a low to moderate increase in risk. The risk of developing a cancer is thought to increase according to the number of altered genes inherited.

We are seeking to identify the genes that, when mutated, are associated with the increased risk of Boxers developing lymphoma, or mast cell tumours. Since the Boxer develops these cancers more often than other breeds, the gene mutations that confer the increased risk will be more common than in other breeds, and thus easier to identify. Future work would aim to investigate whether the same gene mutations conferred susceptibility to developing these cancers upon other breeds.

In the long term, we hope that the research will lead to the development of diagnostic tests to identify dogs that carry the gene mutations that confer an increased risk of developing lymphoma, or mast cell tumours, allowing breeders to take these gene mutations into consideration in their breeding programmes. A realistic objective would be to attempt to reduce the incidence of dogs affected with these cancers. Identification of ‘cancer susceptibility genes’ will also improve our understanding of how these tumours develop, thereby ultimately assisting the development of new therapies.

We need to collect DNA samples from large numbers of Boxers, which either have lymphoma, or mast cell tumours (or have had either of these cancers), and Boxers (preferably at least 6 years old) that have not had cancer. Once we have substantial numbers of samples, we can apply for funding to carry out the research that will enable us to identify the ‘cancer susceptibility genes’ contained in the chromosomes (which are made of DNA). DNA can be isolated from cells collected either from the inside of a dog’s cheek, or preferably from a small volume of blood.

Since blood sampling is an invasive procedure, we only ask dog owners to save surplus blood from that collected by a vet as part of a general health check, or for another medical reason. We are also seeking the approval of breed clubs to attend Championship Shows with an Animal Health Trust vet in order to collect blood samples from the dogs of owners who have signed a consent form. On such occasions, blood samples are collected from a dog’s leg, from which hair does not need to be removed, and the vet does not attempt to collect blood from dogs that resist.

If you would like to request cheek swab kits, with which to collect cheek swabs, please contact Dr Mike Starkey (E-mail: mike.starkey@aht.org.uk).

If your vet is able to save blood that is surplus to that collected for a medical reason, please save up to 5ml of whole blood in an EDTA tube. If you submit a blood sample it will be necessary to complete a ‘Blood sample consent form for each sample submitted. Please send blood samples and signed consent forms to: Dr. Mike Starkey, Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.

If you send a blood sample from a country that does not belong to the European Union, send the sample in a package labeled "Animal Pathogen - importation authorised by license number AHZ/2026A/2004/2 issued under the Importation of Animal Pathogens Order 1980".

Unfortunately, we are unable to reimburse you for the cost of sending samples, but we greatly appreciate your invaluable assistance with our proposed important research study.

If you have any questions, or would like further details about the proposed study, please contact Dr Mike Starkey (E-mail: mike.starkey@aht.org.uk).