Progress Made in Determination of Heritable Risk Factors For Canine Lymphoma

Raleigh, NC - Researchers have announced that prevalence of B-cell and T-cell lymphomas among certain dog breeds indicates heritable risk (Cancer Research, Vol 65, No. 13, July 2005). This research, led by Drs. Jaime Modiano, University of Colorado Health Sciences Center, and Matthew Breen, North Carolina State University, was possible in part by grants made by the Canine Health Foundation to study lymphoma in several breeds, and has been sponsored by 21 breed clubs, corporations, and individuals.

According to Modiano and Breen, “The predisposition of certain breeds to develop lymphoma has been recognized for a long time, but this is the first indication that the tumors themselves harbor breed-specific genetic abnormalities. This opens new avenues for investigation that will help us to identify specific genes that contribute to the risk of lymphoma in dogs, and possibly in people.”

Cancer risk has long been believed to have heritable components. However, genes that may be causally related to sporadic cancers such as non-Hodgkin’s lymphoma have been difficult to pinpoint. This research shows that the prevalence of B-cell and T-cell lymphomas differs among dog breeds. Additionally, it determined that these different prevalence rates are shared among dog breeds that are closely related. The article in the publication Cancer Research states “…these results indicate that recurrent genetic abnormalities that occur with significantly higher frequency in a single dog breed can assist in the identification of candidate genes that may be associated with the origin or progression of both canine and human cancers.”

Dogs make an excellent model to study heritability factors in cancer. According to the investigators, “The limited level of genetic heterogeneity within dog breeds, combined with the fact that the incidence and lifetime risk of naturally occurring (disease) differs among dog breeds, offers a unique opportunity to identify genetic risk factors that contribute to the pathogenesis of (disease).”

“Canine cancer has long been the top concern among our clubs and individuals,” states president, Wayne Ferguson. “It is so gratifying to see that we are helping to lead the charge against identifying the risk factors and genetic markers for this dreaded disease. In fact, cancer research accounts for more than 30% of the AKC Canine Health Foundation’s total grant allocations in the last 10 years.”

The AKC Canine Health Foundation, founded in 1995 by the American Kennel Club, is the largest nonprofit worldwide to fund health research exclusively for canines. Its goal is to help dogs live longer, healthier lives. Because canines and humans share much of the same genome, much of the research on canine diseases applies to people as well. In this, our tenth anniversary, the AKC Canine Health Foundation is proud to announce it has allocated more than $13 million in canine health research through 52 schools and research institutions for about 275 studies.

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http://www.americanboxerclub.org/2002-grants.html

Active Grant No. 22101: Development of Anti-Canine IL-2R? Antibodies Using CpG Oligodesoxynucleotide Vaccination
Stuart C. Helfand,DVM, University of Wisconsin, Madison.

Sponsor: Nestle Purina Company, American Boxer Charitable Foundation, Golden Retriever Club of America, Golden Retriever Foundation

This protocol could also be called, "the development of a magic bullet". Despite progress in treating canine lymphoma, most affected dogs eventually develop resistance to chemotherapy and succumb to their disease. In human medicine, a molecule on the surface of lymphoma cells, the subunit of the interleukin-2 receptor (IL-2R?). Recently, antibodies have been developed to deliver cellular toxins or radioisotopes directed against the malignant lymphoma cells, a strategy aimed at overcoming drug resistance. This technique is a form of so called immunotherapy which is being widely pursued in the treatment of human cancer. Dr. Hefland has succeeded in isolating the IL-2R molecule in Golden Retrievers and Rottweilers and now proposes a method to develop antibodies against this molecule. These antibodies then could be tagged with an appropriate cellular toxin or radioisotope to specifically target only the malignant lymphoma cells. This could prove to be a powerful tool in both diagnosis, prognosis, and treatment of canine lymphoma.