Heritable cancer syndromes in dogs are valuable, yet poorly exploited as a resource for the study and prevention of cancer. Whereas tumors in laboratory rodents are induced through genetic manipulation, high dose carcinogen administration or direct implantation, naturally occurring tumors in pet dogs have etiologies similar to human cancers. Importantly, life span, latency periods, and time for tumor progression and recurrence for dogs are less than 1/5 those for people; thus, trials combining genetic screening and preventative strategies can be completed relatively inexpensively and rapidly in dogs. Furthermore, cancer in dogs is common and is histologically and clinically similar to cancer in humans. Recently, we have found that Chow Chows have 10-20 times the risk of developing gastric adenocarcinoma compared to other dogs, probably due to autosomal dominant inheritance. Unlike many highly penetrant cancer susceptibility syndromes in humans, Chows develop tumors as older adults, suggesting that environmental factors, in addition to genetics, may be important in this carcinogenesis. The goal of this application is to establish a new animal cancer model for the study of carcinogenesis and the evaluation of prevention strategies. We propose a study to begin to characterize the genetics, including the mode of inheritance, and the environmental contributions, including diet, environmental exposures, and helicobacter infection, in gastric carcinogenesis in Chow Chows. In addition, we will establish resources that will allow this model to be used in the investigations of chemopreventatives. These investigations will provide a framework for more comprehensive studies, including the mapping and characterization of a potentially novel cancer susceptibility gene, mechanistic investigations of gene-environment interaction, and investigation of cancer prevention strategies. This work will establish a paradigm for utilizing spontaneously occurring canine cancer in cancer research, which is our long-term goal.
| McNiel, Elizabeth A; Carmella, Steven G; Heath, Lori A et al. (2007) Urinary biomarkers to assess exposure of cats to environmental tobacco smoke. Am J Vet Res 68:349-53 |
