A Canine Model For Carcinogenesis and Chemoprevention

用于致癌和化学预防的犬模型

• 批准号: 6617733
• 负责人: Elizabeth A McNiel
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617733
• 关键词: Helicobacter; adenocarcinoma; animal genetic material tag; carcinogenesis; chemoprevention; disease /disorder model; dogs; environmental exposure; family genetics; gastroscopy; gene environment interaction; human subject; longitudinal animal study; model design /development; molecular genetics; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nonhuman therapy evaluation; nutrition related neoplasm /cancer; polymerase chain reaction; questionnaires; sample collection; stomach neoplasms; tissue /organ preservation

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： 狗的遗传性癌症综合征是有价值的，但作为研究和预防癌症的资源而被利用不佳。尽管实验室啮齿动物的肿瘤是通过遗传操作，高剂量致癌或直接植入引起的，但宠物犬中天然存在的肿瘤具有类似于人类癌症的病因。重要的是，狗的寿命，潜伏期和肿瘤进展和复发时间小于1/5；因此，在狗中可以相对廉价和迅速地完成结合基因筛查和预防策略的试验。此外，狗的癌症很常见，在组织学和临床上与人类的癌症相似。最近，我们发现，与其他狗相比，Chow Chows的风险是患胃腺癌的10-20倍，这可能是由于常染色体显性遗传的原因。与人类中许多高度渗透性的癌症易感性综合征不同，ChOW会形成肿瘤作为老年人，表明除遗传学外，环境因素在这种癌变中可能很重要。 该应用的目的是建立一种新的动物癌模型，用于研究癌变和预防策略的评估。我们提出了一项研究，以开始表征遗传学，包括遗传模式，以及在食物中的胃癌作用中的环境贡献，包括饮食，环境暴露和螺旋细菌感染。此外，我们将建立将允许该模型用于化学预防剂的资源。这些研究将为更全面的研究提供一个框架，包括对潜在的新型癌症易感基因的映射和表征，基因 - 环境相互作用的机械研究以及对癌症预防策略的研究。这项工作将建立一个范式，用于利用癌症研究中自发发生的犬类癌，这是我们的长期目标。