Investigations of Asbestos-Related Diseases

石棉相关疾病的调查

• 批准号: 6625827
• 负责人: Elizabeth A Putnam
• 金额: $ 20.63万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-27 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625827
• 关键词: asbestos; blood chemistry; clinical research; disease /disorder etiology; disease /disorder proneness /risk; environment related neoplasm /cancer; environmental contamination; environmental exposure; environmental health; experimental designs; gel electrophoresis; gene expression; genetic polymorphism; genetic susceptibility; human subject; meeting /conference /symposium; molecular genetics; nucleic acid sequence; nucleotides; pathologic process; phenotype; polymerase chain reaction; pulmonary fibrosis /granuloma; respiratory disorder epidemiology

DESCRIPTION (provided by applicant): The relationship between genetic susceptibility and environmental exposure in the development of disease has been hypothesized for many years. It has also been hypothesized that inherited differences in DNA sequence contribute to phenotypic variation, influencing an individual's risk of disease and response to the environment. The investigators propose to design novel techniques to investigate the role of single nucleotide polymorphisms (SNPs) in the association of asbestos exposure and the development of asbestos-related diseases. The hypothesis is that by bringing together an interdisciplinary team and outside experts, new epidemiological techniques can be created to more efficiently and reliably develop a novel study design. The mechanism to achieve this goal is to create opportunities for multidisciplinary interaction, as well as interaction with the study community. The scientific hypothesis is that SNPs in the genes involved in the asbestos-response pathway may be responsible for conferring sensitive or resistant phenotypes to asbestos-induced disease development in humans. To test the hypotheses, and to achieve the goals of the proposal, the investigators will: (1) educate the team members in each other's disciplines, (2) develop new molecular epidemiology techniques to investigate the connection between environmental exposure and susceptibility to exposure-induced diseases, (3) develop mechanisms for communication between study populations and investigators, (4) use pilot projects to develop preliminary data, and (5) prepare and submit a RO1 grant proposal using the novel methods developed by the team as validated by the preliminary data obtained from the pilot projects. Through these mechanisms, the investigators will establish the tools that will enable them to perform innovative investigations of the individual risks of disease development after asbestos exposure. The goal of this proposal is to prepare a RO1 application to address this question, having in place a strong team that has developed the best investigative methods possible. In the process, they will determine the polymorphisms important for susceptibility and/or resistance in genes involved in the asbestos-response pathway, for the ultimate purpose of improving the understanding of the mechanisms of these lung diseases.

描述（由申请人提供）： 遗传易感性与环境暴露的关系 多年来人们一直对疾病的发展提出假设。 它还具有 据推测，DNA 序列的遗传差异有助于 表型变异，影响个体的疾病风险和反应 对环境。 研究人员建议设计新颖的技术 研究单核苷酸多态性 (SNP) 在 石棉接触与石棉相关疾病发展的关系 疾病。 该假设是，通过汇集跨学科 团队和外部专家，可以创建新的流行病学技术 更有效、更可靠地开发新颖的研究设计。 该机制旨在 实现这一目标的关键是为多学科创造机会 互动，以及与学习社区的互动。 科学的 假设是参与石棉反应途径的基因中的 S​​NP 可能负责赋予敏感或抗性表型 石棉引起的人类疾病的发展。 为了检验假设并实现提案的目标， 调查人员将： (1) 对团队成员进行彼此学科方面的教育， (2) 开发新的分子流行病学技术来研究 环境暴露与易感性之间的联系 暴露诱发的疾病，（3）建立相互之间的沟通机制 研究人群和研究者，(4) 使用试点项目来开发 初步数据，以及 (5) 使用 团队开发的新方法经初步数据验证 从试点项目中获得。 通过这些机制，研究人员将建立工具 使他们能够对个人风险进行创新调查 接触石棉后疾病的发展。 该提案的目标是 准备一份 RO1 申请来解决这个问题，并有一个强有力的 开发出最佳调查方法的团队。 在 过程中，他们将确定对易感性重要的多态性 和/或参与石棉反应途径的基因的抗性，对于 最终目的是提高对这些机制的理解 肺部疾病。