Investigations of Asbestos-Related Diseases

描述(由申请人提供)： 儿童遗传易感性与环境暴露的关系 疾病的发展多年来一直被认为是假说。它还 假设DNA序列中的遗传差异有助于 表型变异，影响个体患病风险和反应 对环境的影响。研究人员提议设计新的技术来 研究单核苷酸多态(SNPs)在高危人群中的作用 石棉暴露与石棉相关疾病发展的关系 疾病。这个假设是，通过将一个跨学科的 团队和外部专家，可以创造新的流行病学技术来 更高效、更可靠地开发新的研究设计。该机制可实现 实现这一目标就是为多学科创造机会 互动，以及与研究社区的互动。科学的 假设是参与石棉反应途径的基因中的SNPs 可能负责赋予敏感或耐药表型 石棉引起的人类疾病发展。 为了检验假设，并实现提案的目标， 调查人员将：(1)在彼此的学科中教育团队成员， (2)发展新的分子流行病学技术来调查 环境暴露与其易感性之间的联系 暴露引起的疾病，(3)建立相互沟通的机制 研究人群和调查人员，(4)利用试点项目开发 初步数据，以及(5)准备和提交RO1拨款提案，使用 该团队开发的新方法得到了初步数据的验证 从试点项目中获得。 通过这些机制，调查人员将建立将 使他们能够对以下各项风险进行创新的调查 暴露于石棉后的疾病发展。这项提议的目标是 准备RO1应用程序来解决此问题，并具备强大的 已经开发出尽可能最好的调查方法的团队。在 过程中，他们将确定对易感性重要的多态 和/或石棉反应途径中涉及的基因的抗性，对于 提高对这些机制的理解的最终目的 肺部疾病。

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.