Risk of Leukemia after Protracted Exposures to Low Doses of Ionizing Radiation

长期暴露于低剂量电离辐射后患白血病的风险

• 批准号: 7894332
• 负责人: Lydia B Zablotska
• 金额: $ 16.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894332
• 关键词: Address; Age; Area; Background Radiation; Biological; Biological Markers; Biological Markers; Biometry; Cells; Chromosomal translocation; Chromosomes, Human, Pair 11; Cohort Studies; Comprehensive Cancer Center; Cytogenetics; Data; Development; Diagnostic; Diagnostic radiologic examination; Dose; Dose-Rate; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Ethics; Exposure to; Family; Fellowship; Fluorescent in Situ Hybridization; Fluoroscopy; Funding; Gender; General Population; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic screening method; Goals; Grant; Growth; Health; Human; Human Genetics; Individual; Institutes; Interview; Ionizing radiation; Knowledge; Laboratories; Life; Low Dose Radiation; Malignant Neoplasms; Manuscripts; Medical center; Mentors; Methods; Micronucleus Tests; Molecular Epidemiology; Names; Nuclear Power Plants; Nucleic Acid Regulatory Sequences; Occupational; Occupational Exposure; Oncogenes; Patients; Persons; Phase; Population; Predisposition; Preparation; Prevention strategy; Procedures; Public Health; Questionnaires; RUNX1 gene; Radiation; Radiation therapy; Radiation-Induced Leukemia; Refuse Disposal; Research; Research Methodology; Research Personnel; Research Training; Resources; Risk; Risk Estimate; Role; Rotation; Safety; Saliva; Sampling; Scanning; Schools; Site; Statistical Models; Study Subject; Testing; Time; Training; Training Programs; United States National Institutes of Health; Writing; X-Ray Computed Tomography; base; cancer epidemiology; carcinogenesis; career; design; gene environment interaction; improved; interdisciplinary approach; interest; leukemia; leukemogenesis; meetings; multidisciplinary; radiation effect; skills

DESCRIPTION (provided by applicant): Background: Large groups of the U.S. population come in contact with small doses of radiation through occupational exposures or from background radiation. Additional radiation exposures come from the recent rise in utilization of diagnostic radiology examinations such as x-rays and computed tomography scans. Public's concern about the short and long-term health effects of exposure to radiation, especially leukemia, one of the cancers most susceptible to induction by radiation, is further fueled by proposals to build new nuclear power plants and radiation waste disposal sites. While the effects of high and moderate doses of ionizing radiation on leukemia have been shown in many studies, the effects of lower doses are not clear. To conduct research in this area and to develop my scientific career, I need additional training and mentoring in four target areas, including design and conduct of epidemiological studies, research methods in genetic and molecular epidemiology, advanced statistical training to analyze radiation-related risks and gene-environment interactions, and general training in the ethical conduct of scientific research, manuscript writing and grant preparation. Objective: We propose to examine the association between exposures to low doses of ionizing radiation and risk of leukemia and to assess the role of environmental and genetic factors in carcinogenesis from a new multidisciplinary perspective. The overall scientific objective is to expand the existing body of research on radiation-related risks of leukemia and the public health objective is to quantify such risks, interpret them for the setting of radiation safety limits, inform those exposed to radiation, as well as the general public, and develop preventive strategies. My personal goal is to use the resources of the Department of Epidemiology and Biostatistics, the Institute for Human Genetics and the Helen Diller Family Comprehensive Cancer Center at UCSF and my team of outstanding mentors to become an independent researcher in radiation cancer epidemiology. My long-term goal is to integrate knowledge of epidemiological methods, statistical modeling, and molecular epidemiology in the search for susceptibility factors of radiation exposures. Research and Training Plan: In the first of the three proposed studies (Radiation Biomarkers study), we propose to use various cytogenetic tests to analyze buccal cells previously collected from Chornobyl clean-up workers for lasting effects of radiation exposure. In addition, we will collect new samples of saliva and correlate radiation damage with doses estimated from questionnaires by the RADRUE method. In the second study (Gene Polymorphism study), new information on the biological mechanism of leukemogenesis after radiation exposure would be obtained by conducting genetic tests of two oncogenes (AML1 and MLL) known to be associated both with ionizing radiation exposure and with increased risk of leukemia. In the Risk Analysis study, data from the Leukemia study of Chornobyl clean-up workers will be combined with the data from the Canadian Fluoroscopy Cohort study to estimate radiation-dependent risks of leukemia and to compare them to the risks predicted from high-dose studies. We also propose a comprehensive training plan built around perceived needs, including one-on-one training with three mentors and several consultants and contributors, formal courses, practical laboratory rotations, seminars and meetings. The medical center at UCSF is known for its collaborative research spirit and its many training programs and fellowships geared toward promoting research and the individual growth of young investigators. UCSF is one of the top two schools in the amount of NIH research funding received and is known for its strong commitment to mentoring of young researchers. Cancer relevance: This project will improve our understanding of the effects of low doses of ionizing radiation on development of leukemia and address a number of remaining gaps in knowledge with respect to radiation- related carcinogenesis. The data will also allow a rare opportunity to explore the existence of carcinogenic effects of radiation exposure at low doses as well as to compare the quality and durability of various biological markers of radiation exposure. Study findings will help evaluate the risks of low-dose radiation exposure from diagnostic radiation procedures and address appropriateness of current public and occupational radiation safety limits which are primarily based on the studies of subjects exposed to high doses of ionizing radiation.

描述（由申请人提供）：背景：大量美国人口通过职业暴露或背景辐射接触小剂量辐射。额外的辐射暴露来自最近使用诊断放射学检查的增加，如x射线和计算机断层扫描。公众对暴露在辐射下的短期和长期健康影响的关注，特别是白血病，这一最易受辐射诱发的癌症之一，由于建议建造新的核电站和辐射废物处理场而进一步加剧。虽然高剂量和中等剂量的电离辐射对白血病的影响已在许多研究中得到证实，但较低剂量的影响尚不清楚。为了开展这方面的研究并发展我的科学事业，我需要在四个目标领域进行额外的培训和指导，包括流行病学研究的设计和实施、遗传和分子流行病学的研究方法、分析辐射相关风险和基因-环境相互作用的高级统计培训、以及科学研究伦理行为、论文写作和拨款准备方面的一般培训。目的：研究低剂量电离辐射暴露与白血病风险之间的关系，并从新的多学科角度评估环境和遗传因素在癌变中的作用。总的科学目标是扩大现有的与辐射有关的白血病风险研究机构，公共卫生目标是量化这种风险，对其进行解释，以便制定辐射安全限制，向受辐射者和一般公众通报情况，并制定预防战略。我的个人目标是利用UCSF流行病学与生物统计系、人类遗传学研究所和海伦·迪勒家庭综合癌症中心的资源，以及我的优秀导师团队，成为一名辐射癌症流行病学的独立研究员。我的长期目标是整合流行病学方法、统计建模和分子流行病学知识，以寻找辐射暴露的易感因素。研究和培训计划：在三项拟议研究中的第一项（辐射生物标志物研究）中，我们建议使用各种细胞遗传学测试来分析以前从切尔诺贝利清理工人收集的口腔细胞，以了解辐射暴露的持久影响。此外，我们将收集新的唾液样本，并通过RADRUE方法将辐射损伤与问卷中估计的剂量联系起来。在第二项研究（基因多态性研究）中，将通过对已知与电离辐射暴露和白血病风险增加相关的两种致癌基因（AML1和MLL）进行基因检测，获得有关辐射暴露后白血病发生生物学机制的新信息。在风险分析研究中，来自切尔诺贝利清理工人白血病研究的数据将与来自加拿大透视队列研究的数据相结合，以估计白血病的辐射依赖性风险，并将其与高剂量研究预测的风险进行比较。我们还提出了围绕感知需求建立的综合培训计划，包括有三位导师和几位顾问和贡献者的一对一培训，正式课程，实践实验室轮岗，研讨会和会议。加州大学旧金山分校的医学中心以其合作研究精神和许多培训项目和奖学金而闻名，这些项目和奖学金旨在促进研究和年轻研究者的个人成长。UCSF是获得NIH研究经费最多的两所学校之一，并以其对年轻研究人员的指导而闻名。癌症相关性：该项目将提高我们对低剂量电离辐射对白血病发展的影响的理解，并解决与辐射相关的致癌作用方面的一些知识空白。这些数据还将提供一个难得的机会来探索低剂量辐射照射是否存在致癌效应，并比较各种辐射照射生物标志物的质量和持久性。研究结果将有助于评估诊断性辐射程序造成的低剂量辐射暴露的风险，并解决目前的公共和职业辐射安全限制的适当性问题，这些限制主要基于对暴露于高剂量电离辐射的受试者的研究。