Long-term Effects of Occupational Radiation Exposures

描述(由申请人提供)：美国核武器工作者的流行病学研究允许评估在数年或数十年的工作中累积的低剂量、低剂量率辐射暴露的影响。在这项拟议的研究中，我们将检查橡树岭国家实验室(ORNL)的一组受徽章监控的工作人员。这一具有重要流行病学意义的队列的最后一次死亡率跟踪调查是在18年前进行的，当时被认为是在1943年至1972年之间雇佣的工人。对这些数据的分析表明，职业性辐射剂量与所有癌症死亡率之间存在显著关联。我们建议将这一队列扩大到包括1943至1984年间雇用的工人，并更新至2007年的死亡率跟踪；根据寿命表预测，我们预计死亡人数是ORNL队列上次死亡跟踪中观察到的2.4倍。延长这一队列的随访不仅对统计能力很重要，而且因为辐射研究中的许多重要问题涉及辐射的长期影响，特别是对进展缓慢的恶性疾病，如非霍奇金淋巴瘤和慢性淋巴细胞白血病。拟议的分析将首先评估自暴露以来的时间，作为辐射影响的时间修正。除了使用曝光滞后和时间窗口分析的方法外，我们还将应用创新的方法来估计分布式滞后模型的核。先前对ORNL和其他队列的研究表明，暴露年龄是辐射与癌症联系的另一个重要因素。延长对这一队列的后续行动，并扩大花名册以包括更多最近聘用的人，将使我们能够更好地评估暴露年龄作为辐射影响的时间修饰物。除了暴露年龄效应的经验模型外，我们还将使基于生物学的多阶段癌症模型适用于这些数据。非放射性物质也可以改变电离辐射的影响。我们提出了两种评估非放射效应修饰物的方法：一种是考虑全队列；另一种是应用嵌套病例对照方法来评估辐射剂量与肺癌死亡率之间的关系。在全队列中，重点关注石棉、苯和铍的暴露，我们将根据ORNL提供的石棉和铍工人的历史名单以及NIOSH最近评估ORNL工人中苯的工作，制定这些危险的工作暴露矩阵。我们将应用创新的方法来检查这些非放射暴露的时间顺序是否会影响它们的联合影响。在肺癌死亡率的嵌套病例对照研究中，我们将利用医疗记录来评估吸烟的修饰或混杂，以及详细的工业卫生方法来评估石棉和铍的暴露潜力。这一USDOE队列的研究结果将根据美国能源部其他机构的研究结果进行评估；研究数据的汇编将有助于未来的汇集分析。通过这种方式，拟议的工作将大大加强关于USDOE队列中低水平辐射影响的现有流行病学信息。 与公共卫生的相关性：拟议的研究直接评估低剂量、低剂量率职业辐射暴露的长期影响，这是长期辩论的主题和明确的政策含义。这项工作的创新之处在于它质疑了关于淋巴癌没有辐射效应的既定范例。我们建议建立与时间相关的暴露效应的新模型，以考虑暴露时的潜伏期和年龄问题，应用基于生物学的致癌模型，并调查工作中的非放射性暴露，这将提高我们对暴露于DOE复合体中多种化学和物理制剂的后果的理解。

DESCRIPTION (provided by applicant): Epidemiological studies of US nuclear weapons workers allow evaluation of the effects of low dose, low dose rate radiation exposures accrued over years or decades of employment. In the proposed study, we will examine a cohort of badge-monitored workers at the Oak Ridge National Laboratory (ORNL). The last mortality follow-up of this epidemiologically important cohort was conducted 18 years ago and considered workers hired between 1943 and 1972. Analyses of these data revealed a significant association between occupational radiation dose and all cancer mortality. We propose to expand this cohort to include workers hired between 1943 and 1984 and update mortality follow-up through 2007; based on life table projections, we expect 2.4 times the number deaths observed in the last mortality follow-up of the ORNL cohort. Extending follow-up of this cohort is important not just for statistical power, but also because many important questions in radiation research concern the long term effects of irradiation, particularly on slow-progressing malignant diseases, such as non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The proposed analyses will commence with evaluation of time-since- exposure as a temporal modifier of radiation effects. In addition to using methods of exposure lagging and time-window analysis, we will apply innovative methods for kernel estimation of distributed lag models. Prior research on ORNL and other cohorts suggests that age-at-exposure is another important modifier of radiation- cancer associations. Extending follow-up of this cohort, and expanding the roster to include more recent hires, will allow us to better assess age-at-exposure as a temporal modifier of radiation effects. In addition to empirical models of age-at-exposure effects we will fit biologically-based multistage cancer models to these data. Non-radiological agents may also modify the effects of ionizing radiation. We propose two approaches to assessing non-radiological effect modifiers: one considering the full cohort; the other applying a nested case- control approach to assess modifiers of radiation dose- lung cancer mortality associations. In the full cohort, focusing on asbestos, benzene, and beryllium exposures, we will develop job-exposure-matrices for these hazards, informed by historical lists of asbestos and beryllium workers available at ORNL and recent work by NIOSH to assess benzene among ORNL workers. We will apply innovative methods to examine whether the temporal ordering of these non-radiological exposures impacts their joint effects. In the nested case-control study of lung cancer mortality, we will utilize medical records to assess modification or confounding by cigarette smoking as well as detailed industrial hygiene methods to assess asbestos and beryllium exposure potential. Study results for this USDOE cohort will be evaluated in relation to observations from studies of other DOE facilities; and, study data will be compiled in a manner that will facilitate future pooled analyses. In this way, the proposed work will substantially strengthen the available epidemiological information about low level radiation effects in USDOE cohorts. Public Health Relevance: The proposed study directly evaluates the long term effects of effects of low dose, low dose rate occupational radiation exposures, the subject of long debate and clear policy implications. This work is innovative in its questioning of an established paradigm regarding the absence of radiation effects on lymphatic cancers. We propose to novel models of time-related exposure effects to consider issues of latency and age at exposure, apply biologically-based carcinogenesis models, and investigate non-radiological exposures in work that will improve our understanding of the consequences of exposure to multiple chemical and physical agents in the DOE complex.