Long-term Effects of Occupational Radiation Exposures

描述（由申请人提供）：美国核武器工作人员的流行病学研究允许评估低剂量、低剂量率辐射暴露在数年或数十年工作中的影响。在提议的研究中，我们将检查一组在橡树岭国家实验室（ORNL）佩戴徽章的工作人员。这一具有流行病学重要性的队列的最后一次死亡率随访是在18年前进行的，研究对象是1943年至1972年间雇用的工人。对这些数据的分析显示，职业辐射剂量与所有癌症死亡率之间存在显著关联。我们建议扩大这一队列，纳入1943年至1984年期间雇用的工人，并更新至2007年的死亡率随访；根据生命表预测，我们预计在ORNL队列的最后一次死亡率随访中观察到的死亡人数是2.4倍。延长该队列的随访不仅对统计能力很重要，而且还因为辐射研究中的许多重要问题涉及辐射的长期影响，特别是对缓慢进展的恶性疾病，如非霍奇金淋巴瘤和慢性淋巴细胞白血病。拟议的分析将从评价照射后时间作为辐射效应的时间调节因子开始。除了使用暴露滞后和时间窗分析方法外，我们还将采用创新的方法对分布式滞后模型进行核估计。先前对ORNL和其他队列的研究表明，暴露年龄是辐射与癌症关联的另一个重要改变因素。扩大对这群人的跟踪调查，并将名单扩大到包括最近的雇员，将使我们能够更好地评估暴露年龄作为辐射效应的时间调节剂。除了年龄暴露效应的经验模型外，我们还将根据这些数据拟合基于生物学的多阶段癌症模型。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因子的方法：一种考虑整个队列；另一个应用嵌套病例对照方法来评估辐射剂量与肺癌死亡率的关系。在整个队列中，重点关注石棉、苯和铍的暴露，我们将根据ORNL现有石棉和铍工人的历史名单和NIOSH最近对ORNL工人中苯的评估工作，制定这些危害的工作暴露矩阵。我们将采用创新的方法来研究这些非放射性暴露的时间顺序是否会影响它们的联合效应。在肺癌死亡率的巢式病例对照研究中，我们将利用医疗记录来评估吸烟的改变或混淆，以及详细的工业卫生方法来评估石棉和铍的暴露潜力。美国能源部这一队列的研究结果将与美国能源部其他设施的研究观察结果进行评估；并且，研究数据将以一种便于将来汇总分析的方式进行汇编。通过这种方式，拟议的工作将大大加强美国能源部队列中关于低水平辐射效应的现有流行病学信息。

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.