Evaluation of Tritium: Relative Biological Effectiveness and Cancer Mortality

描述（由申请方提供）：X射线和伽马辐射是公认的致癌物，流行病学研究中有大量证据表明其对人类具有致癌性。相比之下，关于β辐射对人类健康影响的流行病学研究很少。人们对长期暴露于β-发射体（如氚，一种通过核燃料生产产生的氢的低能放射性同位素）的影响了解更少。辐射防护标准将β-发射体与γ-发射体的相对生物有效性（RBE）定为1。然而，最近的一项科学审查得出结论，氚的RBE需要重新评估。这项拟议研究的目标是双重的。首先，我们建议从现有的文献数据的基础上估计氚的RBE。最终目标是应用准确的氚RBE来检查在萨凡纳河站点（SRS）（美国唯一的大规模氚生产设施）的一组核生产工人中慢性低剂量氚暴露与癌症之间的关系。第二，我们建议利用有关氚的RBE的信息，重新评估癌症的死亡率与其他形式的辐射照射结合在SRS设施的氚。列举了1951-1999年雇用的18 883名工人的资料，包括氚和伽马辐射年剂量。利用这些数据，我们建议建立氚的RBE分布与γ作为我们的参考辐射形式。认识到，由于氚剂量的低幅度，SRS工作人员的氚成分的剂量反应函数的量化将是高度不精确的，我们将采用马尔可夫链蒙特卡罗估计，一种技术，使我们能够建立一个先验分布的基础上，从实验室研究的数据，并测试如何以及流行病学数据集-SRS队列数据-适合该分布。最后，我们将使用这些估计值来更准确地评估慢性低剂量辐射暴露与癌症结局之间的关系。辐射暴露存在于核燃料工业以外的环境中。其他职业群体和一般人口也受到长期低剂量辐射照射。因此，拟议研究的结果与广泛的职业和环境接触有关。 公共卫生相关性：关于长期接触氚的影响及其与伽马发射体相比的相对生物效应，几乎没有流行病学证据。美国能源部萨凡纳河厂址的独特之处在于，它参与了核武器用氚的生产。该项目的目标是评估癌症和估计的氚剂量之间的关联，在这个队列。此外，我们将使用马尔可夫链蒙特卡罗方法结合联合收割机目前的信息与我们的流行病学数据，以估计（后验）分布的氚RBE。

DESCRIPTION (provided by applicant): X-rays and gamma radiation are well-established carcinogens with substantial evidence of carcinogenicity in humans from epidemiological research. In contrast, there is very little epidemiological research on the human health effects of beta radiation. Even less is understood about the effects of chronic exposure to beta-emitters, such as tritium, a low- energy radioisotope of hydrogen that is produced through nuclear fuel production. Radiation protection standards assign a relative biological effectiveness (RBE) of 1 for beta-emitters compared to gamma-emitters. However, a recent scientific review concluded that the RBE of tritium needs reevaluation. The goal of this proposed study is twofold. First, we propose to estimate the RBE of tritium based on data from the existing literature. The ultimate goal is to apply an accurate RBE for tritium to examine the relationship between chronic, low-dose tritium exposure and cancer among a cohort of nuclear production workers at the Savannah River Site (SRS), the nation's only large- scale tritium production facility. Second, we propose to utilize the information regarding the RBE of tritium to reevaluate the cancer mortality associated with other forms of radiation exposure in conjunction with tritium at the SRS facility. Worker information, including annual tritium and gamma radiation dose, is enumerated for 18,883 workers employed from 1951-1999. Using this data, we propose to establish the distribution of the RBE of tritium with gamma as our reference form of radiation. Recognizing that quantification of a dose-response function for the tritium component of SRS workers will be highly imprecise due to the low magnitudes of tritium doses, we will employ Markov Chain Monte Carlo estimation, a technique that will allow us to establish an a priori distribution based on data from laboratory studies and to test how well an epidemiologic dataset - the SRS cohort data -- fits that distribution. Finally, we will use these estimates to provide more accurate evaluation of the relationship between chronic, low-dose radiation exposure and cancer outcomes. Radiation exposure exists in settings outside of the nuclear fuels industry. Other occupational groups, and the general population, also experience chronic, low-dose radiation exposures. Therefore, the results of the proposed research are relevant for a broad range of occupational and environmental exposures. PUBLIC HEALTH RELEVANCE: There is very little epidemiological evidence concerning the effects of protracted exposures to tritium and its relative biological effectiveness compared to gamma- emitters. The USDOE Savannah River Site is unique in that it was involved in tritium production for nuclear weapons. The goal of this project is to evaluate the association between cancer and estimated tritium dose in this cohort. In addition, we will use Markov Chain Monte Carlo methods to combine current information on the RBE for tritium with our epidemiological data in order to estimate a (posterior) distribution of the RBE for tritium.