Evaluation of Tritium: Relative Biological Effectiveness and Cancer Mortality

描述(申请人提供)：X射线和伽马辐射是公认的致癌物，流行病学研究表明它们对人类具有致癌性。相比之下，关于贝塔辐射对人类健康影响的流行病学研究很少。人们对长期接触贝塔排放物的影响更是知之甚少，比如氚，这是一种通过核燃料生产产生的氢的低能放射性同位素。辐射防护标准将贝塔辐射体的相对生物有效性(RBE)定为1，而伽马辐射体的相对生物有效性(RBE)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。这项拟议研究的目的有两个。首先，我们建议根据现有文献中的数据来估算氚的相对标准偏差。最终目标是应用准确的氚RBE来检查萨凡纳河核电站(SRS)一群核生产工人长期、低剂量氚暴露与癌症之间的关系，SRS是美国唯一的大型氚生产设施。其次，我们建议利用关于氚的相对生物效应的信息来重新评估与SRS设施中的氚相结合的其他形式的辐射暴露所导致的癌症死亡率。统计了1951年至1999年期间受雇的18883名工人的工人信息，包括每年的氚和伽马辐射剂量。利用这一数据，我们建议以伽马作为辐射的参考形式，建立氚的RBE分布。认识到由于氚剂量低，对SRS工作人员的氚成分的剂量-反应函数的量化将非常不精确，我们将使用马尔可夫链蒙特卡罗估计，这项技术将使我们能够根据实验室研究的数据建立先验分布，并测试流行病学数据集--SRS队列数据--与该分布的匹配程度。最后，我们将使用这些估计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行业以外的环境中。其他职业组和普通人群也经历了长期、低剂量的辐射暴露。因此，拟议的研究结果与广泛的职业和环境接触有关。 与公共卫生相关：与伽马辐射者相比，关于长期暴露于氚的影响及其相对生物有效性的流行病学证据很少。USDOE Savannah River工厂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与该队列中估计的氚剂量之间的关联。此外，我们将使用马尔可夫链蒙特卡罗方法将当前关于氚的RBE的信息与我们的流行病学数据结合起来，以估计氚的RBE的(后验)分布。

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.