Evaluation of Tritium: Relative Biological Effectiveness and Cancer Mortality

描述（由申请人提供）：x射线和伽马射线是公认的致癌物，从流行病学研究中得到了对人类致癌性的大量证据。相比之下，很少有关于-辐射对人类健康影响的流行病学研究。对于长期暴露于β排放物（如氚）的影响，人们了解得更少。氚是氢的一种低能放射性同位素，通过核燃料生产产生。辐射防护标准规定，与γ辐射者相比，β辐射者的相对生物有效性（RBE）为1。然而，最近的一项科学综述得出结论，氚的RBE需要重新评估。这项研究的目的是双重的。首先，我们提出基于现有文献的数据估计氚的RBE。最终目标是应用精确的氚RBE来检查在萨凡纳河厂址（SRS）的一群核生产工人中慢性低剂量氚暴露与癌症之间的关系，萨凡纳河厂址是美国唯一的大型氚生产设施。其次，我们建议利用有关氚的RBE的信息来重新评估与SRS设施中与氚相关的其他形式辐射暴露相关的癌症死亡率。工人信息，包括每年的氚和伽马辐射剂量，枚举了18883名工人从1951年至1999年雇用。利用这些数据，我们建议建立氚的RBE分布，以伽马作为我们的参考辐射形式。认识到由于氚剂量较低，对SRS工作人员氚成分的剂量反应函数的量化将非常不精确，我们将采用马尔可夫链蒙特卡罗估计，这种技术将使我们能够根据实验室研究数据建立先验分布，并测试流行病学数据集- SRS队列数据-与该分布的拟合程度。最后，我们将使用这些估计来提供更准确的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群也经历慢性低剂量辐射照射。因此，提出的研究结果与广泛的职业和环境暴露有关。

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.