Stochastic models for radiation carcinogenesis: tempora*

说明： 目前的辐射防护标准在很大程度上是基于原子弹幸存者的经验。然而，一个重要的问题是，日本战时暴露于瞬时辐射的人口中估计的风险，能否传播到当代西方人口，这些人通常在工作场所或其他地方暴露于长期辐射。当必须考虑与年龄和时间有关的辐射暴露因素时，就会出现额外的并发症。最近，一项使用传统流行病学方法对加拿大一大批职业暴露于低LET辐射的工人进行的分析得出了超额相对风险的估计，比根据原子弹幸存者的数据估计的高出一个数量级。这种矛盾能得到解决吗？这项研究建议继续开发基于多阶段致癌生物学原理的方法，以分析辐射致癌的流行病学数据。这些方法是对数据分析的传统流行病学方法的补充，可以以透明的方式纳入年龄和时间相关因素，包括延长暴露时间。这些方法已被我们和其他人用于分析职业队列数据，并产生了仅用传统方法难以获得的见解。例如，使用这些方法对上述加拿大队列中的肺癌发病率进行的分析表明，当适当考虑延长时间时，上述不一致现象就消失了。所开发的方法将应用于大量可用的数据集。具体地说，我们建议在加拿大国家剂量登记(CNDR)队列中分析低LET辐射与肺癌和结直肠癌发病率的关系，并延长随访至1999年。我们还建议在CNDR队列和由能源部建立的综合流行病学数据资源(CEDR)中的核工作人员队列中探索低LET辐射与肺癌死亡率之间的关系。这些分析的主要目的是探索各种与年龄和时间有关的因素以及延长暴露时间对辐射致癌风险的影响。

DESCRIPTION: Current radiation protection standards are based largely on the experience of the cohort of A-bomb survivors. An important question, however, is whether the risks estimated in a Japanese war-time population exposed to instantaneous radiation can be transported to contemporary western populations exposed typically to protracted radiation in the workplace or elsewhere. Additional complications arise when age- and time-related factors in radiation exposure must be considered. A recent analysis of a large Canadian cohort of workers occupationally exposed to low-LET radiation using conventional epidemiological methods yielded estimates of excess relative risk that were an order of magnitude higher than those estimated from the A-bomb survivor's data. Can such inconsistencies be resolved? This research proposes to continue the development of methods based on the biological principles of multistage carcinogenesis for analyses of epidemiological data on radiation carcinogenesis. These methods, which complement the traditional epidemiological approaches to data analyses, can incorporate age- and time-dependent factors, including protraction of exposure, in a transparent way. These methods have been used by us and others for analyses of occupational cohort data and have yielded insights that would have been difficult to obtain using traditional methods alone. As an example an analysis of lung cancer incidence in the Canadian cohort referred to above using these methods showed that the inconsistency referred to above disappears when protraction is properly accounted for. The developed methods will be applied to substantial available data sets. Specifically, we propose to analyze the association between low-LET radiation and incidence of lung and colorectal cancer in Canadian National Dose Registry (CNDR) cohort with extended follow-up through 1999. We also propose to explore the association between low-LET radiation and mortality from lung cancer in the CNDR cohort and the cohort of nuclear workers in the Comprehensive Epidemiological Data Resource (CEDR) set up by the Department of Energy. The main goals of these analyses are to explore the effects of various age- and time-related factors and of protraction of exposure on the risk of radiation carcinogenesis.