IOWA AND MISSOURI RADON LUNG CANCER STUDIES

根据对地下矿工的研究推断出的风险估计预测，住宅氡子体暴露导致美国每年约有19,000人死于肺癌。以前的病例对照流行病学研究考察了住宅氡暴露与肺癌之间的关系，但缺乏验证这些风险估计的能力。氡暴露剂量评估不准确、代理应答者比例高、病理检查不充分以及居住氡浓度低导致了对暴露的错误分类，并限制了这些研究的解释。爱荷华州氡肺癌一期研究旨在克服许多这些限制。第一阶段研究采用了超前的氡剂量评估、独立的组织学审查，研究人群的特点是地理稳定、活病例百分比高、潜在的高氡暴露。第一阶段的研究表明，接触住宅氡气会增加患肺癌的风险。为了完善这些估计，我们现在建议进行II期研究，检查住宅氡产品（子代）暴露与肺癌发展之间的关系。由于氡子体向肺组织传递的是实际辐射剂量，而不是氡气本身，为了进一步减少照射误分类，氡剂量估计需要考虑到住宅氡子体的暴露情况。这需要测量空气中氡子体的实际浓度，并综合氡子体随时间的暴露情况。II期研究将通过使用一种新型的回顾性氡子代集成玻璃探测器，得出更准确的回顾性氡剂量估计。特定目的1在控制混杂因素后，检验暴露于住宅氡子体与患肺癌风险增加有关的假设。我们将对回顾性氡“玻璃”探测器进行现场校准和实验室验证，并通过纳入氡子体暴露而不是氡气暴露来分析风险估计。特定目标II将确定最能描述住宅氡子体暴露与肺癌风险之间关系的剂量反应曲线的形状是线性的还是非线性的。特定目标III将检查暴露于氡子代是否有助于腺癌以及其他肺癌组织学类型的发展。对于目标II和III，我们将对来自爱荷华州和密苏里州氡肺癌研究的受试者的回顾性氡子代“玻璃”探测器得出的暴露估计进行汇总分析。在爱荷华州和密苏里州这两个相似地理区域进行的两项大规模流行病学研究之间汇集数据，将使我们能够增加样本量和统计能力。

Risk estimates, extrapolated from studies of underground miners, predict that residential radon progeny exposure accounts for approximately 19,000 lung cancer deaths each year in the United States. Previous case-control epidemiologic studies, which examined the relationship between residential radon exposure and lung cancer, lacked the ability to verify these risk estimates. Inaccurate dose assessment of radon exposure, a high percentage of proxy respondents, inadequate pathologic review, and low residential radon concentrations led to exposure misclassification and limited the interpretation of these studies. The Iowa Radon Lung Cancer Phase I study was designed to overcome many of these limitations. The Phase I study utilized advanced radon dose assessments, independent histologic review, and a study population that was characterized by geographic stability, high percentage of live cases, and potential for high radon exposure. The Phase I study demonstrated that exposure to residential radon gas increases the risk of developing lung cancer. To refine these estimates, we now propose Phase II studies that examine the association between residential radon product (progeny) exposure and the development of lung cancer. Because radon progeny deliver the actual radiation dose to the lung tissues, rather than radon gas itself, in order to reduce further the exposure misclassification, radon dose estimates need to take into account exposure to residential radon progeny. This requires measuring actual airborne radon progeny concentrations and integrating the exposure to radon progeny over time. The Phase II study will derive more accurate retrospective radon dose estimates by using a novel retrospective radon progeny integrating glass-based detector. Specific Aim I examines the hypothesis that exposure to residential radon progeny is associated with increased risk of developing lung cancer, after controlling for confounders. We will perform field calibration and laboratory validation of the retrospective radon "glass" detectors, and analyze the risk estimates by incorporating exposures to radon progeny, rather than exposures to radon gas. Specific Aim II will determine whether the shape of the dose response curve that best describes the relationship between residential radon progeny exposure and lung cancer risk is linear or nonlinear. Specific Aim III will examine whether exposure to radon progeny contributes to the development of adenocarcinoma, as well as other lung cancer histologic types. For Aims II and III we will use pooled analyses of exposure estimates that are derived from retrospective radon progeny "glass" detectors for subjects from the Iowa and Missouri Radon Lung Cancer Studies. The pooling of data between two large-scale epidemiologic studies from a similar geographic area, Iowa and Missouri, will allow us to increase sample size and statistical power.