Departments of Statistics.
Department of Preventive Medicine, College of Medicine, Keimyung University, Daegu, Korea.
Radiat Res. 2019 Aug;192(4):388-398. doi: 10.1667/RR15127.1. Epub 2019 Jul 29.
A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.
最近对原子弹幸存者寿命研究（日本广岛和长崎）中实体癌发病率的分析发现，男性而非女性的辐射剂量反应呈非线性、向上弯曲。需要进一步分析这一新的、出乎意料的发现。我们使用两种方法来研究这一发现。一种方法是将个体癌症部位或癌症部位组从所有实体癌中排除。另一种方法是使用联合分析，允许具有不同背景率趋势的癌症组中的背景率参数存在异质性。排除少数几个部位会导致男性在剩余的实体癌集合中弯曲消失；这些有影响力的部位中的一些在其背景特定年龄的发病率方面具有独特的特征，这些特征无法通过拟合所有实体癌的背景率模型来捕捉。排除少数几个部位也会导致女性出现弯曲。背景率的错误指定会导致对剂量反应形状的推断产生偏差，因此背景率的异质性可能至少部分解释了男性和女性在所有实体癌弯曲方面的剂量反应差异。我们得出结论，基于所有实体癌作为单一结果的分析不是评估寿命研究中实体癌辐射风险的最佳方法；通过允许跨部位的背景率异质性，同时比分析单个部位提供更大的评估辐射风险的能力，与合适的癌症组进行联合分析可能更为可取。
