Evidence for curvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors
Evidence for curvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors
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DOI：
10.1080/095530096145364
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发表时间：
1996-07-01
影响因子：
2.6
通讯作者：
Muirhead, CR
中科院分区：
文献类型：
--
作者：
Little, MP;Muirhead, CR
最近公布的关于日本原子弹幸存者癌症发病率的数据使用了各种相对风险模型进行分析，这些模型考虑了剂量估计的误差，以评估低剂量下的剂量反应。综合分析所有实体癌，如果考虑所有接受0.5Sv的幸存者，则存在显著的正剂量反应(在单侧2.5%的显著水平上)，但如果考虑<；0.2Sv的剂量，则显著消失。如果将具有阈值的相对风险模型(假设剂量-反应线性高于阈值)拟合到实体癌数据，则大于约0.2Sv的阈值与数据不一致，而这些数据与没有阈值是一致的。线性-二次模型和具有指数杀菌项的线性-二次模型并不比线性模型提供更好的拟合。对于共同分析的三种主要辐射诱发白血病亚型(急性淋巴细胞性白血病、急性髓系白血病和慢性髓系白血病)，如果考虑所有接受0.5Sv的幸存者，则存在显著的正剂量反应(在单侧2.5%显著水平上)，但如果考虑<；0.2Sv剂量，其显著意义消失。如果将具有阈值的相对风险模型(假设剂量-反应线性高于阈值)拟合到白血病数据，则大于约0.3Sv的阈值与数据不一致。与实体癌症数据相比，白血病数据中对阈值水平的最佳估计与零显著不同，即使考虑到剂量-反应中可能的二次项，尽管处于统计学意义的边缘水平(p=0.04)。在0.2Sv以上的白血病剂量反应中几乎没有曲率性的证据。然而，由于分析中没有考虑到混淆和不确定性，可能低估了对剂量阈值估计的误差，再加上阈值缺乏生物学上的可信性，使得对这一结果的解释值得怀疑。
The recently released data on cancer incidence in the Japanese atomic bomb survivors are analysed using a variety of relative risk models which take account of errors in estimates of dose to assess the dose- response at low doses. For all solid cancers analysed together there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Linear-quadratic models and linear-quadratic models with an exponential cell-sterilization term provide no better fit than the linear model. For the three main radiation-inducible leukaemia subtypes analysed together (acute lymphatic leukaemia, acute myeloid leukaemia and chronic myeloid leukaemia) there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the leukaemia data, a threshold of more than about 0.3 Sv is inconsistent with the data. In contrast with the solid cancer data, the best estimate for the threshold level in the leukaemia data is significantly different from zero, even when allowance is made for a possible quadratic term in the dose-response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukaemia dose-response from 0.2 Sv upwards. However, the possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes the interpretation of this finding questionable.