Little M P, Muirhead C R
National Radiological Protection Board, Didcot, Oxon, UK.
Int J Radiat Biol. 1998 Oct;74(4):471-80. doi: 10.1080/095530098141348.
To investigate the evidence for a threshold in the cancer dose-response curve.
Japanese atomic bomb survivor cancer mortality data, based on follow-up to 1990, was used, taking account of random errors in DS86 dose estimates.
For all solid cancers analysed together, there is a significant positive dose response (two-sided p<0.05) if all survivors who received <0.5 Sv are considered, but the significance vanishes if doses of <0.2 Sv are considered; the same is also true for leukaemia. For solid cancer mortality there is no indication of curvilinearity in the dose response: no statistically significant improvement in fit to a linear relative risk model is provided by addition of quadratic or threshold dose terms. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer mortality data, the best estimate of the threshold is < 0.00 Sv (95% CI <0.00-0.13). If a linear-quadratic-threshold model is used the best estimate of the threshold is < 0.00 Sv (95% CI < 0.00-0.15). For leukaemia mortality there is highly statistically significant upward curvature in the dose response. In particular, if a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukaemia data, the best estimate of the threshold is 0.16 Sv (95% CI 0.05-0.40) (two-sided p=0.001 for test of departure of threshold from 0). However, there is no evidence for a threshold effect (two-sided p = 0.16) when a quadratic term is included in the dose response: the best estimate of threshold in this case is 0.09Sv (95% CI <0.00-0.29). Moreover, addition of a quadratic term improves the fit of a linear-threshold model at borderline levels of statistical significance (two-sided p = 0.07). Therefore, the most parsimonious description of the leukaemia dose response is provided by a linear-quadratic function of dose.
There is no evidence of threshold-type departures from the linear-quadratic dose response either for solid tumours or for leukaemia in the Japanese atomic bomb survivor mortality data.
研究癌症剂量反应曲线中阈值存在的证据。
使用了基于对日本原子弹爆炸幸存者随访至1990年的癌症死亡率数据，并考虑了DS86剂量估计中的随机误差。
对于所有综合分析的实体癌，如果考虑所有接受剂量小于0.5 Sv的幸存者，则存在显著的正剂量反应（双侧p<0.05），但如果考虑剂量小于0.2 Sv的情况，这种显著性就消失了；白血病情况也是如此。对于实体癌死亡率，剂量反应中没有曲线线性的迹象：添加二次项或阈值剂量项并不能显著改善线性相对风险模型的拟合度。如果将具有阈值的相对风险模型（假设阈值以上剂量反应呈线性）应用于实体癌死亡率数据，阈值的最佳估计值小于0.00 Sv（95%置信区间<0.00 - 0.13）。如果使用线性 - 二次 - 阈值模型，阈值的最佳估计值小于0.00 Sv（95%置信区间<0.00 - 0.15）。对于白血病死亡率，剂量反应中存在高度统计学显著的向上弯曲。特别是，如果将具有阈值的相对风险模型（假设阈值以上剂量反应呈线性）应用于白血病数据，阈值的最佳估计值为0.16 Sv（95%置信区间0.05 - 0.40）（阈值偏离0的双侧检验p = 0.001）。然而，当剂量反应中包含二次项时，没有阈值效应的证据（双侧p = 0.16）：此时阈值的最佳估计值为0.09 Sv（95%置信区间<0.00 - 0.29）。此外，在统计学显著性的临界水平上，添加二次项改善了线性 - 阈值模型的拟合度（双侧p = 0.07）。因此，白血病剂量反应的最简约描述是剂量的线性 - 二次函数。
在日本原子弹爆炸幸存者死亡率数据中，无论是实体瘤还是白血病，均没有证据表明存在偏离线性 - 二次剂量反应的阈值类型。
