Little Mark P, Haylock R G E, Muirhead C R
Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Int J Radiat Biol. 2002 Jan;78(1):49-68. doi: 10.1080/09553000110085797.
To model radon-induced lung cancer in uranium miners using a quasi-biological model of carcinogenesis.
Fitting of generalizations of the stochastic two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson to a case-control dataset nested within the cohort and to the full cohort of lung cancer mortality in the Colorado Plateau uranium miners, taking account of exposure to cigarette smoke and to radon daughters.
Models with three mutations gave adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model to the case-control data was somewhat worse than that of the three-mutation model. For both the optimal two- and three-mutation models radon daughters and cigarette smoke were assumed to act on the first mutation rate. In the optimal two-mutation model, radon daughters also modified the intermediate cell death or differentiation rate. In the optimal three-mutation model, radon daughters modified the second mutation rate. In all models, the action of radon daughters and cigarette smoke was markedly non-linear, particularly in their action on the mutation rates. The optimal two- and three-mutation models fitted to the cohort data were of slightly different form to those fitted to the case-control data. The model fits to the cohort data are preferred to those to the case-control data on grounds of plausibility.
Quasi-biological carcinogenesis models with three mutations give adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model is somewhat worse than that of the three-mutation model.
使用一种准生物致癌模型对铀矿工人中氡诱发的肺癌进行建模。
将Moolgavkar、Venzon和Knudson的随机双突变致癌模型的推广形式，与嵌套在该队列中的病例对照数据集以及科罗拉多高原铀矿工人肺癌死亡率的完整队列进行拟合，同时考虑接触香烟烟雾和氡子体的情况。
具有三个突变的模型能够充分描述氡子体诱发的额外肺肿瘤死亡率的时间和年龄模式。双突变模型对病例对照数据的整体拟合略逊于三突变模型。对于最优的双突变和三突变模型，均假定氡子体和香烟烟雾作用于首次突变率。在最优双突变模型中，氡子体还改变了中间细胞的死亡或分化率。在最优三突变模型中，氡子体改变了第二次突变率。在所有模型中，氡子体和香烟烟雾的作用均呈明显的非线性，尤其是在它们对突变率的作用方面。拟合队列数据的最优双突变和三突变模型的形式与拟合病例对照数据的模型略有不同。基于合理性，队列数据的模型拟合优于病例对照数据的模型拟合。
具有三个突变的准生物致癌模型能够充分描述氡子体诱发的额外肺肿瘤死亡率的时间和年龄模式。双突变模型的整体拟合略逊于三突变模型。
