Abstract
The biologically based two-stage clonal expansion (TSCE) model is used to analyze lung cancer in several miners studies, two new ones (Czech, French) and two historic ones (Chinese, Colorado). In all cases, the model assumptions are identical. An action of radiation on initiation, promotion, and transformation is allowed. While all four studies indicate a highly significant action of radiation on promotion, the action on initiation is not significant in the French cohort, and barely significant in the Colorado miners cohort. No action on transformation is found in the Colorado miners, while the other data sets indicate a borderline significance. The model can describe all the data sets adequately, with different model parameters. The observed patterns in exposure, time since beginning of exposure, birth year, age and calendar year are reproduced well. The doubling exposure rate for initiation is about 3.5 WLM/year in the new data sets, while it is higher in the historic data sets. For transformation the doubling rate is about 20 WLM/year for the new data sets, while again the historic data give higher estimates. The action of radiation on promotion is quite different in the four data sets. These differences also induce different risk estimates at low exposures. The larger power of the new studies at these low exposures, compared to the historic data requires less extrapolation when the risk at very low exposures is estimated.
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Notes
WLM (working level month): unit of exposure multiplying a concentration of radon decay products by the duration of exposure. An exposure of 1 WLM is defined as 170 h in an atmosphere of 1 WL where 1 WL is equivalent to any combination of radon decay products in 1 l of air that results in the emission of 130,000 MeV of energy of α-particles.
In terms of the spontaneous biological parameters \(q = \frac{1} {2}{\left( { - \gamma + {\sqrt {\gamma ^{2} + 4\alpha \mu } }} \right)}\) [19].
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Acknowledgements
The authors wish to thank J.C. Kaiser for useful discussions. This work was supported by the EU under contracts number FIGH-CT1999–0013 and FI6R-CT-2003–508842.
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Appendix
Appendix
Comparison of individual likelihood and Poisson regression
As was detailed above, in applications of the TSCE model it is customary to use an individual likelihood. The heuristic models favored for statistical analysis [7] can be more easily handled with Poisson regression. Simulations have shown that Poisson regression is not always ideal for estimating parameters in mechanistic models [30]. Therefore, a comparison of the two estimation procedures, individual likelihood and Poisson-likelihood, was performed using the French miners data. Two different software packages were used for estimating the parameters, MINUIT [22] for the individual likelihood and EPICURE (AMFIT sub-package) [31] for Poisson-regression. The resulting deviances are given in Table 9. It can be seen that the differences in deviance between the two models considered are very similar in the two statistical techniques. The estimated parameters and their estimated errors and confidence bounds agreed between the two techniques. Therefore we are confident that improvements in the deviance by refinements of the heuristic models (done with AMFIT) can be compared with improvements calculated with the individual likelihood.
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Heidenreich, W.F., Tomášek, L., Rogel, A. et al. Studies of radon-exposed miner cohorts using a biologically based model: comparison of current Czech and French data with historic data from China and Colorado. Radiat Environ Biophys 43, 247–256 (2004). https://doi.org/10.1007/s00411-004-0266-3
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DOI: https://doi.org/10.1007/s00411-004-0266-3