Suchergebnisse

An exact formula for the tumor incidence rate in the usual two‐stage model of carcinogenesis is presented. This formula is simple and easily implemented on calculators and computers.

Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two‐stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth‐death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth‐death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic clones.

In the original article, we neglected to mention that this work was partly supported by the EU-ToxRisk project (An Integrated European "Flagship" Program Driving Mechanism-Based Toxicity Testing and Risk Assessment for the 21st Century) funded by the European Commission under the Horizon 2020 programme (Grant Agreement No. 681002). A correction has therefore been made to the Acknowledgments: "The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (IMIJU) under grant agreement number 115439, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. This work was supported by the 2015 CEFIC-LRI award (AL) and partly supported by the EU-ToxRisk project (An Integrated European "Flagship" Program Driving Mechanism-Based Toxicity Testing and Risk Assessment for the 21st Century) funded by the European Commission under the Horizon 2020 programme (Grant Agreement No. 681002). This publication reflects only the author's views and neither the IMI JU nor EFPIA nor the European Commission are liable for any use that may be made of the information contained therein." The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.