Radon-induced lung cancer in French and Czech miner cohorts described with a two-mutation cancer model

Abstract

A two-mutation carcinogenesis model with clonal expansion of pre-malignant cells is used to describe lung cancer mortality data from studies on French and Czech miners with relatively low exposures to radon. The aim was to derive radon-induced lung cancer risk estimates applicable to different populations using a model description consistent with both cellular dose-response relationships, and previous model analyses of animal and human epidemiological data. The significantly different baseline lung cancer risks for the two cohorts that include the effects from the unknown smoking habits, are described with different background model parameters. A uniform description of the effect of radon for both miner cohorts is achieved by applying the same multiplicative effect for radon on the background mutation rates in the model. Incorporating the effects of decreased cellular proliferation at very advanced age improves the description of the baseline lung cancer risk, but does not lead to significant changes in the estimated radiation parameters. Here, a multi-stage model demonstrates the possibility of transferring radon-induced lung cancer risks across populations. The inherent age-time dose-rate relationships in the model allow for extrapolation to lifelong exposures to residential radon concentrations. The resulting cumulated (lifetime) risks from continuous exposure to low-level radon concentrations were found to agree with the results of the BEIR VI models.