Lung cancer from radon: a two-stage model analysis of the WISMUT Cohort, 1955-1998.

A biologically based two-stage carcinogenesis model is applied to epidemiological data for lung cancer mortality in a large uranium miner cohort of the WISMUT company (Germany). To date, this is the largest uranium miner cohort analyzed by a mechanistic model, comprising 35,084 workers among whom 461 died from lung cancer in the follow-up period 1955-1998. It comprises only workers who were first employed between 1955 and 1989 and contains information on annual exposures to radon progeny. We fitted the model's free parameters, including the average growth time of one malignant cell into a lethal tumor. This lag time has an extraordinary value of 13 to 14 years, larger than that previously used or found in miner studies. Even though cohort-wide information on smoking habits is limited and the calendar-year dependence of tobacco smoke exposure was only implicitly accounted for by a birth cohort effect, we find good agreement between the modeled (expected) and empirical (observed) lung cancer mortality. Model calculations of excess relative lung cancer death risk agree well with those from the descriptive, BEIR VI-type exposure-age-concentration model for WISMUT miners. The large variety of exposure profiles in the cohort leads to a well-determined mechanistic model that in principle allows for an extrapolation from occupational to indoor radon exposure.