Radon-induced lung cancer in smokers and non-smokers: risk implications using a two mutation carcinogenesis model

Three sets of data (population statistics in nonsmokers, data from an inves tigation of the smoking habits of British doctors and a study of Colorado u ranium miners) were used to analyse lung cancer in humans as a function of exposure to radon and smoking. One of the aims was to derive implications f or radon risk estimates. The data were analysed using a two-mutation radiat ion carcinogenesis model and a stepwise determination of the model paramete rs. The basic model parameters for lung cancer were derived from the age de pendence fit of the spontaneous lung cancer incidence in non-smokers. The e ffect of smoking was described by two additional parameters and, subsequent ly, the effect of radon by three other parameters; these five parameters de fine the dependence of the two mutation steps On smoking and exposure to ra don. Using this approach, a consistent fit and comprehensive description of the three sets of data have been achieved, and the parameters could, at le ast partly, be related to cellular radiobiological data. The model results explain the different effect of radon on non-smokers and smokers as seen in epidemiological data. Although the analysis was only applied to a limited number of populations, lung cancer incidence as a result of radon exposure is estimated to be about ten times higher fur people exposed at the age of about 15 than at about 50, although this effect is masked (especially for s mokers) by the high lung cancer incidence from smoking. Using the model to calculate the lung cancer risks from lifetime exposure to radon, as is the case for indoor radon, higher risks were estimated than previously derived from epidemiological studies of the miners' data. The excess absolute risk per unit exposure of radon is about 1.7 times higher for smokers of 30 ciga rettes per day than for non-smokers, even though, as a result of the low sp ontaneous tumour incidence in the non-smokers, the excess relative risk per unit exposure for the smokers is about 20 times lower than for the non-smo kers. This prediction could have serious consequences for the transfer of r isk estimates between populations. Although the solution of the model prese nted here is not unique but dependent on the model assumptions, the predict ions and risk implications are sufficiently supported to justify a thorough investigation of the applicability of the model to other radon data sets.