China tin miners study and the Colorado Plateau uranium miners study, indicated that the lung-cancer risk associated with the combined exposure is greater than the sum of the risks associated with each factor individually, evidence of a synergistic effect between radon and tobacco smoke in the induction of lung-cancer. Data on tobacco use, available for 6 of 11 cohorts, are summarized in Table A-1. In the Colorado, Newfoundland and New Mexico studies, detailed data on tobacco use including duration, intensity, and cessation are available, whereas studies in China and Radium Hill identify individuals only as ever-smokers or never-smokers.

Since publication of the report by Lubin and others (1994a), studies of the Chinese tin miners, and of the Czech, Colorado, and French uranium miners have been updated or modified (Lubin and others 1997). Modifications of these four data sets are described in Table A-2. In addition, there has also been a reassessment of exposure for a nested case-control series within the Beaverlodge cohort of uranium miners, including all lung-cancer cases and matched control subjects (Howe and Stager 1996). For the Beaverlodge miners, exposure estimates were about 60% higher than the original values. Because of the computational and conceptual difficulties of merging case-control data with cohort data, only the data from the Beaverlodge cohort study with the original exposure estimates were used in the BEIR VI analysis.

In the first part of this appendix, we consider models for describing the relationship between exposure to radon and lung-cancer risk. We begin with a review of risk models developed by other investigators. In order to lay the foundation for the committee's risk model, we then discuss methods for combining data from different sources, including random-effects and two-stage methods. Those methods are then used in a combined reanalysis of the updated data from the 11 miner cohorts considered previously by Lubin and others (1994a).

By using a random-effects model, the overall effect of radon on lung-cancer risk can be described by fixed regression coefficients, and variation across cohorts characterized by random regression coefficients (Wang and others 1995). Two-stage regression analysis represents an alternative to random-effects methods, which benefits from an element of numerical simplicity. Although both methods are considered, the emphasis in the report is on the computationally simpler two-stage method.

In the second part of the appendix we focus on uncertainties in predictions of risk. There are many sources of uncertainty in health-risk assessments. Epidemiologic data on exposed human populations can be subject to considerable uncertainty. Retrospective exposure profiles are difficult to construct, particularly with chronic diseases such as cancer for which exposure data many years prior to disease ascertainment are needed. For example, radon measurements in homes taken today may not reflect past exposures because people change residences, make building renovations, or change their lifestyle such as sleeping with the bedroom window open or closed, and because of inherent variability in radon



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