in homes on the basis of miner data corresponding to as low an exposure as possible, or to use a risk model that accounts for the diminution of an inverse exposure-rate effect with decreasing exposure.
The committee also reviewed other evidence relevant to the biologic basis of its risk assessment approach. For the combined effect of smoking and radon, animal studies provided conflicting evidence on synergism, and there is uncertainty as to the relevance of the animal experiments to the patterns of smoking by people. Early attempts to identify a molecular "signature" of prior alpha-particle damage through the identification of unusual point mutations in specific genes have not yet proven useful, although approaches based on specific chromosomal aberrations show some promise, and all the principal histologic types of lung-cancer can be associated with radon exposure. Available evidence, albeit limited, supports the likelihood that a typical human population would have a broad spectrum of susceptibility to alpha-particle-induced carcinogenesis.
For estimating the risk imposed by exposure to indoor radon, the committee chose an empirical approach based on analysis of data from radon-exposed miners. Other approaches that the committee considered but did not use included a "dosimetric" approach, and use of "biologically-motivated" risk models. A dosimetric approach, in which radon risks are estimated by applying risk estimates from A-bomb survivor studies to estimates of radiation doses delivered to the lung, was not pursued because of the major differences in the type of radiation and exposure patterns compared with radon-progeny exposure. A biologic-based approach to modeling with a description of the various processes leading to radon-induced cancer was not followed primarily because of the present incomplete state of knowledge of many of these processes.
The committee turned to the empirical analysis of epidemiologic data as the basis for developing its risk model. Two sources of information were available: data from the epidemiologic studies of underground miners and data from the case-control studies of indoor radon and lung-cancer in the general population. Both groups include ever-smokers and never-smokers. Although the case-control studies provide direct estimates of indoor radon risk, the estimates obtained from these studies are very imprecise, particularly if estimated for never-smokers or ever-smokers separately, because the excess lung-cancer risk is likely to be small. Other weaknesses of the case-control studies are errors in estimating exposure and the limited potential for studying modifying factors, particularly cigarette smoking. Nonetheless, the committee considered the findings of a meta-analysis of the 8 completed studies.
In developing its risk models, the committee started with the recently reported analyses by Lubin and colleagues of data from 11 studies of underground miners—uranium miners in Colorado, New Mexico, France, Australia, the Czech