been based on epidemiologic studies, primarily of the risk of lung-cancer among nonsmoking women married to current smokers, and on supporting biological evidence including the extensive data base on active smoking.

Combined Effect of Smoking and Radon as a Continued Source of Controversy in Risk Assessment

Because of this predominant role of cigarette-smoking as a cause of lung-cancer, an understanding of the joint effect of smoking and radon exposure is needed for assessing the risks of radon exposure for the general population, which includes never-smokers, current smokers, and former smokers. Incomplete understanding of the combined effect of these two carcinogens remains a key uncertainty in assessing the risk of indoor radon, and the consequences of synergism between radon and smoking in making quantitative risk estimates have not been universally appreciated. The underground miners who were participants in the epidemiologic studies that are the basis for currently used risk estimates were primarily smokers, and epidemiologic data from the miners' studies have not provided a precise characterization of the lung-cancer risk arising from radon exposure in never-smokers. However, active cigarette smokers are now a minority in the adult population of the United States (USDHHS 1989) and risk estimates are needed for both smokers and never-smokers.

This chapter addresses the joint effect of smoking and radon. It begins by describing trends of lung-cancer occurrence during the century and the implications of these trends for evaluating the role of indoor radon as a carcinogen. The chapter subsequently considers the numbers of cases of lung-cancer in smokers and never-smokers as risk projections have been made separately for these two groups. It then summarizes the evidence on the combined effect of smoking and radon, drawing on in vitro systems, animal exposures, and epidemiologic studies of miners and the general population. The BEIR IV Report (NRC 1988) also reviewed the evidence on the joint effect of smoking and radon in an appendix chapter. We begin with the conceptual basis for considering the combined effect of smoking and radon.

Concepts of Combined Effects

The 1985 Report of the U.S. Surgeon General (USDHHS 1985) set out a broad conceptual framework for considering the joint effect of cigarette-smoking with an occupational agent. The levels of potential interaction between the two agents are broad, ranging from molecular to behavioral (Table C-1). Some of the points of interaction would impact exposure, others—the exposure-dose relation, and others—the dose-response relation of radon progeny with lung-cancer risk. The epidemiologic data do not provide evidence relevant to assessing each of these potential points of intersection of radon-progeny exposure with cigarette-

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