Temporal modifiers of the radon-smoking interaction.

Data on lung cancer mortality in a cohort of 3,347 Colorado Plateau uranium miners was reanalyzed to investigate the role of time-related modifiers of the radon-smoking interaction. A nested case-control sample of the cohort was drawn, matching each of the 258 lung cancer deaths with 15 controls drawn at random from the subjects who were born in the same year and still alive at the time the case died. As reported earlier, the dose response was sublinear for both total radon and total smoking, and their joint effect was approximately multiplicative. We fitted linear multiplicative models to these data, transforming the radon and smoking variables to improve their fit, and then added variables testing various temporal modifying effects and interactions. The strongest modifiers of the main effects of each variable taken separately were latency and duration of exposure. The strongest modifier of the interaction effect was the timing of radon and smoking exposures: Exposure to radon followed by smoking produced a significantly more-than-multiplicative effect, whereas the reverse sequence produced a significantly less-than-multiplicative effect. These findings suggest that smoking may act as a promoter of radon-initiated cells.