Methods for testing interactions, with applications to occupational exposures, smoking, and lung cancer

Various approaches to assessing the interaction between smoking and occupational exposures are described. The definition of interaction depends on the measure of association under consideration and can be expressed in terms of disease risk, time, or dose. Simple descriptive methods and maximum likelihood model fitting methods are presented for analyzing interactions in terms of joint effects on disease risk. Methods for assessing the influence of exposures on times to disease, using appropriate denominators, are also described. The various approaches are illustrated with published data on lung cancer in relation to asbestos, radon daughters, chloromethyl ethers, and arsenic. Some of the mechanisms that can be invoked to explain the observed patterns include initiation and promotion, lung clearance, transport across cell membranes, and mucous secretion.