PROBLEMS IN ASSESSING THE RELATIVE PREDICTIVE VALUE OF INTERNAL MARKERS VERSUS EXTERNAL EXPOSURE IN CHRONIC DISEASE EPIDEMIOLOGY

Epidemiology traditionally has relied on measures of ''external'' expo sure in determining the association between exposure and disease. Rece ntly, there has been increasing reliance on internal markers reflectin g internal dose and/or early stages of disease. In the context of obse rvational studies of chronic disease in which there is a known exposur e-disease association, the question arises whether the external exposu re or the internal marker is a better predictor of eventual disease ou tcome. Here we describe some simple approaches to evaluate the relativ e predictive value of the internal marker (or biomarker, defined in th e most general sense) versus the exposure, as well as their limitation s. The problems of assessing the predictive value of internal markers for chronic disease are illustrated via two examples: (a) carcinogens, cytogenetic outcomes, and cancer; and (b) asbestos, asbestosis, and l ung cancer. We conclude that it is unlikely that observational epidemi ology will allow a full assessment of the predictive value of cytogene tic outcomes versus exposure for cancer in humans exposed to known car cinogens in the near future, although animal studies could provide imp ortant complementary information. For asbestos, data to date indicate that the presence or absence of asbestosis is a better predictor of lu ng cancer in an exposed population than is the level of exposure to as bestos itself. In general, the most useful markers for predicting chro nic disease are ones which persist over time.