POTENTIAL PITFALL IN USING CUMULATIVE EXPOSURE IN EXPOSURE-RESPONSE RELATIONSHIPS - DEMONSTRATION AND DISCUSSION

Cumulative exposure is frequently used as a measure of exposure in the quantitative analysis of epidemiologic studies. It is recognized that the imposed symmetry between duration and intensity of exposure is a potential problem with this measure, but it is less widely recognized that the finding of an exposure-response relationship, using cumulativ e exposure as the exposure metric, does not necessarily imply that exp osures were accurately or even consistently estimated. This report des cribes a simulation study drawn from a nested case-control analysis of mesothelioma in a cohort of asbestos cement workers. Intensity of exp osure in the range of 0.1-40 fibers/ml was randomly assigned to subjec ts. Logistic regression analysis demonstrated that there was no associ ation between mesothelioma risk and the randomly assigned intensity of exposure. However, in 171 (86%) of 200 trials, mesothelioma risk was significantly associated with cumulative exposure, even though intensi ty of exposure remained randomly assigned. A strong exposure-response relationship might thus be misleading. One would be more confident abo ut quantitative risk assessment when there are a large number of indep endent studies available for analysis. (C) 1995 Wiley-Liss, Inc.