Methodologic issues in using epidemiologic studies of occupational cohorts for cancer risk assessment

This paper focuses on presenting a review and discussion of the major methodologic issues involved in using epidemiologic studies of occupational groups for assessing human cancer risks. Although animal studies have been most often used for quantitative risk assessment, it is generally recognized that well conducted epidemiologic studies would provide the best basis for estimating human risk. However, there are several features related to the design and analysis of epidemiologic studies which frequently limit their usefulness for quantitating risks. The lack of accurate information on exposure in epidemiologic studies is perhaps the most frequently cited limitation of these studies for risk assessment. However, other features of epidemiologic study design such as statistical power, length of follow-up, selection bias, confounding and effect modification may also limit the inferences that can be drawn from these studies. Furthermore even when the aforementioned limitations are overcome, substantial uncertainty exists concerning the choice of an appropriate statistical (or biologic) model for extrapolation beyond the range of exposures observed in a particular study. An empirical example is provided in which estimates of risk varied by nearly 3 orders of magnitude depending on which functional form of the model was chosen. Modeling of epidemiologic data for QRA should be based upon internal comparisons rather than on modeling Standardized Mortality Ratios (SMRs) when possible. Because of the limitations discussed in this paper, epidemiologic data should not be viewed as a panacea for the problems inherent in using animal bioassay data for QRA.(ABSTRACT TRUNCATED AT 250 WORDS)