Latency analysis in epidemiologic studies of occupational exposures: Application to the Colorado plateau uranium miners cohort

Abstract

Background Latency effects are an important factor in assessing the public health implications of an occupational or environmental exposure. Usually, however, latency results as described in the literature are insufficient to answer public health related questions. Alternative approaches to the analysis of latency effects are warranted. Methods A general statistical framework for modeling latency effects is described. We then propose bilinear and exponential decay latency models for analyzing latency effects as they have parameters that address questions of public health interest. Methods are described for fitting these models to cohort or case‐control data; statistical inference is based on standard likelihood methods. Application A latency analysis of radon exposure and lung cancer in the Colorado Plateau uranium miners cohort was performed. We first analyzed the entire cohort and found that the relative risk associated with exposure increases for about 8.5 years and thereafter decreases until it reaches background levels after about 34 years. The hypothesis that the relative risk remains at its peak level is strongly rejected (P > 0.001). Next, we investigated the variation in the latency effects over subsets of the cohort based on attained age, level and rate of exposure, and smoking. Age was the only factor for which effect modification was demonstrated (P > 0.014). We found that the decline in effect is much steeper at older ages (60> years) than younger. Conclusion The proposed methods can provide much more information about the exposure–disease latency effects than those generally used. Am. J. Ind. Med. 35:246–256, 1999. © 1999 Wiley‐Liss, Inc.

Background stratified Poisson regression analysis of cohort data

“…To illustrate an extension of the proposed approach for background stratified Poisson regression analysis to an analysis in which a time-varying weight function is used to describe the modification of a cumulative dose–response association by time-since-exposure, we use data from a study of underground uranium miners (Hornung and Meinhardt 1987; Langholz et al 1999). The Colorado Plateau cohort that we examined includes 2,704 white men employed in underground uranium mining operations between 1 January 1950 and 31 December 1960.…”

“…One important example arises when modeling latency effects for a protracted exposure (Langholz et al 1999). The present approach permits fitting of these types of background stratified Poisson regression models.…”

“…Our approach avoids estimation of the stratum-specific parameters and therefore has no such constraints; this may be an advantage in analyses in which regression models are stratified on large numbers of multilevel study covariates, as in a pooled analysis of cohort data (Lubin et al 1995; Cardis et al 2007). Another limitation of the AMFIT program is the inability to easily fit models that parameterize latency functions for protracted exposures (Langholz et al 1999); the approach that is described here facilitates fitting of a wide range of Poisson regression models. Conveniently, this approach may be implemented using standard statistical software that provides the flexibility to specify general models, compute likelihood contributions, and maximize the likelihood function.…”

Objectivity and ethics in environmental health science.

“…In response, we noted that ionizing radiation can act as a promoter as well as an initiator of cancer (Doll 1978); that high doses can suppress immune function, which is associated with the appearance of secondary tumors within 2 years of radiotherapy (Appelbaum 1993); and that latencies of less than 5 years have been observed for miners exposed to radon (Hornung and Meinhardt 1987). A recent study of lung cancer among uranium miners found the best estimate of minimum latency to be less than 1 year (Langholz et al 1999).…”

Are Nested Case-Control Studies Biased?

“…13-15 Although radon exposure has been estimated for all miners in this cohort, we consider a hypothetical situation in which the only radon exposure-related information available on cohort members are the dates of start and end of mining.…”