A meta-analysis of the relation between cumulative exposure to asbestos and relative risk of lung cancer

Abstract

Objectives: To obtain summary measures of the relation between cumulative exposure to asbestos and relative risk of lung cancer from published studies of exposed cohorts, and to explore the sources of heterogeneity in the dose-response coefficient with data available in these publications. Methods: 15 cohorts in which the dose-response relation between cumulative exposure to asbestos and relative risk of lung cancer has been reported were identified. Linear dose-response models were applied, with intercepts either specific to the cohort or constrained by a random effects model; and with slopes specific to the cohort, constrained to be identical between cohorts (fixed effect), or constrained by a random effects model. Maximum likelihood techniques were used for the fitting procedures and to investigate sources of heterogeneity in the cohort specific dose-response relations. Results: Estimates of the study specific dose-response coefficient (k(l.i)) ranged from zero to 42 x 10-3 ml/fibre-year (ml/f-y). Under the fixed effect model, a maximum likelihood estimate of the summary measure of the coefficient (κ1) equal to 0.42 x 10-3 (95% confidence interval (95% CI) 0.22 to 0.69 x 10-3) ml/f-y was obtained. Under the random effects model, implemented because there was substantial heterogeneity in the estimates of k(l,i) and the zero dose intercepts (A(i)), a maximum likelihood estimate of κ1 equal to 2.6 x 103 (95% CI 0.65 to 7.4 x 10-3) ml/f-y, and a maximum likelihood estimate of A equal to 1.36 (95% CI 1.05 to 1.76) were found. Industry category, dose measurements, tobacco habits, and standardisation procedures were identified as sources of heterogeneity. Conclusions: The appropriate summary measure of the relation between cumulative exposure to asbestos and relative risk of lung cancer depends on the context in which the measure will be applied and the prior beliefs of those applying the measure. In most situations, the summary measure of effect obtained under the random effects model is recommended. Under this model, potency, κ1, is fourfold lower than that calculated by the United States Occupational Safety and Health Administration.