A METAANALYSIS OF THE RELATION BETWEEN CUMULATIVE EXPOSURE TO ASBESTOS AND RELATIVE RISK OF LUNG-CANCER

Objectives-To obtain summary measures of the relation between cumulati ve exposure to asbestos and relative risk of lung cancer from publishe d studies of exposed cohorts, and to explore the sources of heterogene ity in the dose-response coefficient with data available in these publ ications. Methods-15 cohorts in which the dose-response relation betwe en cumulative exposure to asbestos and relative risk of lung cancer ha s been reported were identified. Linear dose-response models were appl ied, with intercepts either specific to the cohort or constrained by a random effects model; and with slopes specific to the cohort, constra ined to be identical between cohorts (fixed effect), or constrained by a random effects model. Maximum likelihood techniques were used for t he fitting procedures and to investigate sources of heterogeneity in t he cohort specific dose-response relations. Results-Estimates of the s tudy specific dose-response coefficient (k(I.i)) ranged from zero to 4 2 x 10(-3) ml/fibre-year (ml/f-y). Under the fixed effect model, a max imum Likelihood estimate of the summary measure of the coefficient ((k ) over cap(1)$) equal to 0.42 x 10(-3) (95% confidence interval (95% C I) 0.22 to 0.69 x 10(-3)) ml/f-y was obtained. Under the random effect s model, implemented because there was substantial heterogeneity in th e estimates of k(I.i) and the zero dose intercepts (A(i)), a maximum l ikelihood estimate of (k) over cap(1)$ equal to 2.6 x 10(-3) (95% CI 0 .65 to 7.4 x 10(-3)) ml/f-y, and a maximum likelihood estimate of a eq ual to 1.36 (95% CI 1.05 to 1.76) were found. Industry category, dose measurements, tobacco habits, and standardisation procedures were iden tified as sources of heterogeneity. Conclusions-The appropriate summar y measure of the relation between cumulative exposure to asbestos and relative risk of lung cancer depends on the context in which the measu re 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, (k) o ver cap(1)$, is fourfold lower than that calculated by the United Stat es Occupational Safety and Health Administration.