Lung cancer in chrysotile asbestos workers: analyses based on the two-stage clonal expansion model

To evaluate the magnitude and temporal pattern of lung cancer risk following exposure to chrysotile asbestos. I analyzed data on lung cancer mortality in a cohort of asbestos textile workers who were exposed to almost pure chrysotile. Employment history and industrial hygiene data were used to derive asbestos exposure estimates. These data were analyzed within the framework of the two-stage clonal expansion (TSCE) model and the Cox proportional hazards model. Under the TSCE model, the association between chrysotile asbestos and lung cancer mortality was primarily due to an exposure-induced increase in the proliferation of initiated cells. In a setting of protracted exposure to chrysotile asbestos, this model implies that the estimated hazard ratio was at its maximum between ages 40 and 65 years. Cox regression analyses support these conclusions; the estimated excess relative risk per fiber-year/ml was 0.053 (95% CI: 0.023, 0.124) at ages < 65 years, while there was minimal evidence of association at older attained ages. The TSCE model fits these data well, accommodating the observed departure from the proportional hazards assumption. These analyses suggest that the effect of chrysotile asbestos exposure on lung cancer risk varies with attained age.