Risk of lung cancer associated with quantitative beryllium exposure metrics within an occupational cohort

Abstract

Objectives: Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological studies. The authors recently reported updated associations between lung cancer and beryllium exposure in a large, pooled occupational cohort. The authors conducted the present study to evaluate the shape of exposure-response associations between different exposure metrics and lung cancer in this cohort, considering potential confounders (race, plant, professional and short-term work status, and exposure to other lung carcinogens).

Methods: The authors conducted Cox proportional hazards regression analyses of lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA) exposure among 5436 workers, using age-based risk sets. Different exposure-response curves were fitted to the exposure metrics, including categorical, power, restricted cubic spline and piecewise log-linear fits.

Results: The authors found significant positive associations between lung cancer and mean (p < 0.0001) and maximum (p < 0.0001) exposure, adjusting for age, birth cohort and plant, and for cumulative (p = 0.0017) beryllium exposure, adjusting for these factors plus short-term work status and exposure to asbestos. The best-fitting models were generally categorical or piecewise log-linear, with the steepest increase in lung cancer risk between 0 and 10 μg/m(3) for both mean and maximum DWA exposure and between 0 and 200 μg/m(3)-days for cumulative DWA exposure. The estimated mean DWA beryllium exposure associated with 10(-3) excess lifetime risk based on the piecewise log-linear model is 0.033 μg/m(3).

Conclusion: This study provides evidence that lung cancer risk is elevated at levels near the current US Occupational Safety and Health Administration beryllium exposure limit of 2.0 μg/m(3) DWA for workers.