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1712 Case study in data access and reanalysis: diesel engine exhaust and lung cancer mortality in the diesel exhaust in miners study (dems) cohort using alternative exposure estimates and radon adjustment

Introduction The Diesel Exhaust in Miners Study (DEMS), conducted by National Institute of Occupational Safety and Health (NIOSH) and National Cancer Institute (NCI), included 12 315 workers with 200 observed lung cancers from 8 U.S. non-metal mines (3 trona, 3 potash, 1 salt and 1 limestone). Retrospective cohort and case-control analyses by NIOSH and NCI scientists yielded a positive association between diesel exhaust exposure (DEE), represented by a respirable elemental carbon (REC) metric estimated retrospectively from carbon monoxide measurements, and lung cancer mortality. This finding was a major factor in the International Agency for Research on Cancer (IARC) classification of DEE as a human carcinogen. Methods Our team was given access to the DEMS data and conducted analyses to first replicate the original analyses and then conduct extended re-analyses. Our re-analyses focused on use of an alternative exposure metric developed using historical data on diesel equipment, engine horse power and ventilation rates without dependence on use of carbon monoxide as a surrogate for REC, inclusion of radon as a covariate in statistical models, and subgroup heterogeneity. Results We found associations with cumulative REC and average REC intensity using the alternative REC estimates were generally attenuated compared with those found using the original DEMS REC estimate. Most findings were statistically nonsignificant, especially after control for radon exposure, which substantially weakened associations with the original and alternative REC estimates. No significant findings were detected among all miners who worked exclusively underground. However, associations were anomalously strong among limestone miners; no association with REC or radon was found among workers at the other seven mines. Conclusions The large differences in results based on alternative exposure estimates, control for radon, and stratification by worker location or mine type highlight areas of uncertainty and the limited robustness of the DEMS data. These limitations must be considered in any extrapolation of the DEMS findings to other populations, and especially in using them for quantitative risk assessment. Moreover, the recently complete Advanced Collaborative Emissions Study (ACES) study sponsored by the Health Effects Institute and conducted at the Lovelace Respiratory Research Institute, Albuquerque, NM, indicated that chronic inhalation exposure of rats to low dilutions of exhaust from new technology diesel engines did not produce lung cancer. The results of both the DEMS and ACES findings will be reviewed to provide perspective for evaluating the cancer hazards of diesel-powered equipment, past, present and future.