Temporal factors related to diesel exhaust exposure and lung cancer mortality in the Diesel Exhaust in Miners Study II nested case-control study

Abstract

BACKGROUND AND AIM: The Diesel Exhaust in Miners Study (DEMS) was an important contributor to the IARC re-classification of diesel exhaust as Group I carcinogen. We extended DEMS cohort follow-up by 18 years and the nested case-control study to include all newly identified lung cancer deaths and matched controls (DEMS II). Our purpose was to further characterize the exposure-response relationship with a focus on the effects of timing of exposure and exposure cessation. METHODS: We conducted a case-control study of lung cancer nested in a cohort of workers in eight nonmetal mines (376 lung cancer deaths, 796 controls). Controls were selected from workers who were alive when the case died, individually matched on mine, sex, race/ethnicity, and birth year (within 5 years). Based on an extensive historical exposure assessment, we estimated respirable elemental carbon (REC), an index of diesel exposure, for each cohort member. Odds ratios (ORs) were estimated by conditional regression analyses controlling for smoking and other confounders. RESULTS: ORs increased with increasing 15-year lagged cumulative exposure, peaking with a tripling of risk for exposures of about 950 to <1700 μg/m3-y (OR = 3.23; 95% CI = 1.47 to 7.10), followed by a plateau/decline among the heavily exposed (OR = 1.85; 95% CI = 0.85 to 4.04). Patterns of risk by cumulative REC exposure varied across four exposure time windows (Phomogeneity<0.001), with ORs increasing for exposures accrued primarily 10-19 years prior to death (Ptrend<0.001). Results provided little support for a waning of risk among workers whose exposures ceased for ≥20 years. CONCLUSIONS: DEMS II preliminary findings provide insight into the exposure-response relationship between diesel exhaust and lung cancer mortality and the effects of timing of exposure, with important implications for the assessment of risk from diesel exhaust by regulatory agencies. KEYWORDS: Diesel exhaust, lung cancer, occupational exposure