title: Diesel engine exhaust and lung cancer mortality: time-related factors in exposure and risk.
abstract: To develop a quantitative exposure-response relationship between concentrations and durations of inhaled diesel engine exhaust (DEE) and increases in lung cancer risks, we examined the role of temporal factors in modifying the estimated effects of exposure to DEE on lung cancer mortality and characterized risk by mine type in the Diesel Exhaust in Miners Study (DEMS) cohort, which followed 12,315 workers through December 1997. We analyzed the data using parametric functions based on concepts of multistage carcinogenesis to directly estimate the hazard functions associated with estimated exposure to a surrogate marker of DEE, respirable elemental carbon (REC). The REC-associated risk of lung cancer mortality in DEMS is driven by increased risk in only one of four mine types (limestone), with statistically significant heterogeneity by mine type and no significant exposure-response relationship after removal of the limestone mine workers. Temporal factors, such as duration of exposure, play an important role in determining the risk of lung cancer mortality following exposure to REC, and the relative risk declines after exposure to REC stops. There is evidence of effect modification of risk by attained age. The modifying impact of temporal factors and effect modification by age should be addressed in any quantitative risk assessment (QRA) of DEE. Until there is a better understanding of why the risk appears to be confined to a single mine type, data from DEMS cannot reliably be used for QRA.
authors: Exponent Inc.-Health Sciences Practice, 15375 SE 30th Place, Suite 250, Bellevue, WA, USA.
authors: Suresh H
authors: SH
authors: Moolgavkar
authors: Exponent, Inc. - Health Sciences Practice, 149 Commonwealth Drive, Menlo Park, CA, USA.|Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, HRP Redwood Building, Stanford, CA, USA.
authors: Ellen T
authors: ET
authors: Chang
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Georg
authors: G
authors: Luebeck
authors: Exponent, Inc. - Health Sciences Practice, 149 Commonwealth Drive, Menlo Park, CA, USA.
authors: Edmund C
authors: EC
authors: Lau
authors: Exponent, Inc. - Data and Statistical Sciences Practice, 149 Commonwealth Drive, Menlo Park, CA, USA.
authors: Heather N
authors: HN
authors: Watson
authors: Independent Consultant, 2220 S. Vienna, Ruston, LA 71270, USA.
authors: Kenny S
authors: KS
authors: Crump
authors: Institute for Translational Epidemiology and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
authors: Paolo
authors: P
authors: Boffetta
authors: Toxicology and Human Health Risk Analysis, 13701 Quaking Aspen Place NE, Albuquerque, NM, USA.
authors: Roger
authors: R
authors: McClellan
mesh_terms: D002273:Carcinogens / Q000633:toxicity; D004781:Environmental Exposure; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000401:mortality*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D001335:Vehicle Emissions
keywords: Diesel exhaust; lung cancer; multistage carcinogenesis parametric models; quantitative risk assessment