title: Modeling Lung Carcinogenesis in Radon-Exposed Miner Cohorts: Accounting for Missing Information on Smoking.
abstract: Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a case-control study onto an entire cohort by means of a Monte Carlo resampling technique. As a proof of principle, this method is tested on a subcohort of 35,084 former uranium miners employed at the WISMUT company (Germany), with 461 lung cancer deaths in the follow-up period 1955-1998. After applying the proposed imputation technique, a biologically-based carcinogenesis model is employed to analyze the cohort's lung cancer mortality data. A sensitivity analysis based on a set of 200 independent projections with subsequent model analyses yields narrow distributions of the free model parameters, indicating that parameter values are relatively stable and independent of individual projections. This technique thus offers a possibility to account for unknown smoking habits, enabling us to unravel risks related to radon, to smoking, and to the combination of both.
authors.affiliation: Centre for Environmental Safety and Security, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: van Dillen
authors.affiliation: Centre for Environmental Safety and Security, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Fieke
authors.initials: F
authors.lastname: Dekkers
authors.affiliation: Centre for Environmental Safety and Security, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Medical Technology Research Group, Inholland University of Applied Sciences, Haarlem, The Netherlands.
authors.forename: Harmen
authors.initials: H
authors.lastname: Bijwaard
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Brüske
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.affiliation: Department of Radiation Protection and Health, Federal Office for Radiation Protection, Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kreuzer
authors.affiliation: Department of Radiation Protection and Health, Federal Office for Radiation Protection, Neuherberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Grosche
mesh_terms: D063646:Carcinogenesis; D016022:Case-Control Studies; D015331:Cohort Studies; D005858:Germany; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology*; D008906:Mining; D009010:Monte Carlo Method; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D009784:Occupational Diseases / Q000453:epidemiology; D016273:Occupational Exposure / Q000009:adverse effects*; D011886:Radon / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D011886:Radon
keywords: Lung cancer; Monte Carlo; WISMUT cohort; modeling; projection; radon; risk; smoking; uranium miners