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The two-stage clonal expansion model in occupational cancer epidemiology: results from three cohort studies.

Zeka A; Gore R; Kriebel D
Occup Environ Med 2011 Aug; 68(8):618-624
Objectives: The objective of this work was to apply the two-stage clonal expansion model, with the intention to expand the literature on epidemiological applications of the model and demonstrate the feasibility of incorporating biologically based modelling methods into the widely used retrospective cohort study. Methods: The authors fitted the two-stage clonal expansion model model to three occupational cohort studies: (1) a cohort of textile workers exposed to asbestos and followed for lung cancer mortality; (2) a cohort of diatomaceous earth workers exposed to silica and also followed for lung cancer mortality; and (3) a cohort of automotive manufacturing workers exposed to straight metalworking fluid (MWF) and followed for larynx cancer incidence. The model allowed the authors to estimate exposure effects in three stages: cancer initiation (early effects), promotion or malignant transformation (late effects). Results: In the first cohort, the authors found strong evidence for an early effect of asbestos on lung cancer risk. Findings from analyses of the second cohort suggested early and less evidently late effects of silica on lung cancer risk. In the MWF (third) cohort, there was only weak evidence of straight MWF exposure effects on both early and late stages. The authors also observed a late birth cohort effect on larynx cancer risk. Conclusions: The findings for asbestos and silica were essentially confirmatory, supporting evidence for their early effects on lung cancer from a large body of literature. The effect of straight MWF on larynx cancer was less clear.
Analytical-processes; Automotive-industry; Biohazards; Biological-effects; Biological-monitoring; Biological-systems; Biostatistics; Cancer; Cancer-rates; Carcinogenesis; Carcinogenicity; Carcinogens; Epidemiology; Exposure-assessment; Exposure-levels; Exposure-methods; Larynx-cancer; Lung-cancer; Lung-disorders; Metal-compounds; Metal-fumes; Metal-industry-workers; Metal-workers; Metalworking; Metalworking-fluids; Metalworking-industry; Models; Mortality-data; Mortality-rates; Mortality-rates; Mortality-surveys; Occupational-diseases; Occupational-exposure; Occupational-hazards; Occupational-health; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis; Vapors; Work-areas; Work-environment; Worker-health; Work-operations; Work-organization; Work-performance; Workplace-studies
Dr Ariana Zeka, Institute for the Environment, Brunel University, Halsbury 149, Uxbridge UB8 3PH, UK
1332-21-4; 7631-86-9
Publication Date
Document Type
Journal Article
Email Address
Funding Type
Fiscal Year
Identifying No.
Grant-Number-R01-OH-003575; B09282011
Issue of Publication
Source Name
Occupational and Environmental Medicine
Performing Organization
University of Massachusetts Lowell
Page last reviewed: June 15, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division