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The two-stage clonal expansion model in occupational cancer epidemiology: results from three cohort studies
  1. Ariana Zeka1,2,
  2. Rebecca Gore1,
  3. David Kriebel1
  1. 1Department of Work Environment, University of Massachusetts, Lowell, Massachusetts, USA
  2. 2Institute for the Environment, Brunel University, Uxbridge, UK
  1. Correspondence to Dr Ariana Zeka, Institute for the Environment, Brunel University, Halsbury 149, Uxbridge UB8 3PH, UK; ariana.zeka{at}


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.

  • Two-stage clonal expansion
  • tumour initiation
  • tumour promotion
  • asbestos
  • silica
  • metal working fluid
  • lung cancer
  • larynx cancer
  • epidemiology
  • public health
  • cancer

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  • Funding This work was supported by a grant from the US National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, R01-OH03575, and a grant from the Centers for Disease Control and Prevention/Association of Teachers of Preventive Medicine number TS 0699.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.