Journal Article

Analysis of epidemiological cohort data on smoking effects and lung cancer with a multi-stage cancer model

H. Schöllnberger, M. Manuguerra, H. Bijwaard, H. Boshuizen, H.P. Altenburg, S.M. Rispens, M.J.P. Brugmans and P. Vineis

in Carcinogenesis

Volume 27, issue 7, pages 1432-1444
Published in print July 2006 | ISSN: 0143-3334
Published online January 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi345
Analysis of epidemiological cohort data on smoking effects and lung cancer with a multi-stage cancer model

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A stochastic two-stage cancer model is used to analyse the relation between lung cancer and cigarette smoking. The model contains the main rate-limiting stages of carcinogenesis, which include initiation, promotion (clonal expansion of initiated cells), malignant transformation and a lag time for tumour formation. Various data sets were used to test the model. These include the data of a large prospective collaborative project carried out in 10 different European countries, the European Prospective Investigation into Cancer and Nutrition (EPIC). This new data set has not been modelled before. The model is also tested on other published data from CPS-II (Cancer Prevention Study II) of the American Cancer Society and the British doctors' study. The analyses indicate that the EPIC data are best described with smoking dependence on the rates of malignant transformation and clonal expansion. With increasing smoking rates, saturation effects in the two exposure rate-dependent model parameters were observed. The results find confirmation in the biological literature, where both mutational effects and promotional effects of cigarette smoke are documented.

Keywords: CI, confidence interval; CPS, Cancer Prevention Study; EPIC, European Prospective Investigation into Cancer and Nutrition; ERR, excess relative risk; LEAR, lifetime excess absolute risk; LERR, lifetime excess relative risk; TSCE, two-step clonal expansion model

Journal Article.  11366 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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