Modelling lung tumour risk in radon-exposed uranium miners using generalizations of the two-mutation model of Moolgavkar, Venzon and Knudson

Citation
Mp. Little et al., Modelling lung tumour risk in radon-exposed uranium miners using generalizations of the two-mutation model of Moolgavkar, Venzon and Knudson, INT J RAD B, 78(1), 2002, pp. 49-68
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
ISSN journal
0955-3002 → ACNP
Volume
78
Issue
1
Year of publication
2002
Pages
49 - 68
Database
ISI
SICI code
0955-3002(200201)78:1<49:MLTRIR>2.0.ZU;2-0
Abstract
Purposes: To model radon-induced lung cancer in uranium miners using a quas i-biological model of carcinogenesis. Materials and methods: Fitting of generalizations of the stochastic two-mut ation carcinogenesis model of Moolgavkar, Venzon and Knudson to a case-cont rol dataset nested within the cohort and to the full cohort of lung cancer mortality in the Colorado Plateau uranium miners, taking account of exposur e to cigarette smoke and to radon daughters. Results: Models with three mutations gave adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. T he overall fit of the two-mutation model to the case-control data was somew hat worse than that of the three-mutation model. For both the optimal two- and three-mutation models radon daughters and cigarette smoke were assumed to act on the first mutation rate. In the optimal two-mutation model, radon daughters also modified the intermediate cell death or differentiation rat e. In the optimal three-mutation model, radon daughters modified the second mutation rate. In all models, the action of radon daughters and cigarette smoke was markedly non-linear, particularly in their action on the mutation rates. The optimal two- and three-mutation models fitted to the cohort dat a were of slightly different form to those fitted to the case-control data. The model fits to the cohort data are preferred to those to the case-contr ol data on grounds of plausibility. Conclusions : Quasi-biological carcinogenesis models with three mutations g ive adequate descriptions of the time and age patterns of radon-daughter-in duced excess lung tumour mortality. The overall fit of the two-mutation mod el is somewhat worse than that of the three-mutation model.