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
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.