A biologically based model for liver cancer risk in the Swedish thorotrast patients

Data on liver tumors among 416 Swedish patients who were exposed to Thorotrast between 1930 and 1950 were analyzed with the biologically based two-step clonal expansion (TSCE) model. For background data, the Swedish Cancer Register for the follow-up period 1958 to 1997 was used. Effects of radiation on the initiating mutation and on the clonal expansion rate explained the observed patterns well. The TSCE model permits the deduction of several kinetic parameters of the postulated tumorigenesis process. Dose rates of 5 mGy/year double the spontaneous initiation rate. The clonal expansion rate is doubled by 80 mGy/year, and for females it reaches a plateau at dose rates beyond 240 mGy/year. For males the plateau is not significant. The magnitude of the estimated promoting effect of radiation can be explained with a moderate increase in the cell replacement probability for the intermediate cells in the liver, which is strikingly similar to the situation in lung tumorigenesis.