A reanalysis of liver cancer incidence in Danish patients administered thorotrast using a two-mutation carcinogenesis model.
In recent years, a two-mutation carcinogenesis (TMC) model has been used to analyze epidemiological data and estimate the radiation risks at low doses for the organs affected. Here the TMC model was used to reanalyze the liver cancer incidence in the Danish population in general and in patients administered Thorotrast, and to estimate the radiation risks for the liver. The data for 807 patients for whom sufficient data on the injected volumes of Thorotrast were available were used in this reanalysis. These data were combined with data on liver cancer incidence in the Danish population as the baseline or background incidence. Because males and females show different baseline liver cancer incidences, separate fits were made for males and females. The fits showed that the radiation effect could be ascribed entirely to the radiation dependence of the first mutation rate of the TMC model, which was higher for females than for males. The second mutation rate was not significantly dependent on dose. The radiation risks for the liver were calculated on the basis of the model parameters. These risks for lifetime exposures are about the same for males and females and are between a factor of 2 and 10 higher than current estimates. The discrepancy between the model results and previous risk estimates probably arises because the model calculations give more complete lifetime radiation risk estimates. For short-term exposures of the liver to ionizing radiation, the maximum radiation-induced excess liver cancer risk per unit dose applies to exposures at the age of about 10; exposures at ages above 35 have a radiation effect of less than approximately 15% of this maximum.
Leenhouts
H P
HP
RIVM, Bilthoven, The Netherlands. henk.leenhouts@rivm.nl
Brugmans
M J P
MJ
Andersson
M
M
Storm
H H
HH
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002273:Carcinogens / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D016013:Likelihood Functions; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012727:Sex Characteristics; D013911:Thorium Dioxide / Q000009:adverse effects*; D013997:Time Factors
D002273:Carcinogens; D013911:Thorium Dioxide