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Biomedical subjects

M J P Brugmans

Publications and source records attributed to M J P Brugmans.

8 recordsLinked to original sources
PubMed2006

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

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.

Adolescent↗
PubMed2003

A contribution to the linear no-threshold discussion.

The paper approaches the linear no-threshold (LNT) hypothesis, currently used as the basis for recommendations in radiological protection, from the point of view of the radiation mechanism. All considerations of the validity of the LNT hypothesis based on experiment or epidemiology are dismissed because of the impossibility of deriving statistically significant data at very low doses. Instead, the LNT hypothesis is assessed from a consideration of the mechanism of radiation action. The DNA double-strand break is proposed to be the crucial radiation-induced molecular lesion. A trace is made using a series of correlations that link the DNA double-strand break to effects at the cellular level and these cellular effects are linked to the induction of cancer. Multistep modelling of carcinogenesis is used to take the link through to a consideration of radiation risk. It is concluded that, from the point of view of radiation mechanism, at very low doses the LNT hypothesis of radiation action is valid, that is, the risk function has a positive slope from zero dose.

Cell Death↗
PubMed2002

A consistent two-mutation model of bone cancer for two data sets of radium-injected beagles.

A two-mutation carcinogenesis model has been applied to model osteosarcoma incidence in two data sets of beagles injected with 226Ra. Taking age-specific retention into account, the following results have been obtained: (1) a consistent and well-fitting solution for all age and dose groups, (2) mutation rates that are linearly dependent on dose rate, with an exponential decrease for the second mutation at high dose rates, (3) a linear-quadratic dose-effect relationship, which indicates that care should be taken when extrapolating linearly, (4) highest cumulative incidences for injection at young adult age, and highest risks for injection doses of a few kBq kg(-1) at these ages, and (5) when scaled appropriately, the beagle model compares fairly well with a description for radium dial painters, suggesting that a consistent model description of bone cancer induction in beagles and humans may be possible.

Animals↗
PubMed2002

The implications of re-analysing radiation-induced leukaemia in atomic bomb survivors: risks for acute and chronic exposures are different.

Implications of risk estimates, as required for practical radiation protection purposes, were explored through a preliminary re-analysis of leukaemia in the Japanese atomic bomb survivors using a biologically based cancer model. The calculations for the risks posed for contracting leukaemia pointed to important differences between low-dose-rate ('chronic') and high-dose-rate ('acute') exposures. For example, the risks caused by long-term ('chronic') exposures are calculated to be substantially lower than those for 'acute' exposures. In view of these model predictions the results of epidemiological studies are discussed.

Aged↗
PubMed2002

Implications of the analysis of epidemiological data using a two-mutation carcinogenesis model for radiation risks.

A two-mutation carcinogenesis (TMC) model is used as a bridge between cellular radiation biological effects and the incidence of cancer. This model has been applied to several sets of experimental animal and epidemiological data. In this paper the advantage of the model and the implications for radiation risks at low doses are discussed with respect to the age and dose dependence of cancer incidence and the effect of age at exposure on radiation risk; the link between the radiation effect and background cancer incidence and the transfer of radiation risk across different population groups; the implications of acute and protracted radiation exposures for risks at low doses and the dose-effect relationship for radium induced bone cancer.

Age Factors↗
PubMed2002

Lower radiation weighting factor for radon indicated in mechanistic modelling of human lung cancer.

A two-mutation carcinogenesis (TMC) model was fitted to the age-dependent lung cancer incidence in a cohort of Dutch Hodgkin patients treated with radiotherapy. Employing the results of previous TMC analyses of lung cancer due to smoking (by British doctors) and due to exposure to radon (for Colorado miners) a model fit was obtained with an estimate for the low LET radiation effect at the cellular level. This allows risk calculations for lung cancer from low LET radiation. The excess absolute risks are in tune with the values reported in the literature, the excess relative risks differ among the exposed groups. Comparing the cellular radiation coefficients for radon and for low LET radiation leads to an estimated radiation weighting factor for radon of 3 (0.1-6).

Humans↗
PubMed2002

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.

Adolescent↗