No abstract

Breast cancer risk from radiation exposure has been analyzed in the cohort of Japanese a-bomb survivors using empirical models and mechanistic two-step clonal expansion (TSCE) models with incidence data from 1958 to 1998. TSCE models rely on a phenomenological representation of cell transition processes on the path to cancer. They describe the data as good as empirical models and this fact has been exploited for risk assessment. Adequate models of both types have been selected with a statistical protocol based on parsimonious parameter deployment and their risk estimates have been combined using multi-model inference techniques. TSCE models relate the radiation risk to cell processes which are controlled by age-increasing rates of initiating mutations and by changes in hormone levels due to menopause. For exposure at young age, they predict an enhanced excess relative risk (ERR) whereas the preferred empirical model shows no dependence on age at exposure. At attained age 70, the multi-model median of the ERR at 1 Gy decreases moderately from 1.2 Gy(-1) (90% CI 0.72; 2.1) for exposure at age 25 to a 30% lower value for exposure at age 55. For cohort strata with few cases, where model predictions diverge, uncertainty intervals from multi-model inference are enhanced by up to a factor of 1.6 compared to the preferred empirical model. Multi-model inference provides a joint risk estimate from several plausible models rather than relying on a single model of choice. It produces more reliable point estimates and improves the characterization of uncertainties. The method is recommended for risk assessment in practical radiation protection.

Strong evidence for the statistical association between radiation exposure and disease has been produced for thyroid cancer by epidemiological studies after the Chernobyl accident. However, limitations of the epidemiological approach in order to explore health risks especially at low doses of radiation appear obvious. Statistical fluctuations due to small case numbers dominate the uncertainty of risk estimates. Molecular radiation markers have been searched extensively to separate radiation-induced cancer cases from sporadic cases. The overexpression of the CLIP2 gene is the most promising of these markers. It was found in the majority of papillary thyroid cancers (PTCs) from young patients included in the Chernobyl tissue bank. Motivated by the CLIP2 findings we propose a mechanistic model which describes PTC development as a sequence of rate-limiting events in two distinct paths of CLIP2-associated and multistage carcinogenesis. It integrates molecular measurements of the dichotomous CLIP2 marker from 141 patients into the epidemiological risk analysis for about 13 000 subjects from the Ukrainian-American cohort which were exposed below age 19 years and were put under enhanced medical surveillance since 1998. For the first time, a radiation risk has been estimated solely from marker measurements. Cross checking with epidemiological estimates and model validation suggests that CLIP2 is a marker of high precision. CLIP2 leaves an imprint in the epidemiological incidence data which is typical for a driver gene. With the mechanistic model, we explore the impact of radiation on the molecular landscape of PTC. The model constitutes a unique interface between molecular biology and radiation epidemiology.

Lung cancer mortality in the period of 1948-2002 has been analysed for 6,293 male workers of the Mayak Production Association, for whose information on smoking, annual external doses and annual lung doses due to plutonium exposures was available. Individual likelihoods were maximized for the two-stage clonal expansion (TSCE) model of carcinogenesis and for an empirical risk model. Possible detrimental and protective bystander effects on mutation and malignant transformation rates were taken into account in the TSCE model. Criteria for non-nested models were used to evaluate the quality of fit. Data were found to be incompatible with the model including a detrimental bystander effect. The model with a protective bystander effect did not improve the quality of fit over models without a bystander effect. The preferred TSCE model was sub-multiplicative in the risks due to smoking and internal radiation, and more than additive. Smoking contributed 57% to the lung cancer deaths, the interaction of smoking and radiation 27%, radiation 10%, and others cause 6%. An assessment of the relative biological effectiveness of plutonium was consistent with the ICRP recommended value of 20. At age 60 years, the excess relative risk (ERR) per lung dose was 0.20 (95% CI: 0.13; 0.40) Sv(-1), while the excess absolute risk (EAR) per lung dose was 3.2 (2.0; 6.2) per 10(4) PY Sv. With increasing age attained the ERR decreased and the EAR increased. In contrast to the atomic bomb survivors, a significant elevated lung cancer risk was also found for age attained younger than 55 years. For cumulative lung doses below 5 Sv, the excess risk depended linearly on dose. The excess relative risk was significantly lower in the TSCE model for ages attained younger than 55 than that in the empirical model. This reflects a model uncertainty in the results, which is not expressed by the standard statistical uncertainty bands.

The potential of thermoluminescence measurements of bricks from the contaminated area of the Techa river valley, Southern Urals, Russia, for reconstructing external exposures of affected population groups has been studied. Thermoluminescence dating of background samples was used to evaluate the age of old buildings available on the river banks. The anthropogenic gamma dose accrued in exposed samples is determined by subtracting the natural radiation background dose for the corresponding age from the accumulated dose measured by thermoluminescence. For a site in the upper Techa river region, where the levels of external exposures were extremely high, the depth-dose distribution in bricks and the dependence of accidental dose on the height of the sampling position were determined. For the same site, Monte Carlo simulations of radiation transport were performed for different source configurations corresponding to the situation before and after the construction of a reservoir on the river and evacuation of the population in 1956. A comparison of the results provides an understanding of the features of the measured depth-dose distributions and height dependencies in terms of the source configurations and shows that bricks from the higher sampling positions are likely to have accrued a larger fraction of anthropogenic dose from the time before the construction of the reservoir. The applicability of the thermoluminescent dosimetry method to environmental dose reconstruction in the middle Techa region, where the external exposure was relatively low, was also investigated.