Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the chernobyl accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy-1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy-1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy-1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p= 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment

Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia

The thyroid dose due to 131I releases during the Chernobyl accident was reconstructed for children and adolescents in two cities and 2122 settlements in Belarus, and in one city and 607 settlements in the Bryansk district of the Russian Federation. In this area, which covers the two high contamination spots in the two countries following the accident, data on thyroid cancer incidence during the period 1991-1995 were analysed in the light of possible increased thyroid surveillance. Two methods of risk analysis were applied: Poisson regression with results for the single settlements and Monte Carlo (MC) calculations for results in larger areas or sub-populations. Best estimates of both methods agreed well. Poisson regression estimates of 95% confidence intervals (CIs) were considerably smaller than the MC results, which allow for extra-Poisson uncertainties due to reconstructed doses and the background thyroid cancer incidence. The excess absolute risk per unit thyroid dose (EARPD) for the birth cohort 1971-1985 by the MC analysis was 2.1 (95% CI 1.0-4.5) cases per 10(4) person-year Gy. The point estimate is lower by a factor of two than that observed in a pooled study of thyroid cancer risk after external exposures. The excess relative risk per unit thyroid dose was 23 (95% CI 8.6-82) Gy(-1). No significant differences between countries or cities and rural areas were found. In the lowest dose group of the settlements with an average thyroid dose of 0.05 Gy the risk was statistically significantly elevated. Dependencies of risks on age-at-exposure and on gender are consistent with findings after external exposures

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses \u3c5 \u3eGy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation

The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl.

Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology-specific genetic determinants in radiation-related PTC

Reconstruction of the Ingestion Doses Received by the Population Evacuated from the Settlements in the 30-KM Zone Around the Chernobyl Reactor.

As a consequence of the Chernobyl accident, about 50,000 people were evacuated from the settlements in the 30-km zone around the reactor in the period 3-11 d after the accident. As no countermeasures were implemented in the early phase, people continued to consume milk and some leafy vegetables. In this paper, average effective ingestion doses are modeled for evacuees. Input data for the assessment are the 137Cs activity per unit area, the ratios of the radionuclides relative to 137Cs, the mean day of evacuation, and intake rates for milk and green vegetables. The transfer of radionuclides from deposition to humans is estimated by modeling radionuclide interception by vegetation, weathering, and the time-dependent transfer of radionuclides to milk taking into account site-specific agricultural practices. Depending on the evacuation day and site, the estimated ingestion doses for the settlements are in the range of 20 to 1,300 mSv and 3 to 180 mSv for infants and adults, respectively. 131I is by far the most important isotope, the ingestion dose due to 133I is more than one order of magnitude lower. The most exposed organ is the thyroid, inducing more than 80% and 50% of the ingestion dose for infants and adults. The ingestion doses are compared to the doses due to inhalation and external exposure. The internal dose exceeds the external by a factor of about 2-10 for adults and 2-40 for 1-y-old infants depending on site and evacuation day. The thyroid doses assessed for the evacuees are consistent with results achieved in studies performed in areas outside the 30-km zone

A Consistent Radionuclide Vector after the Chernobyl Accident.

The radionuclide vector in the release plume from the destroyed unit 4 of the Chernobyl Nuclear Power Plant was assessed. Emphasis was laid on radionuclides relevant for the internal dose, including those with short half-lives, and on the radionuclide vector in the 30-km zone where practically no data in air or foodstuff are available. An evaluation of data was performed by comparing core analysis data and actual measurements of air filters and deposition data. The derived nuclide vector is consistent with most measurements and core analysis data. The ratios of the various radionuclides with regard to the guide isotope 137Cs vary both with direction of release and with increasing distance from the power plant. The variation and its causes are discussed, and a credible, consistent model for the vector at arbitrary distances from the nuclear power plant, in particular with regard to non-volatile radionuclides, is given. In that way the observed large discrepancies of the radionuclide vector determined by Russian and Ukrainian researchers, and those measured in Central and Northern European are explained by the fact that 90Sr, 95Zr, 140Ba, and 144Ce, which showed a much higher ratio to 137Cs close to the reactor than at 1,000 km distance, were attached to particle sizes of 8 µm and thus quicker deposited than the volatile radionuclides which were attached to 1 µm particulates on average. Also, the 131I to 137Cs ratio changes with distance by almost one order of magnitude which is explained by the higher deposition velocity of iodine

Reconstruction of the Inhalation Dose in the 30-KM Zone after the Chernobyl Accident.

Due to lack of measurements of activity concentrations in air, the assessment of the inhalation dose of the population evacuated from the 30-km zone after the Chernobyl accident is not possible from continuous filter measurements. Since the evaluation of the inhalation dose in each settlement of the zone is of great interest for epidemiological purposes, an approach was chosen that utilizes the available data on ground deposition of 137Cs, a recently performed best estimate of the radionuclide vector and its spatial distribution as well as the radionuclide dependent deposition velocity. The derived inhalation dose values in the 30-km zone range between 3 mSv to 150 mSv effective dose for adults depending on the distance to the reactor site and the day of evacuation. For 1-y-old infants the values range between 10 to 700 mSv. In Chernobyl town, an effective inhalation dose of 25 mSv until evacuation day was assessed. Thyroid doses due to inhalation ranged from 0.02 to 1 Sv for adults, for 1-y-old infants from 0.02 to 6 Sv. The inhalation dose in each settlement of the 30-km zone is approximately 8-13 times higher than the external exposure in each settlement if evacuation of the settlement occurred at an early stage. For settlements with evacuation at a later stage (day 10 or later) the inhalation dose was about 50-70% higher than the external dose. The dominant contribution to the effective inhalation dose comes from 131I (about 40%) and tellurium and rubidium isotopes (about 20-30%). Despite high zirconium and cerium ground depositions, zirconium and cerium isotopes contribute rather little to the inhalation dose which is mainly due to the great particle sizes to which they are attached. The relative contribution of short-lived radionuclides is, despite higher activities than at greater distances, less than 5%