The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)–exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood 131I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose–dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.

In collaboration with the Ukrainian Research Center for Radiation Medicine, the U.S. National Cancer Institute initiated a cohort study of children and adolescents exposed to Chornobyl fallout in Ukraine to better understand the long-term health effects of exposure to radioactive iodines. All 13,204 cohort members were subjected to at least one direct thyroid measurement between 30 April and 30 June 1986 and resided at the time of the accident in the northern part of Kyiv, Zhytomyr, or Chernihiv Oblasts, which were the most contaminated territories of Ukraine as a result of radioactive fallout from the Chornobyl accident. Thyroid doses for the cohort members, which had been estimated following the first round of interviews, were re-evaluated following the second round of interviews. The revised thyroid doses range from 0.35 mGy to 42 Gy, with 95 percent of the doses between 1 mGy and 4.2 Gy, an arithmetic mean of 0.65 Gy, and a geometric mean of 0.19 Gy. These means are 70% of the previous estimates, mainly because of the use of country-specific thyroid masses. Many of the individual thyroid dose estimates show substantial differences because of the use of an improved questionnaire for the second round of interviews. Limitations of the current set of thyroid dose estimates are discussed. For the epidemiologic study, the most notable improvement is a revised assessment of the uncertainties, as shared and unshared uncertainties in the parameter values were considered in the calculation of the 1,000 stochastic estimates of thyroid dose for each cohort member. This procedure makes it possible to perform a more realistic risk analysis.

1. Gut microbiota play an important role in host health. Yet, the drivers and patterns of microbiota imbalance (dysbiosis) in wild animals remain largely unexplored. 2. One hypothesised outcome of stress on animal microbiomes is a destabilised microbial community that is characterised by an increase in inter-individual differences compared with microbiomes of healthy animals, which are expected to be (a) temporally stable and (b) relatively similar among individuals. This set of predictions for response of microbiomes to stressors is known as the Anna Karenina principle (AKP) for animal microbiomes. 3. We examine the AKP in a wild mammal inhabiting disturbed environments by conducting a capture-mark-recapture survey of bank voles Myodes glareolus in areas that contrast in levels of radionuclide contamination (Chernobyl, Ukraine). 4. Counter to key predictions of the AKP, bank voles that are not exposed to radionuclides harbour variable (increased inter-individual differences) and temporally dynamic gut microbiota communities, presumably tracking the natural spatiotemporal variation in resources. Conversely, bank voles exposed to radionuclides host more similar gut microbiota communities that are temporally stable, potentially due to a dysbiosis or selection (on host or bacteria) imposed by chronic radiation exposure. 5. The implication of these data is that environmental stress (radiation exposure) can constrain the natural spatial and temporal variation of wild animal gut microbiota.

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.

Radiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.

This paper describes methods for estimating thyroid doses to Ukrainian children who were subjects of an epidemiological study of prenatal exposure and presents the calculated doses. Participants were 2,582 mother-child pairs in which the mother had been pregnant at the time of the Chornobyl accident on April 26, 1986 or in the two-three months following when 131 I in fallout was still present. Among these, 1,494 were categorized as "exposed"; a comparison group of 1,088 was considered "relatively unexposed." Individual in utero thyroid dose estimates were found to range from less than 1 mGy to 3,200 mGy, with an arithmetic mean of 72 mGy. Thyroid doses varied primarily according to stage of pregnancy at the time of exposure and level of radioactive contamination at the location of residence. There was a marked difference between the dose distributions of the exposed and comparison groups, although nine children in the latter group had calculated doses in the range 100-200 mGy. For those children who were born after the accident and prior to the end of June 1986, postnatal thyroid doses were also estimated. About 7.7% (200) of the subjects received thyroid doses after birth that were at least 10% of their cumulative doses.

The Chernobyl Tissue Bank (CTB) is an organisation that collects and stores samples of tumoral thyroid tissue obtained from Ukrainian and Russian subjects who were treated surgically for a thyroid cancer and had been exposed to (131)I from the Chernobyl accident. By 2012, the CTB had collected specimens of thyroid tissue from 2267 residents of Ukraine for the purpose of radiation research. Arithmetic mean thyroid doses and uncertainties have been estimated for all but 24 subjects for whom residence at the time of exposure was not found. The subjects have been classified into six groups or sub-groups according to the type of dosimetry-related information that is available for each of them. Excluding the 325 subjects with negligible radiation exposure, the arithmetic mean of the thyroid dose over all subjects is estimated as 0.4 Gy, with individual values ranging from <1 mGy to 13 Gy. The uncertainties in the individual thyroid dose estimates, characterised by the geometric standard deviations of their probability distributions, range from 1.3 to 8.7, with an arithmetic mean of 3.2.

With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R) By means of Parametric Full Maximum Likelihood and Regression Calibration (under the assumption that the data set of true doses has lognormal distribution), Nonparametric Full Maximum Likelihood, Nonparametric Regression Calibration, and by properly tuned SIMEX method we study the influence of measurement errors in thyroid dose on the estimates of λ 0 and EAR. The simulation study is presented based on a real sample from the epidemiological studies. The doses were reconstructed in the framework of the Ukrainian-American project on the investigation of Post-Chernobyl thyroid cancers in Ukraine, and the underlying subpolulation was artificially enlarged in order to increase the statistical power. The true risk parameters were given by the values to earlier epidemiological studies, and then the binary response was simulated according to the dose-response model.-