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2016 marked the 30th anniversary of the Chernobyl Nuclear Power Plant accident. We and others wrote reviews for the 25th anniversary. Since then, additional papers have appeared and it seems timely to highlight lessons learned. To present, not a systematic review, but a commentary drawing attention to notable findings. We include not only recent reports and updates on previous results, but key findings from prior Chernobyl studies. The dose-dependent increase in Papillary Thyroid Cancer (PTC) following childhood I-131 exposure in Ukraine and Belarus has now been shown to persist for decades. Studies of post-Chernobyl PTCs have produced novel information on chromosomal rearrangements and gene fusions, critical to understanding molecular mechanisms. Studies of cleanup workers/liquidators suggest dose-related increases of thyroid cancer and hematological malignancies in adults. They also report increases in cardiovascular and cerebrovascular disease. If confirmed, these would have significant public health and radiation protection implications. The lens opacities following low to moderate doses found earlier are also a concern, particularly among interventional radiologists who may receive substantial lens doses. Finally, there is some, inconsistent, evidence for genetic effects among offspring of exposed persons. Further efforts, including improved dosimetry, collection of information on other risk factors, and continued followup/monitoring of established cohorts, could contribute importantly to further understand effects of low doses and dose-rates of radiation, particularly in young people, and ensure that appropriate public health and radiation protection systems are in place. This will require multinational collaborations and long-term funding.

Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. A nested case-control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986-2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = -0.47 (95% CI: < -0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

A large excess risk of thyroid cancer was observed among Belarusian/Russian/Baltic Chornobyl cleanup workers. A more recent study of Ukraine cleanup workers found more modest excess risks of thyroid cancer. Dose errors in this data are substantial, associated with model uncertainties and questionnaire response. Regression calibration is often used for dose-error adjustment, but may not adequately account for the full error distribution. We aimed to examine the impact of exposure-assessment uncertainties on thyroid cancer among Ukrainian cleanup workers using Monte Carlo maximum likelihood, and compare with results derived using regression calibration. Analyses assessed the sensitivity of results to various components of internal and external dose. Regression calibration yielded an excess odds ratio per Gy (EOR/Gy) of 0.437 (95% CI − 0.042, 1.577, p = 0.100), compared with the EOR/Gy using Monte Carlo maximum likelihood of 0.517 (95% CI − 0.039, 2.035, p = 0.093). Trend risk estimates for follicular morphology tumors exhibited much more extreme effects of full-likelihood adjustment, the EOR/Gy using regression calibration of 3.224 (95% CI − 0.082, 30.615, p = 0.068) becoming ~ 50% larger, 4.708 (95% CI − 0.075, 85.143, p = 0.066) when using Monte Carlo maximum likelihood. Results were sensitive to omission of external components of dose. In summary, use of Monte Carlo maximum likelihood adjustment for dose error led to increases in trend risks, particularly for follicular morphology thyroid cancers, where risks increased by ~ 50%, and were borderline significant. The unexpected finding for follicular tumors needs to be replicated in other exposed groups.

Although much is known about the radiation-related risk of thyroid cancer in those exposed at young ages, less is known about the risk due to adult exposure, particularly in men. We aimed to examine the association between thyroid radiation dose received during adulthood and thyroid cancer risk in men. We conducted a nested case–control study (149 cases; 458 controls) of male, Ukrainian cleanup workers who first worked in the Chornobyl zone between ages 18 and 59 years, with cases identified through linkage with the National Cancer Registry of Ukraine from 1988 to 2012. Individual thyroid doses due to external and internal exposure during the cleanup mission and during residence in contaminated settlements were estimated (total dose mean 199 mGy; range 0.15 mGy to 9.0 Gy). The excess odds ratio per gray (EOR/Gy) for overall thyroid cancer was 0.40 (95% CI:-0.05, 1.48; p-value = 0.118). Time since exposure was borderline significant (p-value = 0.061) in modifying this association so that less time since exposure was associated with a stronger EOR/Gy. An elevated, but nonsignificant association was observed for follicular thyroid cancer (EOR/Gy = 1.72; 95% CI:-0.25, 13.69; p-value = 0.155) based on a small number of cases (n = 24). Our findings for radiation-related overall thyroid cancer risk are consistent with evidence of increased risks observed in most of the other studies of adult exposure, though the magnitude of the effect in this study is lower than in the previous case–control study of Chornobyl cleanup workers.

Abstract This study revised the thyroid doses for 2582 Ukrainian in utero cohort members exposed to Chornobyl fallout (the Ukrainian in utero cohort) based on revision of: (i) 131I thyroid activity measured in the Ukrainian population, (ii) thyroid dosimetry system for entire Ukraine, and (iii) 131I ground deposition densities in Ukraine. Other major improvements included: (i) assessment of uncertainties in the thyroid doses considering shared and unshared error, and (ii) accounting for intake of short-lived radioisotopes of tellurium and iodine (132Te+132I and 133I). Intake of 131I was the major pathway for thyroid exposure, its median contribution to the thyroid dose was 97.4%. The mean prenatal and postnatal thyroid dose from 131I was 87 mGy (median = 17 mGy), higher than previous deterministic dose of 72 mGy (median = 12 mGy). For 39 individuals (1.5%) the dose exceeded 1.0 Gy, while the highest dose among the cohort members was 2.7 Gy. The geometric standard deviation (GSD) of 1000 individual stochastic doses varied from 1.9 to 5.2 with a mean of 3.1 and a median of 3.2. The lowest uncertainty (mean GSD = 2.3, median GSD = 2.2) was found for the subjects whose mothers were measured for 131I thyroid activity, while for individuals, whose mothers were not measured, the mean and median GSDs were 3.4. Uncertainties in thyroid doses were driven by shared errors associated with the parameters of the ecological model.

Thyroid dysfunction after exposure to low or moderate doses of radioactive iodine-131 (131I) at a young age is a public health concern. However, quantitative data are sparse concerning 131I-related risk of these common diseases. Our goal was to assess the prevalence of thyroid dysfunction in association with 131I exposure during childhood (≤ 18 years) due to fallout from the Chernobyl accident. We conducted a cross-sectional analysis of hypothyroidism, hyperthyroidism, autoimmune thyroiditis (AIT), serum concentrations of thyroid-stimulating hormone (TSH), and autoantibodies to thyroperoxidase (ATPO) in relation to measurement-based 131I dose estimates in a Belarusian cohort of 10,827 individuals screened for various thyroid diseases. Mean age at exposure (± SD) was 8.2 ± 5.0 years. Mean (median) estimated 131I thyroid dose was 0.54 (0.23) Gy (range, 0.001-26.6 Gy). We found significant positive associations of 131I dose with hypothyroidism (mainly subclinical and antibody-negative) and serum TSH concentration. The excess odds ratio per 1 Gy for hypothyroidism was 0.34 (95% CI: 0.15, 0.62) and varied significantly by age at exposure and at examination, presence of goiter, and urban/rural residency. We found no evidence of positive associations with antibody-positive hypothyroidism, hyperthyroidism, AIT, or elevated ATPO. The association between 131I dose and hypothyroidism in the Belarusian cohort is consistent with that previously reported for a Ukrainian cohort and strengthens evidence of the effect of environmental 131I exposure during childhood on hypothyroidism, but not other thyroid outcomes.

Background: There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations. Methods: This study included 115 PTCs diagnosed in a Ukrainian-American cohort ( n =13 243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression. Results: We identified a borderline significant linear-quadratic association ( P =0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements ( P =0.020) or tumours with BRAF or RAS point mutations ( P =0.008). Controlling for age, there were significant time trends in decreasing tumour size ( P <0.001), the extent of lymphatic/vascular invasion ( P =0.005), and overall invasiveness ( P =0.026). Conclusions: We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometries and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (– 1.0cm/Gy, P = 0.005) and chest circumference (–0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (–0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

Background While there is a robust literature on environmental exposure to iodine-131 ( 131 I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. Methods To assess the effect of 131 I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. Results The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume ( P  < 0.001). Heterogeneity of association was observed by attained age ( P  < 0.001) with statistically significant association remaining only in the subgroup of ≥18 years at screening ( P  < 0.001). For this group, increase in dose from 0.0005 to 0.15 Gy was associated with a 1.27 ml (95% CI: 0.46, 2.07) increase in thyroid volume. The estimated effect did not change with increasing doses above 0.15 Gy. Conclusions This is the first study to examine the association between 131 I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.