Dose Reconstruction for Epidemiological Studies among Ukrainian Chernobyl Cleanup Workers.

The present paper provides an overview of the methods and summarizes the results of estimating radiation doses and their uncertainties for Ukrainian-American epidemiological studies among the Chernobyl (Chornobyl) cleanup workers. After the Chernobyl accident occurred on April 26, 1986, more than 300,000 Ukrainian cleanup workers took part between 1986 and 1990 in decontamination and recovery activities at the site of the Chernobyl Nuclear Power Plant. The U.S. National Cancer Institute in collaboration with the Ukrainian National Research Center for Radiation Medicine conducted several epidemiological studies in this population. An important part of these studies was the reconstruction of the study participants' radiation doses and the assessment of uncertainties in doses. A method called realistic analytical dose reconstruction with uncertainty estimation (RADRUE) was used to calculate the doses from external irradiation during cleanup missions, which was the main exposure pathway for most study participants. At the initial phase of the accident during the atmospheric releases of radioactivity from the destroyed reactor, the cleanup workers also received doses from inhalation of radionuclides. In addition, study participants received doses at their places of residence, especially those who lived in highly contaminated areas. The radiation doses estimated for 2,048 male cleanup workers included in the Ukrainian-American epidemiological studies varied widely: (i) bone-marrow doses from external irradiation in the case-control study of leukemia of 1,000 cleanup workers ranged from 3.7 × 10-5 mGy to 3.3 Gy (mean = 92 mGy); (ii) thyroid doses in the case-control study of thyroid cancer in 607 persons from all exposure pathways combined were from 0.15 mGy to 9.0 Gy (mean = 199 mGy); (iii) gonadal doses in 183 cleanup workers from all exposure pathways combined in the study of germline mutations in the offspring after parental irradiation (trio study) ranged from 0.58 mGy to 4.1 Gy (mean = 392 mGy); (iv) thyroid doses in the human factor uncertainties study among 47 persons were from 20 mGy to 2.1 Gy (mean = 295 mGy); and (v) lung doses in the study of germline genetic variants associated with host susceptibility to COVID-19 estimated for 211 cleanup workers were from 0.024 mGy to 2.5 Gy (mean = 249 mGy). Doses of female cleanup workers were much lower than those of male cleanup workers: the mean doses for female cleanup workers were 27 mGy for 34 women included in the trio study and 56 mGy for 48 women participated in the study of germline genetic variants associated with host susceptibility to COVID-19. Uncertainties in dose estimates included two components: (i) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters; and (ii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, or missing responses during personal interviews with cleanup workers conducted long after exposure. This paper also discusses possible developments and improvements in the methods to assess the radiation doses and associated uncertainties for cleanup workers.

Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident.

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.

Prevalence of Thyroid Nodules in Residents of Ukraine Exposed as Children or Adolescents to Iodine-131 from the Chornobyl Accident.

Background: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). Methods: This is a cross-sectional study of radiation dose (mean = 0.53 gray, range: 0.0003-31 gray) and screen-detected thyroid nodules conducted in 1998-2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (excess odds ratio [EOR]/Gy) and confidence intervals (CIs) were estimated using logistic regression. Results: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose-response associations were found for all nodules and nodule groups with doses <5 Gy except individuals with non-neoplastic nodules. Among individuals with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; CI: 2.19-15.5) was significantly higher than for non-neoplastic nodules (0.24; CI: 0.07-0.74), but the EOR/Gy did not vary by nodule size or number. Conclusions: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12-14 years following exposure, and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose-response patterns by nodule characteristics and provide insights into thyroid nodule etiology.

Association between radiation dose, thyroid hormone, and IQ levels in children exposed to radiation in utero after the Chernobyl accident.

Few studies have explored the effects of n utero radiation exposure on human health and cognition and none have taken into account thyroid hormone levels (T3), which have shown to affect cognitive performance. We investigated mechanisms of possible radiation effects on IQ in two cohorts of 250 persons each: exposed n utero after the Chernobyl accident: a 'higher exposure group (HEG)', whose mothers resided in more heavily contaminated territories at the time of the Chernobyl accident, and a 'lesser exposure group (LEG)' whose mothers resided in less contaminated areas. The dataset included information on estimated prenatal thyroid radiation dose, gestation week at the time of the accident (ATA); thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine) levels measured at age 11-12 years and general IQ measured at three time points: t1: 6-7 years old; t2: 11-12 years old and t3: 15-16 years old. Descriptive and inference analyses were used to explore the dynamic of changes through time and the associations between key variables at the three time points. Estimated radiation doses to the thyroid gland were substantially higher in the HEG than in the LEG (mean 391 vs 25 mGy respectively). Significant differences in thyroid hormones levels were observed between the two groups, with lower values in T3 (higher in T4) in the LEG. At t1, the general IQ, as well as verbal and non-verbal IQ scores, were lower in the HEG than in the LEG. In the HEG, analyses adjusting simultaneously for radiation dose, gestational week ATA and T3 levels suggest that all three variables are associated with IQ, with the latter being highest among those exposed later during gestation and decreasing with increasing level of dose and of T3. No significant association was observed between IQ and T4 levels. No effect of exposure on IQ was seen in the LEG. Further investigation of this hypothesis will be important to understand the relation between n utero exposure radiation dose to thyroid, thyroid hormone levels and IQ, taking into account effects of potential confounding factors (physiological stress, maternal anxiety related evacuation).

We followed up persons exposed in utero to radiation from the Chernobyl accidentAmong the most highly exposed, IQ was higher among those exposed later during gestationAmong the most highly exposed, IQ also decreased with increasing level of dose and of T3No such relation was seen in those with lower exposureOur study provides insights into the possible relation between prenatal radiation dose and IQ and the factors which may modify it.

Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout.

INTRODUCTION: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure. METHODS: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose. RESULTS: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00-23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10-0.29 Gy compared to a dose of 0.00-0.09 Gy and decreased at doses of 0.3-24 Gy (p value for linear trend = 0.99). CONCLUSIONS: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure.

Recall of residential history and dietary habits during pregnancy and lactation in the distant past: reliability of questionnaire-based radiation doses for persons exposed in utero and early life.

This study evaluates the reliability of information obtained by standardized questionnaires used in by personal interviews for estimation of radiation thyroid doses of 1065 individuals in the Belarusian cohort of individuals who were exposed in utero and early life following the Chernobyl accident in April 1986. Data from two interviews conducted in 2012-2017 and in 2018-2022 with mothers, who were pregnant or gave birth shortly after the Chernobyl accident, were analysed. The most reliable answers dealt with various attributes related to residential history. In contrast, the reliability of answers regarding consumption rates of milk from privately owned cows or trade network was moderate, while the agreement in responses for consumption of milk products and leafy vegetables was fair. Information from the two interviews was used to calculate thyroid doses received by the cohort members. Specifically, 'model-based' thyroid doses due to 131I were estimated using input data on individual residential history and food consumption reported during the personal interviews and ecological data (131I ground deposition in the corresponding settlements). In addition, for a subset of cohort subjects (n = 205) whose mothers were measured for 131I thyroid activity, 'measurement-based' thyroid doses were calculated by adjusting the model-based dose using a scaling factor that is defined as the ratio of measured 131I thyroid activity to model-based 131I thyroid activity calculated for the date of measurement. A moderate agreement was observed for total (prenatal and postnatal) model-based thyroid doses due to 131I intake, the arithmetic mean ± standard deviation for the Jaccard similarity coefficient ([Formula: see text]) was 0.45 ± 0.34 (median = 0.39), while measurement-based doses showed a much better agreement with a [Formula: see text] of 0.78 ± 0.29 (median = 0.93). For model-based thyroid doses from external irradiation and from ingestion of 134Cs and 137Cs, [Formula: see text] was 0.82 ± 0.23 (median = 0.90) and 0.84 ± 0.24 (median = 0.96), respectively. Measurement-based doses due to ingestion of radiocaesium isotopes resulted in an almost perfect agreement, [Formula: see text] was 0.91 ± 0.19 (median = 1.0). The present findings suggest that long-term memory recall can be reliable, if a person is asked about unique or important life events, such as pregnancy and childbirth occurring around the time of a nuclear reactor accident. However, the substantial difference (more than 10 times) observed for model-bases doses calculated using the two questionnaires represents an important source of human factor uncertainties that needs to be considered in any dose response analyses. Other lessons learned from this study are that (i) individual measurements of radionuclides in the human body are the most valuable source of information for estimating radiation doses, and (ii) whenever a radiation accident occurs, a sample of affected people should be asked to keep a diary, if at all possible.

Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.

Background: Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations. Methods: We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population. Results: We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10-7, 2.39 × 10-7, and 7.19 × 10-7 and corresponding odds ratios of 2.02, 1.89, and 2.37. Conclusion: Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.

Assessment of Differentiated Thyroid Carcinomas in French Polynesia After Atmospheric Nuclear Tests Performed by France.

Importance: Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains a controversial issue in medicine and public health, and a misunderstanding of this issue may be associated with overdiagnosis of DTCs. Design, Setting, and Participants: This case-control study was conducted by extending a case-control study published in 2010 that included DTCs diagnosed between 1984 and 2003 by adding DTCs diagnosed between 2004 and 2016 and improving the dose assessment methodology. Data on 41 atmospheric nuclear tests conducted by France between 1966 and 1974 in French Polynesia (FP) were assessed from original internal radiation-protection reports, which the French military declassified in 2013 and which included measurements in soil, air, water, milk, and food in all FP archipelagos. These original reports led to an upward reassessment of the nuclear fallout from the tests and a doubling of estimates of the mean thyroid radiation dose received by inhabitants from 2 mGy to nearly 5 mGy. Included patients were diagnosed from 1984 to 2016 with DTC at age 55 years or younger and were born in and resided in FP at diagnosis; 395 of 457 eligible cases were included, and up to 2 controls per case nearest by birthdate and matched on sex were identified from the FP birth registry. Data were analyzed from March 2019 through October 2021. Exposure: The radiation dose to the thyroid gland was estimated using recently declassified original radiation-protection service reports, meteorological reports, self-reported lifestyle information, and group interviews of key informants and female individuals who had children at the time of these tests. Main Outcomes and Measures: The lifetime risk of DTC based on Biological Effects of Ionizing Radiation (BEIR) VII models was estimated. Results: A total of 395 DTC cases (336 females [85.1%]; mean [SD] age at end of follow-up, 43.6 [12.9] years) and 555 controls (473 females [85.2%]; mean [SD] age at end of follow-up, 42.3 [12.5] years) were included. No association was found between thyroid radiation dose received before age 15 years and risk of DTC (excess relative risk [ERR] per milligray, 0.04; 95% CI, -0.09 to 0.17; P = .27). When excluding unifocal noninvasive microcarcinomas, the dose response was significant (ERR per milligray, 0.09; 95% CI, -0.03 to 0.02; P = .02), but several incoherencies with the results of the initial study reduce the credibility of this result. The lifetime risk for the entire FP population was 29 cases of DTC (95% CI, 8-97 cases), or 2.3% (95% CI, 0.6%-7.7%) of 1524 sporadic DTC cases in this population. Conclusions and Relevance: This case-control study found that French nuclear tests were associated with an increase in lifetime risk of PTC in FP residents of 29 cases of PTC. This finding suggests that the number of thyroid cancer cases and the true order of magnitude of health outcomes associated with these nuclear tests were small, which may reassure populations of this Pacific territory.

Assessment of Uncertainties and Errors in Post-Chernobyl Dosimetry.

The present paper reviews the uncertainties and errors in complex dosimetry systems that were developed to estimate individual doses in different post-Chernobyl (Chornobyl) radiation epidemiology studies among the general population and the cleanup workers. These uncertainties and errors are associated with (i) instrumental radiation measurements of humans and environmental samples, (ii) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters, and (iii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, or missing responses during personal interview with study subjects conducted long after exposure. Relative measurement errors of 131I thyroid activity associated with devices for measuring radioactivity in the thyroid reached up to 0.86 (coefficient of variation). The inherent uncertainty in estimates of individual doses varied between different studies and exposure pathways (GSD from 1.2 to 15 for model-based doses and from 1.3 to 5.1 for measurement-based doses). The human factor uncertainties can cause individual doses to be underestimated or overestimated by an average of 10 times for model-based doses and 2 times for measurement-based doses calculated for the general population and up to 3 times for doses calculated for cleanup workers. The sources of errors and uncertainties, especially the human factor uncertainties, should be carefully considered in dose assessment for radiation epidemiological studies, with particular attention to studies involving persons without instrumental radiation measurements.

Exposure to the Thyroid from Intake of Radioiodine Isotopes after the Chornobyl Accident. Report I: Revised Doses and Associated Uncertainties for the Ukrainian-American Cohort.

Thyroid doses from intake of radioiodine isotopes (131I, 132Te+132I, and 133I) and associated uncertainties were revised for the 13,204 Ukrainian-American cohort members exposed in childhood and adolescence to fallout from the Chornobyl nuclear power plant accident. The main changes related to the revision of the 131I thyroid activity measured in cohort members, the use of thyroid-mass values specific to the Ukrainian population, and the revision of the 131I ground deposition densities in Ukraine. Uncertainties in doses were assessed considering shared and unshared errors in the parameters of the dosimetry model. Using a Monte-Carlo simulation procedure, 1,000 individual stochastic thyroid doses were calculated for each cohort member. The arithmetic mean of thyroid doses from intake of 131I, 132Te+132I, and 133I for the entire cohort was 0.60 Gy (median = 0.22 Gy). For 9,474 subjects (71.6% of the total), the thyroid doses were less than 0.5 Gy. Thyroid doses for 42 cohort members (0.3% of the total) exceeded 10 Gy while the highest dose was 35 Gy. Intake of 131I contributed around 95% to internal thyroid exposure from radioiodine isotopes. The geometric standard deviation of individual stochastic thyroid doses varied among cohort members from 1.4 to 4.3 with an arithmetic mean of 1.6 and a median of 1.4. It was shown that the contribution of shared errors to the dose uncertainty was small. The revised thyroid doses resulted, in average, in around 40% decrease for cohort members from Zhytomyr Oblast and an increase of around 24% and 35% for the cohort members from Kyiv and Chernihiv Oblast, respectively. Arithmetic mean of TD20 doses for the cohort was around 8% less than that estimated in TD10, 0.60 Gy vs. 0.65 Gy, respectively; however, global median of TD20 doses somewhat increased compared to TD10: 0.22 Gy vs. 0.19 Gy, respectively. The difference between TD10 and TD20 was mainly due to a revision of the individual 131I thyroid activity measured in the cohort members.

Breast cancer risk in Ukrainian women exposed to Chornobyl fallout while pregnant or lactating: standardized incidence ratio analysis, 1998 to 2016.

The radiation-related risk of breast cancer among women following the Chornobyl accident remains uncertain. During pregnancy, there is rapid cell proliferation in the breast while radioactive iodine from fallout exposure can concentrate in lactating breast tissues. We conducted a standardized incidence ratio (SIR) analysis of breast cancer in a cohort of 2,631 women who were lactating and/or pregnant at any time during the 2-month period of radioiodine fallout (April 26, 1986-June 30, 1986). There were 37,151 person-years of follow-up, and 26 incident breast cancers were identified through linkage with the National Cancer Registry of Ukraine. Breast cancer rates among pregnant or lactating women were compared to the general population rates, and SIRs were adjusted for oblast, urban/rural, age, and calendar year. The SIR was not significant for women pregnant at the time of the accident (SIR = 0.75; 95% CI 0.44, 1.18) or for women lactating anytime within 2 months of the accident (SIR = 0.96; 95% CI 0.48, 1.68). However, there was a non-significantly elevated risk for women lactating at the time of accident (SIR = 1.30, 95% CI 0.40, 3.01). The increased SIR for breast cancer among lactating women is consistent with the results of a similar study in Belarus and indicates the need to quantify the radiation risk of breast cancer in a larger study of women lactating during the period of fallout exposure.

Evaluation of 131I transfer in the environment based on the available measurements made in Belarus after the Chernobyl accident.

This study evaluates the 131I transfer from ground deposition to the human thyroid gland after the Chernobyl accident using measurements of 131I concentrations in 1,252 soil, 124 grass, and 136 cow's milk samples as well as 131I thyroid activity measured in 3,100 individuals included in the Belarusian-American cohort. The following parameters of an 131I environmental transfer model used to calculate thyroid doses were evaluated in this study: (i) the interception factor of 131I by pasture grass, which was described by a purely empirical equation, (ii) the removal rate of 131I from pasture grass due to weathering and growth dilution, estimated to be 0.0676 d-1 (half-life of 10.3 d), (iii) the removal rate of 131I from cow's milk, estimated to be 0.0686 d-1 (half-life of 10.1 d), and (iv) the transfer coefficient of 131I from feed to cow's milk, arithmetic mean ± standard deviation of (6.7 ± 8.7) × 10-3 d L-1 (median = 4.0 × 10-3 d L-1). The individual model-based and measurement-based 131I thyroid activities for the Belarusian-American cohort members were calculated using different starting points of 131I transfer in the chain 'ground deposition' → 'vegetation' → 'cow's milk' → 'human thyroid', i.e., the measured 131I concentrations in soil, grass, and cow's milk. De novo thyroid doses from 131I for the 3,100 cohort members were calculated in this study using measured 131I activity concentrations in soil, grass, and cow's milk and were compared with those estimated previously for the same individuals using model-based 131I activity concentrations. It was shown that the use of measured instead of model-based 131I concentrations, in general, did not improve the measurement-based thyroid dose estimates. This is likely to be because there was already a good generic data base for the parameters used in this assessment. This finding indicates that, although the measurements of environmental samples are essential to estimate the parameter values of the 131I transfer model, the individual measurements of 131I thyroid activity are the most valuable information for estimating individual thyroid doses.

Doses from external irradiation and ingestion of 134Cs, 137Cs and 90Sr of the population of Belarus accumulated over 35 years after the Chernobyl accident.

This study considers the exposure of the population of the most contaminated Gomel and Mogilev Oblasts in Belarus to prolonged sources of irradiation resulting from the Chernobyl accident. Dose reconstruction methods were developed and applied in this study to estimate the red bone-marrow doses (RBMs) from (i) external irradiation from gamma-emitting radionuclides deposited on the ground and (ii) 134Cs, 137Cs and 90Sr ingestion with locally produced foodstuffs. The mean population-weighted RBM doses accumulated during 35 years after the Chernobyl accident were 12 and 5.7 mGy for adult residents in Gomel and Mogilev Oblasts, respectively, while doses for youngest age groups were 20-40% lower. The highest mean area-specific RBM doses for adults accumulated in 1986-2021 were 63, 56 and 46 mGy in Narovlya, Vetka and Korma raions in Gomel Oblast, respectively. For most areas, external irradiation was the predominant pathway of exposure (60-70% from the total dose), except for areas with an extremely high aggregated 137Cs soil to cow's milk transfer coefficient (≥ 5.0 Bq L-1 per kBq m-2), where the contribution of 134Cs and 137Cs ingestion to the total RBM dose was more than 70%. The contribution of 90Sr intake to the total RBM dose did not exceed 4% for adults and 10% for newborns in most raion in Gomel and Mogilev Oblasts. The validity of the doses estimated in this study was assessed by comparison with doses obtained from measurements by thermoluminescence dosimeters and whole-body counters done in 1987-2015. The methodology developed in this study can be used to calculate doses to target organs other than RBM such as thyroid and breast doses. The age-dependent and population-weighted doses estimated in this study are useful for ecological epidemiological studies, for projection of radiation risk, and for justification of analytical epidemiological studies in populations exposed to Chernobyl fallout.

Reliability of Questionnaire-Based Dose Reconstruction: Human Factor Uncertainties in the Radiation Dosimetry of Chernobyl Cleanup Workers.

This original study aims to quantify the human factor uncertainties in radiation doses for Chernobyl cleanup workers that are associated with errors in direct or proxy personal interviews due to poor memory recall a long time after exposure. Two types of doses due to external irradiation during cleanup mission were calculated independently. First, a "reference" dose, that was calculated using the historical description of cleanup activities reported by 47 cleanup workers shortly after the completion of the cleanup mission. Second, a "current" dose that was calculated using information reported by 47 cleanup workers and respective 24 proxies (colleagues) nominated by cleanup workers during a personal interview conducted more recently, as part of this study, i.e., 25-30 years after their cleanup missions. The Jaccard similarity coefficient for reference and current doses was moderate: the arithmetic mean ± standard deviation was 0.29 ± 0.18 (median = 0.31) and 0.23 ± 0.18 (median = 0.22) for the cleanup worker's and proxy's interviews, respectively. The agreement between two doses was better if the cleanup worker was interviewed rather than his proxy: the median ratio of current to reference dose was 1.0 and 0.56 for cleanup workers and proxies, respectively. The present study has shown that human factor uncertainties lead to underestimation or overestimation of the "true" reference dose for most cleanup workers up to 3 times. In turn, the potential impact of these errors on radiation-related risk estimates should be assessed.

Assessment of internal exposure to 131I and short-lived radioiodine isotopes and associated uncertainties in the Ukrainian cohort of persons exposed in utero.

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.

Impact of uncertainties in exposure assessment on thyroid cancer risk among cleanup workers in Ukraine exposed due to the Chornobyl accident.

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.

Association between exposure to radioactive iodine after the Chernobyl accident and thyroid volume in Belarus 10-15 years later.

BACKGROUND: While there is a robust literature on environmental exposure to iodine-131 (131I) 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 131I 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 131I 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.

Risk of thyroid cancer in Ukrainian cleanup workers following the Chornobyl accident.

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.

Breast cancer risk in residents of Belarus exposed to Chernobyl fallout while pregnant or lactating: standardized incidence ratio analysis, 1997 to 2016.

BACKGROUND: Pregnancy and lactation may constitute radiation-sensitive reproductive periods due to rapid cell proliferation and concentration of radioiodine in the lactating breast. However, there are limited epidemiological data among women exposed to radiation during these periods. METHODS: We examined incidence of breast cancer in a cohort of 3214 women who were pregnant and/or lactating within 2 months (26 April to 30 June 1986) of the Chernobyl accident and residing in contaminated regions of Belarus. There were 33 breast cancers identified through linkage with the Belarusian National Cancer Registry. Breast cancer rates among women who were either pregnant and/or lactating were compared with population rates by calculating standardized incidence ratios (SIR) and 95% confidence intervals (CI) adjusting for attained age, oblast, urban/rural residence and calendar year. RESULTS: Among women who were lactating, we found a greater than 2-fold increased risk of breast cancer compared with the general population, SIR = 2.49 (95% CI: 1.55, 3.75). In contrast, women who were pregnant were not at increased risk (SIR = 0.84 95% CI: 0.46, 1.38). The SIR was highest in women who were exposed at a younger age and at the earliest time period since the accident, though stratified analyses had limited sample sizes. CONCLUSIONS: We found a significantly increased risk of breast cancer among women residing in contaminated areas of Belarus who were lactating at the time of the accident and may have had elevated exposure to radioiodine, when compared with the general population. Studies of breast cancer with individual radiation dose estimates among women exposed during lactation are warranted.