Environmental radiation exposure at Chornobyl has not systematically affected the genomes or chemical mutagen tolerance phenotypes of local worms.

The 1986 disaster at the Chornobyl Nuclear Power Plant transformed the surrounding region into the most radioactive landscape known on the planet. Whether or not this sudden environmental shift selected for species, or even individuals within a species, that are naturally more resistant to mutagen exposure remains an open question. In this study, we collected, cultured, and cryopreserved 298 wild nematode isolates from areas varying in radioactivity within the Chornobyl Exclusion Zone. We sequenced and assembled genomes de novo for 20 Oscheius tipulae strains, analyzed their genomes for evidence of recent mutation acquisition in the field, and observed no evidence of an association between mutation and radioactivity at the sites of collection. Multigenerational exposure of each of these strains to several chemical mutagens in the lab revealed that strains vary heritably in tolerance to each mutagen, but mutagen tolerance cannot be predicted based on the radiation levels at collection sites, and Chornobyl isolates were not systematically more resistant than strains from undisturbed habitats. In sum, the absence of mutational signatures does not reflect unique capacity for tolerating DNA damage.

Identifying Genomic Signatures of Positive Selection to Predict Protective Genomic Loci in the Cohort of Lithuanian Clean-Up Workers of the Chornobyl Nuclear Disaster.

Some people resist or recover from health challenges better than others. We studied Lithuanian clean-up workers of the Chornobyl nuclear disaster (LCWC) who worked in the harshest conditions and, despite high ionising radiation doses as well as other factors, continue ageing relatively healthily. Thus, we hypothesised that there might be individual features encoded by the genome which act protectively for better adaptiveness and health that depend on unique positive selection signatures. Whole-genome sequencing was performed for 40 LCWC and a control group composed of 25 men from the general Lithuanian population (LTU). Selective sweep analysis was performed to identify genomic regions which may be under recent positive selection and determine better adaptiveness. Twenty-two autosomal loci with the highest positive selection signature values were identified. Most important, unique loci under positive selection have been identified in the genomes of the LCWC, which may influence the survival and adaptive qualities to extreme conditions, and the disaster itself. Characterising these loci provide a better understanding of the interaction between ongoing microevolutionary processes, multifactorial traits, and diseases. Studying unique groups of disease-resistant individuals could help create new insights for better, more individualised, disease diagnostics and prevention strategies.

Preliminary assessment of the radiological consequences of the hostile military occupation of the Chornobyl Exclusion Zone.

The full-scale invasion of Ukraine by Russian military forces on 24 February 2022 put the radiological well-being of the people in Ukraine under unprecedented threat. Apart from the risks linked to operating nuclear power plants, there was substantial evidence of looting of facilities of all kinds, including those holding radioactive materials, as well as the scope for physical disturbance of radioactively contaminated areas and waste storage facilities. The actions of Russian military personnel invading Ukraine through the territory of the Chornobyl Exclusion Zone (the ChEZ) were of serious concern. Before its shutdown a few days after the beginning of the occupation, the automated radiation monitoring system of the ChEZ recorded sharp increases in the gamma-background in several areas which indicated some non-typical processes taking place on its territory. The State Nuclear Regulatory Inspectorate of Ukraine (SNRIU) and its technical support organisation, the Scientific and Technical Centre for Nuclear and Radiation Safety (SSTC NRS), as well as the rest of the professional nuclear community in Ukraine and worldwide, recognised the potential for movement of the radioactive contamination (reaching 101-104kBq m-2Cs-137 in the most of the territory) by the Russian military machinery and personnel to areas outside the ChEZ, creating locally contaminated spots along the routes taken by the invaders towards Kyiv. Certain apprehensions were caused by the inventory carried out after the liberation of the ChEZ which revealed the theft of calibration sources and radioactive samples from laboratories located in Chornobyl. As soon as this information became available to the public, it caused a wide response and anxiety, as a result of which SNRIU made a decision to conduct a radiation survey of the liberated territories in the Kyiv region. The survey was conducted between June and December 2022 by SSTC NRS specialists with the support of DSA. The scope of the survey was limited by available time and resources; however, the total route of the survey was about 840 km, and covered more than 50 settlements and a limited part of the ChEZ. The radiation survey combined the continuous gamma-dose rate measurements by the detectors installed in the laboratory vehicle and additional manual measurements at specified points. As a result of the radiation survey, no deterioration of the radiation situation was observed in the liberated territories. No contaminated objects, radiation sources, or other radioactive material removed from the ChEZ were found either. Measurements of the Cs-137 soil contamination in the ChEZ, although limited, corresponded to the results which had been obtained before the war. It can be concluded that in the surveyed territories, the direct impact on the public in the form of additional radioactive contamination removed from the ChEZ in February-March 2022 was negligible. The same applies to the radiation consequences of forest fires that occurred in the ChEZ during its occupation. However, due to the damage of the radiation monitoring system, explosive hazard, and destruction of transport infrastructure, the consequences of the occupation of the ChEZ by Russian troops will be long-term.

Some observations on meaningful and objective inference in radioecological field studies.

Anthropogenic releases of radiation are of ongoing importance for environmental protection, but the radiation doses at which natural systems begin to show effects are controversial. More certainty is required in this area to achieve optimal regulation for radioactive substances. We recently carried out a large survey (268 sampled animals and 20 sites) of the association between environmental radiation exposures and small mammal gut-associated microbiomes (fungal and bacterial) in the Chornobyl Exclusion zone (CEZ). Using individual measurements of total absorbed dose rates and a study design and analyses that accounted for spatial non-independence, we found no, or only limited, association. Watts et al. have criticised our study: for not filtering candidate non-resident components prior to our fungal microbiome analyses, for our qualified speculations on the relative merits of faecal and gut samples, and for the design of our study which they felt lacked sufficient replication. The advantage of filtering non-resident-fungal taxa is not clear and it would not have changed the null (spatially adjusted) association we found between radioactive dose and mycobiome composition because the most discriminatory fungal taxa with regard to dose were non-resident taxa. We maintain that it was legitimate for us to make qualified discussion comments on the differences in results between our faecal and gut microbiome analyses and on the relative merits of these sample types. Most importantly, the criticism of our study design by Watts et al. and the designs and analysis of their recent studies in the CEZ show a misunderstanding of the true nature of independent replication in field studies. Recognising the importance of spatial non-independence is essential in the design and analysis of radioecological field surveys.

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.

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.

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 incidence in the regions of Belarus and Ukraine most contaminated by the Chernobyl accident: 1978 to 2016.

Even 30 years after the accident, an association between breast cancer incidence and ionizing radiation exposure from Chernobyl fallout remains uncertain. We studied breast cancer incidence in the most contaminated regions of Belarus (Gomel and Mogilev) and Ukraine (Kyiv, Zhytomyr and Chernihiv) before (1978-1986) and after (1987-2016) the accident. Breast cancer cases and female population size data were received from the national cancer registries and the state departments of statistics. The study included 85 132 breast cancers with 150 million person-years at risk. We estimated annual rayon (district)-average absorbed doses to the breast from external and internal irradiation of the adult female population over the period of 1986-2016. We studied an association between rayon-average cumulative absorbed breast dose with 5-year lag, that is, excluding the exposure in 5 years prior to breast cancer diagnosis, and breast cancer incidence using negative binomial regression models. Mean (median) cumulative breast dose in 2016 was 12.3 (5.0) milligray (mGy) in Belarus and 5.7 (2.3) mGy in Ukraine, with the maximum dose of 55 mGy and 54 mGy, respectively. Breast cancer incidence rates statistically significantly increased with calendar year and attained age, and were higher in urban than in rural residents. Adjusting for time, age and urbanicity effects, we found no evidence of increasing incidence with rayon-average 5-year lagged cumulative breast dose. Owing to ecological study design limitations, a case-control study covering this area with individually reconstructed absorbed breast doses is needed testing for association between low-dose protracted radiation exposure and breast cancer risk after Chernobyl.

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population.

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised 131I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of 131I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of 131I thyroid activity among their residents. Thyroid doses due to 131I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol. Among them, dose estimates for 835 settlements were based on 131I thyroid activities measured in more than ten residents (the first level), for 690 settlements based on such measurements done in neighboring settlements (the second level), and for 28,828 settlements based on a purely empirical relationship between the thyroid doses due to 131I intake and the cumulative 131I ground deposition densities in settlements (the third level). The arithmetic mean of the thyroid doses due to 131I intake among 146,425 measured individuals was 0.23 Gy (median of 0.094 Gy); about 99.8% of them received doses less than 5 Gy. The highest oblast-average population-weighted thyroid doses were estimated for residents of Chernihiv (0.15 Gy for arithmetic mean and 0.060 Gy for geometric mean), Kyiv (0.13 and 0.051 Gy) and Zhytomyr (0.12 and 0.049 Gy) Oblasts followed by Rivne (0.10 and 0.039 Gy) and Cherkasy (0.088 and 0.032 Gy) Oblasts, and Kyiv City (0.076 and 0.031 Gy). The geometric mean of thyroid doses estimated in this study for the entire Ukraine essentially did not change in comparison with a previous estimate, 0.020 vs. 0.021 Gy, respectively. The ratio of geometric mean of oblast-specific thyroid doses estimated in the present study to previously calculated doses varied from 0.51 to 3.9. The highest increase in thyroid doses was found in areas remote from the Chornobyl nuclear power plant with a low level of radioactive contamination: by 3.9 times for Zakarpatska Oblast, 3.5 times for Luhansk Oblasts and 2.9 times for Ivano-Frankivsk Oblast. The developed thyroid dosimetry system is being used to revise the thyroid doses due to 131I intake for the individuals of post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort, and the Chornobyl Tissue Bank.

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report I: revision of direct thyroid measurements.

The increased risk of thyroid cancer among individuals exposed during childhood and adolescence to Iodine-131 (131I) is the main statistically significant long-term effect of the Chornobyl accident. Several radiation epidemiological studies have been carried out or are currently in progress in Ukraine, to assess the risk of radiation-related health effects in exposed populations. About 150,000 measurements of 131I thyroid activity, so-called 'direct thyroid measurements', performed in May-June 1986 in the Ukrainian population served as the main sources of data used to estimate thyroid doses to the individuals of these studies. However, limitations in the direct thyroid measurements have been recently recognized including improper measurement geometry and unknown true values of calibration coefficients for unchecked thyroid detectors. In the present study, a comparative analysis of 131I thyroid activity measured by calibrated and unchecked devices in residents of the same neighboring settlements was conducted to evaluate the correct measurement geometry and calibration coefficients for measuring devices. As a result, revised values of 131I thyroid activity were obtained. On average, in Vinnytsia, Kyiv, Lviv and Chernihiv Oblasts and in the city of Kyiv, the revised values of the 131I thyroid activities were found to be 10-25% higher than previously reported, while in Zhytomyr Oblast, the values of the revised activities were found to be lower by about 50%. New sources of shared and unshared errors associated with estimates of 131I thyroid activity were identified. The revised estimates of thyroid activity are recommended to be used to develop an updated Thyroid Dosimetry system (TD20) for the entire population of Ukraine as well as to revise the thyroid doses for the individuals included in post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort and the Chornobyl Tissue Bank.

Estimation of radiation gonadal doses for the American-Ukrainian trio study of parental irradiation in Chornobyl cleanup workers and evacuees and germline mutations in their offspring.

Radiation doses of parents exposed from the Chornobyl accident as cleanup workers or evacuees were estimated in the National Cancer Institute-National Research Center for Radiation Medicine trio (i.e. father, mother, offspring) study aimed at investigating the radiation effects on germlinede novomutations in children as well as other outcomes. Paternal (testes) and maternal (ovaries) gonadal doses were calculated along with associated uncertainty distributions for the following exposure pathways: (a) external irradiation during the cleanup mission, (b) external irradiation during residence in Pripyat, and (c) external irradiation and (d) ingestion of radiocesium isotopes, such as134Cs and137Cs, during residence in settlements other than Pripyat. Gonadal doses were reconstructed for 298 trios for the periods from the time of the accident on 26 April 1986 to two time points before the child's date of birth (DOB): 51 (DOB-51) and 38 (DOB-38) weeks. The two doses, DOB-51 and DOB-38 were equal (within 1 mGy) in most instances, except for 35 fathers where the conception of the child occurred within 3 months of exposure or during exposure. The arithmetic mean of gonadal DOB-38 doses was 227 mGy (median: 11 mGy, range 0-4080 mGy) and 8.5 mGy (median: 1.0 mGy, range 0-550 mGy) for fathers and mothers, respectively. Gonadal doses varied considerably depending on the exposure pathway, the highest gonadal DOB-38 doses being received during the cleanup mission (mean doses of 376 and 34 mGy, median of 144 and 7.4 mGy for fathers and mothers, respectively), followed by exposure during residence in Pripyat (7.7 and 13 mGy for mean, 7.2 and 6.2 mGy for median doses) and during residence in other settlements (2.0 and 2.1 mGy for mean, 0.91 and 0.81 mGy for median doses). Monte Carlo simulations were used to estimate the parental gonadal doses and associated uncertainties. The geometric standard deviations (GSDs) in the individual parental stochastic doses due to external irradiation during the cleanup mission varied from 1.2 to 4.7 (mean of 1.8), while during residence in Pripyat they varied from 1.4 to 2.8 (mean of 1.8), while the mean GSD in doses received during residence in settlements other than Pripyat was 1.3 and 1.4 for external irradiation and ingestion of radiocesium isotopes, respectively.

Field Study of the Possible Effect of Parental Irradiation on the Germline of Children Born to Cleanup Workers and Evacuees of the Chornobyl Nuclear Accident.

Although transgenerational effects of exposure to ionizing radiation have long been a concern, human research to date has been confined to studies of disease phenotypes in groups exposed to high doses and high dose rates, such as the Japanese atomic bomb survivors. Transgenerational effects of parental irradiation can be addressed using powerful new genomic technologies. In collaboration with the Ukrainian National Research Center for Radiation Medicine, the US National Cancer Institute, in 2014-2018, initiated a genomic alterations study among children born in selected regions of Ukraine to cleanup workers and/or evacuees exposed to low-dose-rate radiation after the 1986 Chornobyl (Chernobyl) nuclear accident. To investigate whether parental radiation exposure is associated with germline mutations and genomic alterations in the offspring, we are collecting biospecimens from father-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number changes, structural variants, genomic insertions and deletions, methylation profiles, and telomere length. Genomic alterations are being examined in relation to parental gonadal dose, reconstructed using questionnaire and measurement data. Subjects are being recruited in exposure categories that will allow examination of parental origin, duration, and timing of exposure in relation to conception. Here we describe the study methodology and recruitment results and provide descriptive information on the first 150 families (mother-father-child(ren)) enrolled.

Childhood leukemia in Ukraine after the Chornobyl accident.

This population-based ecological study analyzes the prevalence of childhood leukemia in Ukraine before and after the Chornobyl nuclear power plant accident, based on the contamination status of the territory, time period, gender, and age. Three regions-Zhytomyr, Kyiv (except Kyiv city), and Chernihiv were included as areas contaminated by radioactive 137Cs from 1 to 15 Ci/km2 with annual effective doses exceeding 1.0 mSv, and Sumy region as the control (non-contaminated) area with 137Cs contamination less than 1 Ci/km2 and effective doses less than 0.5 mSv per year. The integrated database of the National Research Centre for Radiation Medicine used in the present study included 1085 childhood leukemia cases. Two aggregated periods were used for analysis: 1980-1986 (pre-accident) and 1987-2000 (post-accident). ICD-9 codes for leukemia (204-208.9) were used to perform analyses according to the extent of leukemic cells maturity (acute, chronic, and maturity unspecified leukemia), leukemic cell lineage (lymphoid, myeloid and lineage unspecified leukemia) and all leukemia cases in different age subgroups (1-4, 5-9, 10-14, and 15-19 years). Standard methods of descriptive epidemiology were used to calculate the prevalence of disease and frequency ratio in regression models. A statistically significant increase in frequency ratio for acute leukemia (1.44; 95% confidence interval (CI), 1.22-1.71), myeloid leukemia (2.93; 95% CI, 1.71-5.40), cell lineage unspecified leukemia (II) (1.48; 95% CI, 1.18-1.87) and all forms of leukemia (1.59; 95% CI, 1.36-1.86) was found for the post-accident period in highly contaminated areas. The results indicate that the frequency of childhood leukemia (and of some of its types) increased in contaminated areas during the post-accident period, suggesting that radiation exposure after the Chornobyl accident might be the cause of the increase. However, further analytical studies, with individual or at least group dose estimates, are needed to confirm a link between childhood leukemia and the Chornobyl accident.

Genomic characterization of chronic lymphocytic leukemia (CLL) in radiation-exposed Chornobyl cleanup workers.

BACKGROUND: Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. METHODS: A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively). RESULTS: Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p < 0.05). No significant enrichment in copy-number abnormalities at del13q14, del11q, del17p or trisomy12 was identified in UR-CLL compared to other groups. Type of work performed in the Chornobyl zone, age at exposure and at diagnosis, calendar time, and Rai stage were significant predictors of total genetic lesions (all p < 0.05). Tumor telomere length was significantly longer in UR-CLL than in UN-CLL (p = 0.009) and was associated with the POT1 mutation and survival. CONCLUSIONS: No significant enrichment in copy-number abnormalities at CLL-associated genes was identified in UR-CLL compared to other groups. The novel associations between radiation exposure, telomere maintenance and CLL prognosis identified in this unique case series provide suggestive, though limited data and merit further investigation.

Estimation of radiation risk in presence of classical additive and Berkson multiplicative errors in exposure doses.

In this paper, the influence of measurement errors in exposure doses in a regression model with binary response is studied. Recently, it has been recognized that uncertainty in exposure dose is characterized by errors of two types: classical additive errors and Berkson multiplicative errors. The combination of classical additive and Berkson multiplicative errors has not been considered in the literature previously. In a simulation study based on data from radio-epidemiological research of thyroid cancer in Ukraine caused by the Chornobyl accident, it is shown that ignoring measurement errors in doses leads to overestimation of background prevalence and underestimation of excess relative risk. In the work, several methods to reduce these biases are proposed. They are new regression calibration, an additive version of efficient SIMEX, and novel corrected score methods.

Clinical characteristics of chronic lymphocytic leukemia occurring in chornobyl cleanup workers.

The recently demonstrated radiation-induction of chronic lymphocytic leukemia (CLL) raises the question as to whether the amount of radiation exposure influences any of the clinical characteristics of the disease. We evaluated the relationship between bone marrow radiation doses and clinical characteristics and survival of 79 CLL cases diagnosed during 1986-2006 in a cohort of 110 645 male workers who participated in the cleanup work of the Chornobyl nuclear accident in Ukraine in 1986. All diagnoses were confirmed by an independent International Hematology Panel. Patients were followed up to the date of death or end of follow-up on 31 October 2010. The median age at diagnosis was 57 years. Median bone marrow dose was 22.6 milligray (mGy) and was not associated with time between exposure and clinical diagnosis of CLL (latent period), age, peripheral blood lymphocyte count or clinical stage of disease in univariate and multivariate analyses. Latent period was significantly shorter among those older at first exposure, smokers and those with higher frequency of visits to the doctor prior to diagnosis. A significant increase in the risk of death with increasing radiation dose was observed (p = 0.03, hazard ratio = 2.38, 95% confidence interval: 1.11,5.08 comparing those with doses ≥22 mGy to doses <22 mGy). After adjustment for radiation dose, survival of CLL cases was significantly shorter among those with younger age at first exposure, higher peripheral blood lymphocyte count, more advanced clinical stage of disease and older age at diagnosis (all p < 0.05). This is the first study to examine association between bone marrow radiation doses from the Chornobyl accident and clinical manifestations of the CLL in Chornobyl cleanup workers. The current study provides new evidence on the association of radiation dose and younger age at first radiation exposure at Chornobyl with shorter survival after diagnosis. Future studies are necessary with more cases in order to improve the statistical power of these analyses and to determine their significance. Copyright © 2016 John Wiley & Sons, Ltd.

Buccal mucosa micronuclei counts in relation to exposure to low dose-rate radiation from the Chornobyl nuclear accident and other medical and occupational radiation exposures.

BACKGROUND: Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure. METHODS: Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion. RESULTS: Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures. CONCLUSIONS: There are indications of increasing trends of micronuclei prevalence with Chornobyl-cleanup-associated dose, and indications of reduction in radiation-associated excess prevalence of micronuclei with time after exposure. There are also indications of substantially increased micronuclei associated with work as an industrial radiographer. This analysis adds to the understanding of the long-term effects of low-dose radiation exposures on relevant cellular structures and methods appropriate for long-term radiation biodosimetry.

Elevated congenital anomaly rates and incorporated cesium-137 in the Polissia region of Ukraine.

BACKGROUND: Investigations soon after the 1986 Chornobyl (Chernobyl in Russian) accident of exposed populations residing elsewhere in Europe led government and international agencies to conclude that exposures to cesium-137 (Cs-137) were not teratogenic. Our observations of elevated population rates of neural tube defects (NTDs) and microcephaly and microphthalmia (M/M) in the Rivne Province in Ukraine, which were among the highest in Europe, prompted this follow-up investigation inclusive of whole-body counts (WBCs) of Cs-137 among ambulatory patients and pregnant women residing in Polissia, the most polluted region in Rivne. METHODS: Yearly (2000-2012) population rates of NTDs and M/M and WBC patterns of ambulatory patients (2001-2010) and pregnant women (2011-2013) in Polissia and non-Polissia regions of Rivne were analyzed. RESULTS: The NTD and M/M population rates in Rivne remain elevated and are statistically significantly higher in Polissia than in non-Polissia. The WBCs among residents in Polissia are statistically significantly higher than among those from non-Polissia. CONCLUSION: NTD and M/M rates are highest in the Polissia region of Rivne and are among the highest in Europe. In Polissia, the WBCs of Cs-137 are above officially set permissible upper limits. The results are based on aggregate data of NTDs and M/Ms and average WBC values. Further investigations of causality of the high rates of NTDs and M/Ms are needed and urgent strengthening policies and implementations to reduce exposures to teratogens, in particular radioactive nuclides and alcohol, and consumption of folic acid supplements are indicated.

Risk of thyroid follicular adenoma among children and adolescents in Belarus exposed to iodine-131 after the Chornobyl accident.

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at <2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure.

Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

BACKGROUND: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. METHODS: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. RESULTS: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. CONCLUSIONS: These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products.