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.

     

Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties in Bryansk Oblast, Russia: a population-based case-control study

A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources.     

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.     

Thyroid cancer risk in areas of Ukraine and Belarus affected by the Chernobyl accident

The purpose of the present study was to analyze the thyroid cancer incidence risk after the Chernobyl accident and its degree of dependence on time and age. Data were analyzed for 1034 settlements in Ukraine and Belarus, in which more than 10 measurements of the (131)I content in human thyroids had been performed in May/June 1986. Thyroid doses due to the Chernobyl accident were assessed for the birth years 1968-1985 and related to thyroid cancers that were surgically removed during the period 1990-2001. The central estimate for the linear coefficient of the EAR dose response was 2.66 (95% CI: 2.19; 3.13) cases per 10(4) PY-Gy; for the quadratic coefficient, it was -0.145 (95% CI: -0.171; -0.119) cases per 10(4) PY-Gy(2). The EAR was found to be higher for females than for males by a factor of 1.4. It decreased with age at exposure and increased with age attained. The central estimate for the linear coefficient of the ERR dose response was 18.9 (95% CI: 11.1; 26.7) Gy(-1); for the quadratic coefficient, it was -1.03 (95% CI: -1.46; -0.60) Gy(-2). The ERR was found to be smaller for females than for males by a factor of 3.8 and decreased strongly with age at exposure. Both EAR and ERR were higher in the Belarusian settlements than in the Ukrainian settlements. In contrast to ERR, EAR increases with time after exposure. At the end of the observation period, excess risk estimates were found to be close to those observed in a major pooled analysis of seven studies of childhood thyroid cancer after external exposures.     

Post-Chornobyl thyroid cancers in Ukraine. Report 1: estimation of thyroid doses

About 1.8 EBq of 131I was released into the atmosphere during the Chornobyl accident that occurred in Ukraine on April 26, 1986. More than 10% of this activity was deposited on the territory of Ukraine. Beginning 4-5 years after the accident, an increase in the incidence of thyroid cancer among children, believed to be caused in part by exposure to 131I, has been observed in different regions of Ukraine. A three-level system of thyroid dose estimation was developed for the reconstruction of thyroid doses from 131I for the entire population of Ukrainian children aged 1 to 18 at the time of accident: (1) At the first level, individual doses were estimated for the approximately 99,000 children and adolescents with direct measurements of radioactivity in the thyroid (so-called direct thyroid measurements) performed in May-June of 1986; (2) at the second level, group doses by year of age and by gender were estimated for the population of 748 localities (with 208,400 children aged 1-18 in 1986) where direct thyroid measurements of good quality were performed on some of the residents; and (3) at the third level, group doses by age and by gender were estimated for the population of the localities where no thyroid measurements were made in 1986. The third-level doses were then aggregated over the population of each oblast. Data, models and procedures required for each level of thyroid dose estimation are described in the paper. At the first level, individual doses were found to range up to 27,000 mGy, with geometric and arithmetic means of 100 and 300 mGy, respectively. At the second level, group doses were found to be highest for the younger children (aged 1 to 4 years); doses for the older children (aged 16 to 18 years) were 3.5 times smaller. At the third level, average population-weighted doses were found to exceed 35 mGy in the five northern oblasts closer to the Chornobyl reactor site; to be in the 14- to 34-mGy range in seven other oblasts, Kyiv city and Crimea; and to be less than 13 mGy in all other oblasts.     

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.     

15 years after the accident at the Chernobyl Nuclear Power Plant

Health effects as a result of the accident at the Chernobyl nuclear power plant occurred in 1986 are considered in the paper. Wrong prognosis of the health effects with respect to mortality and morbidity among the population exposed to low radiation doses is shown. Proven increase in thyroid cancer cases among people who were children aged from 0 to 18 at the time of the accident is shown. Linear relationship between thyroid cancer cases and dose to thyroid ranged from 0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the fifteen years following the accident no cases of acute and chronic radiation sickness have been revealed because the population living in contaminated areas received low radiation doses. Also, exposures to low radiation doses did not result in excess of malignant tumors among population. In some cases the outcomes of acute radiation sickness were as follows: radiation damages to the skin, cancer cataracts, development of oncopathology.     

Thyroid dose assessment for the Chernigov region (Ukraine): Estimation based on131I thyroid measurements and extrapolation of the results to districts without monitoring

Based on the results of¹³¹I thyroid activity measurements in three districts of the Chernigov region (Ukraine), individual doses were calculated and an approach of the age dependence of the average thyroid exposure was derived. Using the relationships between the thyroid doses and the¹³⁷Cs deposition as well as the location relative to the Chernobyl Nuclear Power Plant (NPP), age-dependent average thyroid doses were extrapolated also for those settlements of this region where no monitoring measurements have been carried out. The highest doses were found in the west of the region with the lowest distance to the Chernobyl NPP. In this part, the highest mean of the thyroid dose in a settlement was 3.3 Gy for infants and 0.5 Gy for adults. The collective thyroid dose was 31000 and 27 000 person-Gy for children and adults, respectively. Based on this assessment, 140 and 21 excess thyroid cancer cases are predicted for children and adults, respectively. In the years 1989 to 1991, in the whole contaminated territory of the Ukraine 0.4–1.2 cases per 100000 children were observed. Although the absolute numbers are very small, this indicates the possibility of an increase in thyroid cancer morbidity among children. The same trend also seems to be indicated in the Chernigov region. A careful epidemiological study in the future is necessary to enable a final evaluation of radioinduced cancers in this region.     

Non-malignant thyroid diseases after a wide range of radiation exposures

The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. The aim of this review is to evaluate the effects of high- and low-dose radiation on benign structural and functional diseases of the thyroid. We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate- to high-dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation, and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. After a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades after exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak, and significant radiation effects were most often observed after high doses, particularly for hypothyroidism. A significant radiation dose-response relationship was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties encountered in studying these diseases.     

Thyroid cancer incidence in Ukraine: trends with reference to the Chernobyl accident

For the first time, a comparative analysis of thyroid cancer incidence in Ukraine after the Chernobyl accident was done in a cohort that is almost as large as the general population. On the basis of thyroid doses from radioactive iodine in individuals aged 1-18 years at the time of accident, geographic regions of Ukraine with low and high average accumulated thyroid doses were established and designated "low-exposure" and "high-exposure" territories, respectively. A significant difference of thyroid cancer incidence rates as a function of time between the two territories was found. That is, the increase in the incidence was higher in high-exposure regions than in low-exposure regions. The incidence rates varied substantially among the different attained age-groups, especially in the youngest one (up to 19 years old). The analysis that was adjusted for screening and technological effects also indicated that in the high-exposure regions, thyroid cancer incidence rates at the age of diagnosis of 5-9, 10-14 and 15-19 years were significantly higher in those born in 1982-1986 compared to those born in 1987-1991, while in the low-exposure regions, no significant difference was observed. The observed probable excess of radiation-induced thyroid cancer cases in adults exposed to radioactive iodine from the Chernobyl accident, especially in females, may be due to the high power of the present study. However, it should be noted that our investigation was not essentially free from ecological biases.     

Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident

BackgroundThe excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of ¹³¹I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error.MethodsWe examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996–2004, who had direct thyroid ¹³¹I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied.ResultsThere was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy⁻ (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy⁻ (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy⁻ (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy⁻ (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053–0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2).ConclusionsIn summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.     

Thyroid cancer after diagnostic administration of iodine-131 in childhood.

Hahn, K., Schnell-Inderst, P., Grosche, B. and Holm, L-E. Thyroid Cancer after Diagnostic Administration of Iodine-131 in Childhood. Radiat. Res. 156, 61-70 (2001).To determine the carcinogenic effects of diagnostic amounts of (131)I on the juvenile thyroid gland, a multicenter retrospective cohort study was conducted on 4,973 subjects who either had been referred for diagnostic tests using uptake of (131)I (n = 2,262) or had had a diagnostic procedure on the thyroid without (131)I (n = 2,711) before the age of 18 years. Follow-up examinations were conducted after a mean period of 20 years after the first examination in 35% of the exposed subjects (n = 789) and in 41% of the nonexposed subjects (n = 1,118). Iodine-131 dosimetry of the thyroid was carried out according to ICRP Report No 53, and the median thyroid dose was 1.0 Gy. In the exposed group, two thyroid cancers were found during 16,500 person-years, compared to three cancers in the nonexposed group during 21,000 person-years. The relative risk for the exposed group was 0.86 (95% CI: 0.14-5.13). The study did not demonstrate an increased risk for thyroid cancer after administration of (131)I in childhood.     

食盐加碘后甲状腺摄131I 率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I 率的变化及其与24 小时尿碘含量的相关性,探讨甲状腺摄131I 率与 碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I 率的变化,分析健康体检者甲状腺摄131I 率、晨 尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6 及24 小时甲状腺 摄131I 率均显著降低;健康体检者甲状腺摄131I 率与24 小时尿碘含量呈负相关（r=－0.7651, P<0.001）,晨尿碘浓度与24 小时尿碘 含量呈正相关（r=0.8231, P<0.001）,经肌酐校正的尿碘含量与24 小时尿碘含量呈正相关（r=0.9054, P<0.001）。结论：食盐加碘对甲 状腺摄131I 率有显著影响,应重新确立甲状腺摄131I 率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更 准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study

Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose-response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8-31.5). At thyroid radiation doses >20 Gy, a downturn in the dose-response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P = 0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.     

Nicotinamide increases thyroid radiosensitivity by stimulating nitric oxide synthase expression and the generation of organic peroxides.

Differentiated thyroid cancer and hyperthyroidism are treated with radioiodine. However, when the radioisotope dose exceeds certain limits, the patient must be hospitalized to avoid contact with people that would otherwise be exposed to radiation. It would be desirable to obtain a similar therapeutic effect using lower radioiodine doses. Radiosensitizers can be utilized for this purpose. Nicotinamide (NA) increases thyroid radiosensitivity to 131I in both normal and goitrous glands. NA causes a significant increase in thyroid blood flow, which would increase tissue oxygenation and tissue damage via free radicals. Wistar rats were treated with either nicotinamide (NA), 131I or both. The expression of the three isoforms of nitric oxide synthase (NOS) in the thyroid (Western blot) and the activities of SOD, GPx, catalase and organic peroxides were determined. Treatment with NA or 131I increased the expression of eNOS and the generation of organic peroxides. When administered jointly, they showed a synergistic effect. No changes were observed in the other NOS isoforms or in the activities of catalase, glutathione peroxidase and superoxide dismutase. NA potentiates the effect of 131I by increasing eNOS, which would in turn stimulate NO production, increasing thyroid blood flow and tissue damage via organic peroxides.     

Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people.

The frequency of mutant T lymphocytes defective in T-cell receptor gene (alpha or beta) expression was measured using the 2-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of greater than or equal to 1.5 Gy) and 125 of whom were distally exposed (DS86 dose of less than 0.005 Gy), showed that the mutant frequency was significantly higher in males than in females. No significant dose effects were observed. In contrast, a significant increase of mutant frequency was observed for 6 patients treated with Thorotrast, a contrast medium containing thorium-232 formerly used for radioligands. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for measurement of recent exposures to genotoxic agents.     

食盐加碘后甲状腺摄 ~（131）I率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I率的变化及其与24小时尿碘含量的相关性,探讨甲状腺摄131I率与碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I率的变化,分析健康体检者甲状腺摄131I率、晨尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6及24小时甲状腺摄131I率均显著降低;健康体检者甲状腺摄131I率与24小时尿碘含量呈负相关（r=-0.7651,P〈0.001）,晨尿碘浓度与24小时尿碘含量呈正相关（r=0.8231,P〈0.001）,经肌酐校正的尿碘含量与24小时尿碘含量呈正相关（r=0.9054,P〈0.001）。结论：食盐加碘对甲状腺摄131I率有显著影响,应重新确立甲状腺摄131I率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。