Measures of thyroid function among Belarusian children and adolescents exposed to iodine-131 from the accident at the Chernobyl nuclear plant.
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ABSTRACT: Background
Thyroid dysfunction after exposure to low or moderate doses of radioactive iodine-131 (131I) at a young age is a public health concern. However, quantitative data are sparse concerning 131I-related risk of these common diseases.Objective
Our goal was to assess the prevalence of thyroid dysfunction in association with 131I exposure during childhood (≤ 18 years) due to fallout from the Chernobyl accident.Methods
We conducted a cross-sectional analysis of hypothyroidism, hyperthyroidism, autoimmune thyroiditis (AIT), serum concentrations of thyroid-stimulating hormone (TSH), and autoantibodies to thyroperoxidase (ATPO) in relation to measurement-based 131I dose estimates in a Belarusian cohort of 10,827 individuals screened for various thyroid diseases.Results
Mean age at exposure (± SD) was 8.2 ± 5.0 years. Mean (median) estimated 131I thyroid dose was 0.54 (0.23) Gy (range, 0.001-26.6 Gy). We found significant positive associations of 131I dose with hypothyroidism (mainly subclinical and antibody-negative) and serum TSH concentration. The excess odds ratio per 1 Gy for hypothyroidism was 0.34 (95% CI: 0.15, 0.62) and varied significantly by age at exposure and at examination, presence of goiter, and urban/rural residency. We found no evidence of positive associations with antibody-positive hypothyroidism, hyperthyroidism, AIT, or elevated ATPO.Conclusions
The association between 131I dose and hypothyroidism in the Belarusian cohort is consistent with that previously reported for a Ukrainian cohort and strengthens evidence of the effect of environmental 131I exposure during childhood on hypothyroidism, but not other thyroid outcomes.
SUBMITTER: Ostroumova E
PROVIDER: S-EPMC3701991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The U.S. National Cancer Institute, in collaboration with the Belarusian Ministry of Health, is conducting a study of thyroid cancer and other thyroid diseases in a cohort of about 12,000 persons who were exposed to fallout from the Chernobyl accident in April 1986. The study subjects were 18 years old or younger at the time of exposure and resided in Belarus in the most contaminated areas of the Gomel and Mogilev Oblasts, as well as in the city of Minsk. All cohort members had at least one direct thyroid measurement made in April-June 1986. Individual data on residential history, consumption of milk, milk products and leafy vegetables as well as administration of stable iodine were collected for all cohort members by means of personal interviews conducted between 1996 and 2007. Based on the estimated (131)I activities in the thyroids, which were derived from the direct thyroid measurements, and on the responses to the questionnaires, individual thyroid doses from intakes of (131)I were reconstructed for all cohort members. In addition, radiation doses to the thyroid were estimated for the following minor exposure pathways: (a) intake of short-lived (132)I, (133)I and (132)Te by inhalation and ingestion; (b) external irradiation from radionuclides deposited on the ground; and (c) ingestion intake of (134)Cs and (137)Cs. Intake of (131)I was the major pathway for thyroid exposure; its mean contribution to the thyroid dose was 92%. The thyroid doses from (131)I intakes varied from 0.5 mGy to almost 33 Gy; the mean was estimated to be 0.58 Gy, while the median was 0.23 Gy. The reconstructed doses are being used to evaluate the risk of thyroid cancer and other thyroid diseases in the cohort.
| S-EPMC3682838 | biostudies-literature
Project description:The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N) on 64 whole genome microarrays (Agilent, 4×44 K). Associations of differential gene expression (log(2)(T/N)) with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N). The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493) were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.
| S-EPMC3405097 | biostudies-literature
Project description:Background. The Chernobyl Nuclear Power Plant (CNPP) accident exposed a large number of inhabitants to internal (131)I radiation. The associations between internal (131)I exposure and thyroid autoimmunity and benign thyroid diseases remain controversial in the population living in the contaminated area around the CNNP. In this study, we evaluate the association of (131)I with benign thyroid diseases. Methods. We compared the prevalence of Anti-Thyroid Autoantibodies (ATAs), thyroid function, and prevalence of thyroid ultrasound finding outcomes in 300 residents of the contaminated area of Ukraine who were 0-5 years of age at the time of the CNPP accident (group 1) and 300 sex-matched residents who were born after the accident (group 2). Results. We did not find any differences of the prevalence of Antithyroglobulin Antibodies (TGAb) positive, Antithyroid Peroxidase Antibodies (TPOAb) positive, and TGAb and/or TPOAb positive between the study groups. (11.7% vs 10.3%; p = 0.602, 17.3% vs 13.0%; p = 0.136, 21.0% vs 17.3%; p = 0.254, respectively); after adjusting for age and sex, the prevalence was not associated with the (131)I exposure status in the study groups. The prevalence of subclinical and overt hypothyroidism cases was not significantly different (p = 0.093 and p = 0.320) in the two groups, nor was the prevalence of goiter (p = 0.482). On the other hand, the prevalence of nodules was significantly higher in group 1 (p = 0.003), though not significantly so after adjustment for age and sex. Discussion. Working 26-27 years after the CNNP accident, we found no increased prevalence of ATAs or benign thyroid diseases in young adults exposed to (131)I fallout during early childhood in the contaminated area of Ukraine. Long-term follow-up is needed to clarify the effects of radiation exposure on autoimmunity reaction in the thyroid.
| S-EPMC4806629 | biostudies-literature
Project description:BackgroundA strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis.MethodsWe evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR.ResultsExpression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue.ConclusionThe multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.
| S-EPMC3798970 | biostudies-literature
Project description:The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy(-1) (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy(-1) (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy(-1) (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p = 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment.
| S-EPMC3906013 | biostudies-literature
Project description:Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL, and CALR genes; however, 10%-15% of cases are triple negative (TN). A previous study showed lower rate of JAK2 V617F in primary myelofibrosis patients exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To examine distinct driver mutations, we enrolled 281 Ukrainian IR-exposed and unexposed MPN patients. Genomic DNA was obtained from peripheral blood leukocytes. JAK2 V617F, MPL W515, types 1- and 2-like CALR mutations were identified by Sanger Sequencing and real time polymerase chain reaction. Chromosomal alterations were assessed by oligo-SNP microarray platform. Additional genetic variants were identified by whole exome and targeted sequencing. Statistical significance was evaluated by Fisher's exact test and Wilcoxon's rank sum test (R, version 3.4.2). IR-exposed MPN patients exhibited a different genetic profile vs unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%, P = .0077), higher rate of type 1-like CALR mutation (12.2% vs 3.1%, P = .0056), higher rate of TN cases (27.8% vs 16.2%, P = .0366), higher rate of potentially pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = .0242). Furthermore, we identified several potential drivers specific to IR-exposed TN MPN patients: ATM p.S1691R with copy-neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q and SUZ12 p.V71 M at 17q with copy number loss. Thus, IR-exposed MPN patients represent a group with distinct genomic characteristics worthy of further study.
| S-EPMC6371805 | biostudies-literature
Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ≥ 1.5 and adjusted p-value ≤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp.
2016-06-30 | GSE66623 | GEO
Project description:Prenatal exposure to external radiation has been linked to growth retardation among atomic bomb survivors in adolescence. It is unclear from previous studies whether in utero exposure to internal radiation such as iodine-131 (I-131), which concentrates in the thyroid gland, has an effect on physical growth. We examined the associations between estimated thyroid gland dose from prenatal exposure to I-131 and self-reported height and weight in a cohort of 2,460 individuals exposed to radioactive fallout from the 1986 Chernobyl nuclear accident [mean I-131 dose = 72 (mGy)] and screened for thyroid diseases in adolescence. Using multivariable linear regression models, we estimated the mean differences in height, weight and body mass index (BMI) per unit increase in dose (100 mGy) in models adjusted for gender, age at examination, type of residence (rural/urban) and presence of thyroid disease diagnosed at screening. All of the adjustment factors as well as the trimester of exposure were evaluated as potential modifiers of the dose response. Overall, no significant dose response was found for height (P = 0.29), weight (P = 0.14) or BMI (P = 0.16). We found significant modification of the dose response for weight and BMI by presence/absence of thyroid disease (P = 0.02 and P = 0.03, respectively), but not for other factors. In individuals without thyroid disease (n = 1,856), there was a weak, significant association between I-131 thyroid dose and higher weight (210 g per 100 mGy, P = 0.02) or BMI (70 g/m² per 100 mGy, P = 0.02) that depended on individuals (n = 52) exposed to ?500 mGy. In individuals with thyroid disease (n = 579, 67.4% with simple diffuse goiter) no significant association with I-131 for weight (P = 0.14) or BMI (P = 0.14) was found. These results do not support the hypothesis that in utero exposure to I-131 at levels experienced by a majority of study subjects may be associated with meaningful differences in adolescent anthropometry. However, additional studies are needed to clarify whether in utero exposure to I-131 at levels > = 500 mGy may be associated with increases in weight/BMI and to evaluate the confounding or modifying role of thyroid disease, past iodine deficiency, maternal and prenatal/postnatal factors.
| S-EPMC4068270 | biostudies-literature
Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ⥠1.5 and adjusted p-value ⤠0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp. Total RNA was isolated from fresh-frozen individual thyroid tissue samples (Sprague Dawley rats). Each sample was run once. Four rats received the same treatment. Control samples (from non-irradiated rats) are included.
2016-06-30 | E-GEOD-66623 | biostudies-arrayexpress
Project description:The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood 131I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.
| S-EPMC9022889 | biostudies-literature