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1.
J Neural Transm (Vienna) ; 127(11): 1455-1466, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33034734

RESUMO

The thyroid gland is among the organs at the greatest risk of cancer from ionizing radiation. Epidemiological evidence from survivors of radiation therapy, atomic bombing, and the Chernobyl reactor accident, clearly shows that radiation exposure in childhood can cause thyroid cancer and benign thyroid nodules. Radiation exposure also may induce hypothyroidism and autoimmune reactions against the thyroid, but these effects are less well-documented. The literature includes only a few, methodologically weak animal studies regarding genetic/molecular mechanisms underlying hypothyroidism and thyroid autoimmunity after radiation exposure. Rather, evidence about radiation-induced hypothyroidism and thyroid autoimmunity derives mainly from follow-up studies in patients treated with external beam radiotherapy (EBRT) or iodine-131, and from epidemiological studies in the atomic bombing or nuclear accident survivors. Historically, hypothyroidism after external irradiation of the thyroid in adulthood was considered not to develop below a 10-20 Gy dose threshold. Newer data suggest a 10 Gy threshold after EBRT. By contrast, data from patients after iodine-131 "internal radiation therapy" of Graves´ disease indicate that hypothyroidism rarely occurs below thyroid doses of 50 Gy. Studies in children affected by the Chernobyl accident indicate that the dose threshold for hypothyroidism may be considerably lower, 3-5 Gy, aligning with observations in A-bomb survivors exposed as children. The reasons for these dose differences in radiosensitivity are not fully understood. Other important questions about the development of hypothyroidism after radiation exposure e.g., in utero, about the interaction between autoimmunity and hypofunction, and about the different effects of internal and external irradiation still must be answered.


Assuntos
Hipotireoidismo , Neoplasias da Glândula Tireoide , Adulto , Relação Dose-Resposta à Radiação , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Radioisótopos do Iodo
3.
Endocr J ; 62(2): 173-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25374130

RESUMO

Long-term management of patients with differentiated thyroid cancer (DTC) commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal health. Experience with female patients treated for DTC at a young age and who were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very limited to date. This cross-sectional study set out to investigate effects of Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and followed-up for an average of 10 years. BMD was found to be significantly higher in patients receiving Calcium-D3 medication than in patients not taking supplements. The level of ionized calcium was the strongest factor determining lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy ending in childbirth and HDL-cholesterol were associated with a weak adverse effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect BMD in women treated for DTC at young age, at least after 10 years of follow-up.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Cálcio da Dieta/uso terapêutico , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/efeitos da radiação , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/epidemiologia , Reabsorção Óssea/etiologia , Acidente Nuclear de Chernobyl , Terapia Combinada/efeitos adversos , Estudos Transversais , Feminino , Seguimentos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipoparatireoidismo/tratamento farmacológico , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Incidência , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/radioterapia , Neoplasias Induzidas por Radiação/cirurgia , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , República de Belarus/epidemiologia , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tiroxina/efeitos adversos , Tiroxina/uso terapêutico
4.
Hum Mol Genet ; 19(12): 2516-23, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20350937

RESUMO

Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology-specific genetic determinants in radiation-related PTC.


Assuntos
Carcinoma Papilar/genética , Acidente Nuclear de Chernobyl , Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença , Neoplasias Induzidas por Radiação/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Feminino , Loci Gênicos , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Adulto Jovem
5.
Eur J Nucl Med Mol Imaging ; 38(4): 651-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21113590

RESUMO

PURPOSE: The aim of this study is to report on a collective of 20 children from Belarus who had developed papillary thyroid carcinoma with pulmonary metastases after the Chernobyl disaster. In all children fractionated radioiodine therapy (RIT) was ceased before achieving complete remission due to a lack of further effects of (131)I therapy and an increased risk of pulmonary fibrosis. METHODS: The 20 children (12 girls) were treated with (131)I using 50 MBq/kg body weight for thyroid remnant ablation and 100 MBq/kg for further therapy in intervals of 5-12 months. After five to six courses and a cumulative activity of about 24 GBq (131)I no further RIT was conducted; the median thyroglobulin (TG) was 56 µg/l at this time. All patients were followed for at least 10 years after cessation of RIT using diagnostic whole-body scintigraphy, CT of the chest, lung function testing and stimulated TG measurements every 1-3 years. RESULTS: During follow-up after the last RIT a continuous decline of values for TG levels of ∼35% per year was observed between individual visits. The median Tg level at the time of cessation of (131)I therapy was 56 µg/l; however, at the last visit 16 of 20 patients had a TG level ≤10 µg/l (median 2.4 µg/l). Neither on diagnostic radioiodine whole-body scan nor on CT was progression of lung metastases observed. No significant pulmonary fibrosis developed. CONCLUSION: In spite of incomplete remission of thyroid cancer at cessation of RIT, a continuing spontaneous decline of TG and clinically stable partial remissions were observed in this collective of children. Therefore, if RIT does not show further effects, the administration of further courses should be handled restrictively.


Assuntos
Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Adolescente , Carcinoma , Carcinoma Papilar , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Recidiva , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia
6.
Eur J Nucl Med Mol Imaging ; 38(9): 1683-90, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21626048

RESUMO

PURPOSE: The objective of this project was to systematically determine the prevalence and consequences of pulmonary fibrosis in youth with thyroid carcinoma and lung metastases from Belarus who were treated with radioiodine ((131)I). METHODS: A total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with (131)I were assessed. A group of 29 patients without lung metastases and prior (131)I treatment served as controls. The assessments included a CT scan of the lungs, extensive pulmonary function testing and an incremental cycle test to volitional fatigue with measurements of oxygen uptake (VO(2)), oxygen saturation and alveolar-arterial difference in oxygen partial pressure (ΔaaO(2)). RESULTS: Five patients with lung metastases showed advanced pulmonary fibrosis on CT scans and also had poorer lung functions compared with the 62 patients with none or minor signs of fibrosis and the 29 controls. Furthermore, these five patients showed lower peak VO(2), lower oxygen saturation at peak exercise and higher exercise ΔaaO(2). They were younger at the time of cancer diagnosis and had received chemotherapy more frequently than youth with pulmonary metastases who did not develop fibrosis. One of the five patients subsequently died from pulmonary fibrosis. CONCLUSION: Following the Chernobyl catastrophe, about 7% of children treated with radioiodine for thyroid carcinoma and lung metastases displayed pulmonary fibrosis which was associated with functional impairments. Based on the characteristics of affected individuals, the number of radioiodine courses may have to be limited, especially in young children, and chemotherapy should be avoided.


Assuntos
Acidente Nuclear de Chernobyl , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/etiologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Criança , Teste de Esforço , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Medidas de Volume Pulmonar , Masculino , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/fisiopatologia , República de Belarus/epidemiologia , Fatores de Risco , Tomografia Computadorizada por Raios X
7.
Eur J Nucl Med Mol Imaging ; 38(7): 1296-302, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21461735

RESUMO

PURPOSE: Differentiated thyroid carcinoma (DTC) in children and young adults is rare but often aggressive and in an advanced stage at diagnosis. In a cohort of young Belarusian patients with advanced DTC after Chernobyl we retrospectively studied parameters influencing the success of the postoperative (131)I therapy. METHODS: Included in the study were 136 patients (83 female, 53 male; median age 14.3 years, range 9.4-22.8 years) who had had total thyroidectomy in Belarus and subsequent (131)I therapy and follow-up in Germany. Of the 136 patients, 34 were classified as M1 and 102 as M0 (N0 1, N1 101). The median weight-adjusted (131)I activity administered after thyroid hormone withdrawal was 52 MBq/kg (range 24-74 MBq/kg). TNM stage, gender, administered activity, whole-body residence time and blood dose during ablation, Tg and TSH levels, date, and age at time of treatment were tested for their effect on the rate of complete remission (CR). CR was defined as a negative scan and a stimulated Tg level of <1 ng/ml at follow-up. RESULTS: CR was observed in 1 of 34 M1 and in 51 of 102 M0 patients after the first treatment. Multivariate analysis in the M0 group identified the Tg level (P < 0.0001 for log(Tg)) and the radiation absorbed dose to the blood (P < 0.001) as independent determinants; all other parameters were unimportant (P > 0.3). The regression model was able to correctly predict CR in 82 of 102 patients (80.4%). CONCLUSION: In children and young adults with advanced DTC, the rate of CR after postoperative (131)I therapy is dependent on the preablative Tg level and the radiation absorbed dose to the blood. Though the present results must be confirmed in a prospective study, they imply that preablative dosimetry may improve rates of CR.


Assuntos
Acidente Nuclear de Chernobyl , Neoplasias Induzidas por Radiação/sangue , Neoplasias Induzidas por Radiação/radioterapia , Doses de Radiação , Tireoglobulina/metabolismo , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/metabolismo , Neoplasias Induzidas por Radiação/patologia , Período Pós-Operatório , República de Belarus , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-33810323

RESUMO

The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4-5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.


Assuntos
Acidente Nuclear de Chernobyl , Acidente Nuclear de Fukushima , Neoplasias Induzidas por Radiação , Neoplasias da Glândula Tireoide , Adolescente , Criança , Humanos , Incidência , Japão/epidemiologia , Masculino , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia
9.
J Radiat Res ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34536956

RESUMO

The Chernobyl accident on 26 April 1986 led to a sharp increase in thyroid cancer (TC) incidence in the individuals exposed to radiation in childhood. The major risk factor for TC was exposure to Iodine-131 (131I). Here, we estimated the thyroid doses due to 131I intake for 2041 participants of the genome-wide association study of TC in Belarusian people exposed to radioactive fallout from the Chernobyl accident. The following parameter-values specially developed in this study were used to estimate individual thyroid doses: (i) scaling factors for adjustment of the model-based doses, (ii) age and gender diet to characterize 131I intake, and (iii) area-, age- and gender-specific S-values for the thyroid gland per 131I decay in the thyroid. The most reliable doses were calculated for 103 people with measured 131I thyroid activity (the arithmetic mean of 1.2 Gy, median 0.52 Gy), and 275 individuals with detailed residential history and dietary data (the arithmetic mean of 0.41 Gy, median 0.24 Gy). The arithmetic mean of thyroid doses among all study participants was 0.23 Gy (median 0.082 Gy); the highest individual dose was 9.0 Gy. Special attention was paid to the reliability and validity of the obtained estimates, in particular for the individuals without 131I thyroid activity measurements and individual data on residential history and diet, by comparing those with the doses from other post-Chernobyl epidemiological studies. Overall, the doses estimated in the current study were in reasonable agreement with previously reported thyroid doses. These doses will be used in the genome-wide association study of TC in people exposed in Belarus to 131I after the Chernobyl accident.

10.
Front Endocrinol (Lausanne) ; 11: 567385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193085

RESUMO

Objective: This single-center, observational case-control feasibility study sought to test key elements of a protocol for an eventual long-term international observational case-control study of a larger patient cohort, to evaluate the risk of breast cancer as a second primary malignancy in females with differentiated thyroid cancer (DTC) given radioiodine therapy (RAI) during childhood or adolescence. Patients: Females developing DTC after the Chernobyl accident in Belarus and ≤19 years old at the time of thyroid surgery were enrolled: patients given RAI (n = 111) and controls of similar age not given RAI (n = 90). Results: One case of breast cancer was newly diagnosed among the RAI patients, but none in controls. Patients given RAI significantly less frequently needed 2nd surgeries than did controls (23%, 26/111 vs. 39%, 35/90, P < 0.05); the main indication for such procedures usually is suspicion of local recurrence. RAI patients appeared to have had more frequent reproductive difficulties than did controls: 78% (87/111) of the former vs. 93% (84/90) of the latter had a history of pregnancy (P < 0.01), and the mean number of pregnancies was 1.5 ± 1.2 in RAI patients vs. 1.9±1.1 in controls (P < 0.05). Most notably, infertility was observed in 23% (26/111) of RAI patients vs. 4% (4/90) of controls (P < 0.01). In conclusion, a international observational case-control study on breast cancer after DTC in patients given RAI vs. not given RAI appears to be feasible. Additional research and everyday clinical attention should be devoted to reproductive function after RAI in young females.


Assuntos
Neoplasias da Mama/epidemiologia , Acidente Nuclear de Chernobyl , Infertilidade Feminina/epidemiologia , Radioisótopos do Iodo/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Internacionalidade , Radioisótopos do Iodo/administração & dosagem , Neoplasias Induzidas por Radiação/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/radioterapia
11.
Artigo em Inglês | MEDLINE | ID: mdl-32754115

RESUMO

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case-control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial "misdiagnosis."


Assuntos
Neoplasias da Mama/induzido quimicamente , Radioisótopos do Iodo/efeitos adversos , Neoplasias Induzidas por Radiação/induzido quimicamente , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Induzidas por Radiação/epidemiologia , Sistema de Registros , Neoplasias da Glândula Tireoide/epidemiologia , Resultado do Tratamento
12.
Endocr Relat Cancer ; 16(2): 491-503, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19286843

RESUMO

Papillary thyroid carcinoma (PTC) etiologically occurs as a radiation-induced or sporadic malignancy. Genetic factors contributing to the susceptibility to either form remain unknown. In this retrospective case-control study, we evaluated possible associations between single-nucleotide polymorphisms (SNPs) in the candidate DNA damage response genes (ATM, XRCC1, TP53, XRCC3, MTF1) and risk of radiation-induced and sporadic PTC. A total of 255 PTC cases (123 Chernobyl radiation-induced and 132 sporadic, all in Caucasians) and 596 healthy controls (198 residents of Chernobyl areas and 398 subjects without history of radiation exposure, all Caucasians) were genotyped. The risk of PTC and SNPs interactions with radiation exposure were assessed by logistic regressions. The ATM G5557A and XRCC1 Arg399Gln polymorphisms, regardless of radiation exposure, associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.45-0.86 and OR = 0.70, 95% CI 0.59-0.93 respectively). The ATM IVS22-77 T > C and TP53 Arg72Pro SNPs interacted with radiation (P = 0.04 and P = 0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (OR = 1.84, 95% CI 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (OR = 1.80, 95% CI 1.06-2.36). In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (OR = 2.10, 95% CI 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (OR = 3.32, 95% CI 1.57-6.99). The results indicate that polymorphisms of DNA damage response genes may be potential risk modifiers of ionizing radiation-induced or sporadic PTCs.


Assuntos
Carcinoma Papilar/genética , Dano ao DNA/genética , Marcadores Genéticos/genética , Neoplasias Induzidas por Radiação/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Proteínas Mutadas de Ataxia Telangiectasia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Radiação Ionizante , Estudos Retrospectivos , Fatores de Risco , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X , Adulto Jovem , Fator MTF-1 de Transcrição
13.
Eur Thyroid J ; 7(2): 67-74, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29594057

RESUMO

In recent decades, differentiated thyroid cancer (DTC) incidence has been increasing worldwide. The important contributions to this phenomenon of "overdiagnosis" driven by wider use of improved ultrasound systems are amply documented, notwithstanding the "real" carcinogenic effects of ionizing radiation, e.g., from the Chernobyl accident or health care interventions. Less well understood is the role of nitrates - as environmental pollutants, in diet, and in medication - in thyroid carcinogenesis. Increasing exposure to nitrates is associated with rising incidence of esophageal, stomach, bladder, and colon cancers. Recent data suggest that in agricultural areas with higher mean nitrate levels in groundwater, DTC risk is also elevated. Our work in Belarus after Chernobyl has shown that children in districts with high nitrate concentrations in drinking water had significantly higher thyroid cancer incidence after irradiation than did their counterparts in areas with lower nitrate concentrations. Notwithstanding thyroid shielding, increasing use of computed tomography and dental X-rays heightens radiation exposure of the salivary glands in the general population, especially in children and adolescents. When nitrate intake is increased, salivary gland irradiation may potentially result in carcinogenic elevations in plasma nitric oxide concentrations. In conclusion, excess nitrate intake seems to be an independent risk factor for DTC. Additionally, we hypothesize from our data that high nitrate levels modulate the carcinogenic effect of radiation on the thyroid. Cohort studies, case-control studies, or both, are needed to quantify the effects of nitrates on DTC risk in the presence or absence of radiation exposure, e.g., that associated with diagnostic or therapeutic health care interventions.

14.
Endocr J ; 54(6): 839-47, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17938505

RESUMO

One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan.


Assuntos
Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Induzidas por Radiação/radioterapia , Segunda Neoplasia Primária/etiologia , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Segunda Neoplasia Primária/prevenção & controle , Medição de Risco , Tireotropina/farmacologia , Tiroxina/farmacologia
15.
Thyroid ; 27(2): 224-235, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27824288

RESUMO

BACKGROUND: Several functional single-nucleotide polymorphisms (SNPs) at the FOXE1 locus on chromosome 9q22.33 have been associated with the risk for papillary thyroid carcinoma (PTC). This study set out to elucidate whether their effects are independent, using genotyping results in populations of Asian and European descent. METHODS: SNPs rs965513 and rs1867277 and a polymorphic region determining the length of the FOXE1 polyalanine (poly-Ala) tract were genotyped in 501 patients with PTC and 748 healthy individuals from Japan, and in 660 patients and 820 population controls from Belarus. Functional analysis of transactivation activities of FOXE1 isoforms with varying number of alanine repeats was performed by a Dual-Luciferase® Assay. RESULTS: All three polymorphisms were significantly associated with PTC in both populations on univariate analysis. However, conditional analysis revealed independent effects of rs965513 and rs1867277 SNPs but not of the FOXE1 poly-Ala polymorphism. The independent effect of the lead rs965513 SNP was observed in both populations, while that of rs1867277 was only identified in the Japanese population, in which linkage disequilibrium between the three polymorphisms is markedly weaker. Despite the strong decrease in transcriptional activity with increasing FOXE1 poly-Ala tract length, no difference in transactivation potential of the FOXE1 poly-Ala isoforms could be seen after adjustment for the minimal promoter activity in the reporter vectors. Plasmids encoding FOXE1 isoforms of increasing poly-Ala tract length were also found to produce less FOXE1 protein after cell transfection. CONCLUSIONS: The functional variants rs965513 and rs1867277 independently contribute to genetic predisposition to PTC, while a contributing role of the FOXE1 poly-Ala polymorphism could not be confirmed.


Assuntos
Carcinoma Papilar/genética , Fatores de Transcrição Forkhead/genética , Peptídeos/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Povo Asiático/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , República de Belarus , Câncer Papilífero da Tireoide , População Branca/genética , Adulto Jovem
18.
Eur Endocrinol ; 12(2): 85-88, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29632593

RESUMO

Introduction: Recently, radiofrequency ablation (RFA) has been increasingly used for the treatment of thyroid nodules. However, immediate morphological changes associated with bipolar devices are poorly shown. Aims: To present the results of analysis of gross and microscopic alterations in human thyroid tissue induced by RFA delivered through the application of the original patented device. Materials and methods: In total, there were 37 surgically removed thyroid glands in females aged 32-67 at presentation: 16 nodules were follicular adenoma (labelled as 'parenchymal' solid benign nodules) and adenomatous colloid goitre was represented by 21 cases. The thyroid gland was routinely processed and the nodules were sliced into two parts - one was a subject for histological routine processing according to the principles that universally apply in surgical pathology, the other one was used for the RFA procedure. Results: No significant difference in size reduction between parenchymal and colloid nodules was revealed (p>0.1, t-test) straight after the treatment. In addition, RFA equally effectively induced necrosis in follicular adenoma and adenomatous colloid goitre (p>0.1, analysis of variance test). As expected, tumour size correlated with size reduction (the smaller the size of the nodule, the greater percentage of the nodule volume that was ablated): r=-0.48 (p<0.0001). Conclusion: The results make it possible to move from ex vivo experiments to clinical practice.

19.
PLoS One ; 10(9): e0137226, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26397978

RESUMO

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.


Assuntos
Compostos de Iodo/toxicidade , Radioisótopos do Iodo/toxicidade , Neoplasias Induzidas por Radiação/epidemiologia , Nitratos/toxicidade , Neoplasias da Glândula Tireoide/epidemiologia , Poluentes Radioativos da Água/toxicidade , Adolescente , Acidente Nuclear de Chernobyl , Criança , Pré-Escolar , Detecção Precoce de Câncer , Exposição Ambiental , Água Subterrânea/análise , Humanos , Incidência , Lactente , Recém-Nascido , Compostos de Iodo/análise , Radioisótopos do Iodo/análise , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Neoplasias Induzidas por Radiação/etiologia , Nitratos/análise , República de Belarus/epidemiologia , Fatores de Risco , Poluentes Radioativos do Solo/análise , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/etiologia , Ultrassonografia , Poluentes Radioativos da Água/análise
20.
Radiat Res ; 161(4): 481-92, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15038762

RESUMO

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.


Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Centrais Elétricas , Liberação Nociva de Radioativos , Doenças da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Recém-Nascido , Radioisótopos do Iodo , Masculino , Neoplasias Induzidas por Radiação/etiologia , Radiometria , Projetos de Pesquisa , Risco , Doenças da Glândula Tireoide/etiologia , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/etiologia , Fatores de Tempo , Ucrânia
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