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.

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.

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 singlenucleotide 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)Z0.69, 95% confidence interval (CI) 0.45-0.86 and ORZ0.70, 95% CI 0.59-0.93 respectively). The ATM IVS22-77 TOC and TP53 Arg72Pro SNPs interacted with radiation (PZ0.04 and PZ0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (ORZ1.84, 95% CI 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (ORZ1.80, 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 (ORZ2.10, 95% CI 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (ORZ3.32, 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.

Study findings indicate that US is most helpful in diagnosis of thyroid malignancy in thyroid nodules with diameter of 15 mm and smaller, with detection of irregular tumor outline, subcapsular location, and increased intranodular vascularization.

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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.

The aim of this study was to estimate accuracy, intraobserver variability, and repeatability of thyroid volume measurement by ultrasound using conventional two-dimensional ellipsoid model (2D US) and manual planimetry of three-dimensional images (3D US). The sonographic images of 47 children with thyroid nodular pathology who were referred for thyroid surgery in Belarus were evaluated prospectively. Two-dimensional images were acquired using the ultrasound scanner with 7.5-MHz linear probe. Three-dimensional data sets were created using three-dimensional system, FreeScan. For each patient thyroid volume was measured three times using both two- and three-dimensional methods. Results of volume estimation were then compared to the volume of thyroid gland determined after surgery. Standardized difference between thyroid volume estimated by ultrasound and surgery (mean +/- standard deviation (SD), %) for 3D and 2D US methods was 1.8 +/- 5.2% and 3.2 +/- 15.3%, respectively. The 3D US has lower intraobserver variability (3.4%) and higher repeatability (96.5%) than 2D US with 14.4% variability and 84.8% repeatability (p < 0.001). In conclusion, three-dimensional sonography allows accurate measurement of thyroid volume with low intraobserver variability and high repeatability.

Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.