Valentina Drozd

The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl

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.

Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma.

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.

Accuracy of Three-Dimensional Ultrasound for Thyroid Volume Measurement in Children and Adolescents

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.

Three-Dimensional Ultrasonography for Volume Measurement of Thyroid Nodules in Children

Objective. The aim of this study was to compare the accuracy of thyroid nodule volume measurements performed by 2‐ and 3‐dimensional ultrasonography and to evaluate the dependence of volume measurement results on nodule size and echographic characteristics. Methods. Results of multiple 2‐ and 3‐dimensional ultrasonographic volume measurements of thyroid nodules in 102 children with different variants of thyroid nodular disease were reviewed retrospectively. The standardized difference, within‐observer variability, and repeatability were estimated for both 2‐ and 3‐dimensional ultrasonography. The mean age of the patients ± SD in the examined group was 14.9 ± 2.8 years; the mean volume of thyroid nodules was 0.78 ± 0.13 mL. Results. The SD of the normalized difference for 3‐dimensional ultrasonography (2.8%) showed the clear superiority of its accuracy over 2‐dimensional ultrasonography (15.9%; F test, P < .01). Intraobserver variability and repeatability for both examined methods had significant dependence on the nodule outline. For 2‐dimensional ultrasonography, the intraobserver variability increased from 14.0% in nodules with a regular outline to 24.5% in those with an irregular outline (P < .001), and for 3‐dimensional ultrasonography, it increased from 5.1% to 9.3% (P < .001). Intraobserver repeatability dropped from 85.4% in regular nodules to 74.6% in irregular nodules (P < .001) for 2‐dimensional ultrasonography and from 94.7% to 90.4% (P < .001) for 3‐dimensional ultrasonography. Conclusions. Volume measurements by 3‐dimensional ultrasonography are more accurate, showing lower intraobserver variability and higher repeatability, than those made by 2‐dimensional ultrasonography with less dependence on nodule size and echographic characteristics.

Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl

PurposeThe 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 (131I).MethodsA total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with 131I were assessed. A group of 29 patients without lung metastases and prior 131I 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 (

The usual ultrasonographic features of thyroid cancer are less frequent in small tumors that develop after a long latent period after the Chernobyl radiation release accident.

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Results of radioactive iodine treatment in children from Belarus with advanced stages of thyroid cancer after the Chernobyl accident

O2), oxygen saturation and alveolar-arterial difference in oxygen partial pressure (ΔaaO2).ResultsFive 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