Total thyroidectomy followed by radioiodine therapy is an optimal treatment strategy that makes it possible to achieve a cure in a vast majority of pediatric patients with differentiated thyroid carcinomas. Risk of recurrence is strongly associated with tumor stage, extent of surgery, the young patient's age, and presence of symptoms at diagnosis.
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.
Thyroid cancer in children is usually rare, but in the individuals exposed to radiation risk of disease increases considerably. After the Chernobyl accident in 1986, an over 10-fold maximal elevation in the incidence of thyroid cancer was registered about a decade later, cumulatively resulting in more than a thousand of newly diagnosed cases in children who lived in the territories of Belarus, Russia, and Ukraine affected by radioactive fallouts. Experience from the epidemic substantially promoted knowledge in clinical pediatric oncology, pathology and basic sciences. This article overviews epidemiology, clinical features, results of treatment and followup of childhood patients with radiation-induced Chernobyl thyroid cancer in comparison to sporadic cases diagnosed at present. In addition, we discuss general issues of pathology and molecular findings in childhood thyroid carcinomas.
RESUMOCâncer de Tiróide na Infância na Bielorússia, Rússia, e na Ucrânia, Após Chernobil e Atualmente. O câncer de tiróide é habitualmente raro em crianças, mas em indivíduos expostos a radiação o risco da doença aumenta consideravelmente. Cerca de uma década após o acidente de Chernobil, em 1986, foi registrado um aumento de mais de 10 vezes na incidência de câncer de tiróide, resultando cumulativamente em mais de mil novos casos diagnosticados em crianças que viviam nos territórios da Bielorrússia, Russia, e Ucrânia, afetadas pela chuva radioativa. A experiência com essa epidemia resultou em conhecimento substancial de oncologia pediátrica clínica, patologia e ciências básicas. Este artigo analisa a epidemiologia, os achados clínicos, os resultados do tratamento e a evolução de pacientes pediátricos com câncer de tiróide induzido pela radiação de Chernobil, em comparação com casos esporádicos diagnosticados atualmente. Adicionalmente, serão discutidos tópicos de patologia e achados moleculares no carcinoma de tiróide infantil.
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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