Morphologic Characteristics of Chernobyl-Related Childhood Papillary Thyroid Carcinomas Are Independent of Radiation Exposure but Vary with Iodine Intake

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879486/

Thyroid. 2008 August; 18(8): 847–852.
doi: 10.1089/thy.2008.0039
PMCID: PMC2879486

Morphologic Characteristics of Chernobyl-Related Childhood Papillary Thyroid Carcinomas Are Independent of Radiation Exposure but Vary with Iodine Intake
E. Dillwyn Williams,corresponding author1 Alexander Abrosimov,2 Tatiana Bogdanova,3 Evgeny P. Demidchik,4 Masahiro Ito,5 Virginia LiVolsi,6 Evgeny Lushnikov,2 Juan Rosai,7 Mikola D. Tronko,3 Anatoly F. Tsyb,2 Sarah L. Vowler,8 and Geraldine A. Thomas9

1Strangeways Research Laboratory, Thyroid Carcinogenesis Research Unit, Worts Causeway, Cambridge, United Kingdom.
2MRRC RAMS, Obninsk, Russian Federation.
3Institute of Endocrinology and Metabolism, Kiev, Ukraine.
4Research Institute for Radiation Medicine and Clinical Endocrinology, Minsk, Belarus.
5Research Laboratory, National Nagasaki Medical Centre, Omura, Japan.
6Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Centre, Philadelphia, Pennsylvania.
7Departimento di Patologia, Instituto Nazionale Tumori, Milano, Italy.
8Department of Public Health and Primary Care, Centre for Applied Medical Statistics, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom.
9Imperial College Histopathology Department, Hammersmith Hospital, London, United Kingdom.

Copyright 2008, Mary Ann Liebert, Inc.

Abstract
Background

The Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency.

Methods

PTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan. The degree and type of differentiation, fibrosis, and invasion were quantified.
Results

There were no significant differences between PTCs from radiation-exposed children from Belarus, Ukraine, and the Russian Federation and PTCs from children from the same countries who were not exposed to radiation. Childhood PTCs from Japan were much more highly differentiated (p < 0.001), showed more papillary differentiation (p < 0.001) and were less invasive (p < 0.01) than “Chernobyl” tumors, while tumors from E&W generally showed intermediate levels of degree and type of differentiation and invasion. There was a marked difference between the sex ratios of children with PTCs who were radiation exposed and those who were not exposed (F:M exposed vs. unexposed 1.5:1 vs. 4.2:1; χ2 = 7.90, p ≤ 0.01005).
Conclusions

The aggressiveness and morphological features of Chernobyl childhood PTCs are not associated with radiation exposure. The differences found between tumors from the Chernobyl area, E&W, and Japan could be influenced by many factors. We speculate that dietary iodine levels may have wide implications in radiation-induced thyroid carcinogenesis, and that iodine deficiency could increase incidence, reduce latency, and influence tumor morphology and aggressiveness.

Introduction

A thyroid cancer endemic has occurred among those exposed to high levels of fallout from the Chernobyl nuclear power plant accident in 1986 (1–4). The tumors are dominantly papillary thyroid carcinomas (PTCs), and many early cases were aggressive and showed an unusual solid phenotype (5,6), uncommon in unexposed populations except young children (7). The great increase in papillary rather than follicular carcinoma, and the morphologic features have been linked to the molecular findings (8,9). The most common oncogenes involved in PTCs generally are rearrangements of tyrosine kinase (tk) genes, usually RET, less often TRK, and point mutations in BRAF (10–14). Radiation is the likely cause of the rearrangements; it preferentially induces double-strand DNA breaks and is less effective than other mutagens in inducing point mutations (15). PTCs with a solid (immature) morphology more often involve RET-PTC3 than tumors with a papillary (more differentiated) phenotype (8,9). A short latent period is linked to PTCs with a dominantly solid phenotype (16), and to a higher frequency of RET-PTC3 rearrangements (11). Mutations in BRAF are less frequent in childhood PTCs, exposed or unexposed, than in adult PTCs (17–19); it is not currently possible to separate the roles of age, latency, or mutagen. BRAF activation by rearrangement has occurred in short latency Chernobyl-related PTCs (20), supporting the relevance of radiation-induced double-strand breaks.

Early reports on Chernobyl-related thyroid carcinomas suggested that the solid morphology, aggressiveness, and high frequency of RET-PTC3 rearrangements were features of radiation-induced tumors (5,6,8). These features change with increasing latency and age (11,16,21). We set out to determine whether radiation-induced thyroid carcinomas differ in morphology and aggressiveness from non-radiation-induced tumors.

From “Discussion”: We have shown that radiation-induced childhood PTCs from countries around Chernobyl are morphologically indistinguishable from non-radiation-induced PTCs from the same areas. However, compared to two other countries these tumors are the least differentiated, show the least papillary differentiation, and are the most aggressive, while tumors from Japan are the most differentiated, show the most papillary differentiation, and are the least aggressive;
end quote of Abstract, Methods & Introduction & extract from “Discussion”

The idea that Fukushima Medical University could further whittle down its number of accepted "Fukushma Victims", (to date, none on the basis of the FMU incorrect declaration of a 4 year minimum latent period – the shortest latent period being months, the median being 4- 5 years, rendering "less than 4 fours" as an invalid reason for excluding victims from consideration as a "Fukushima victim".

See also Citation: Thyroid cancers after the Chernobyl accident;
Chernobyl accident; lessons learnt, an update. 2010.
Sir Dillwyn Williams
Cambridge
http://ec.europa.eu/energy/nuclear/radiation_protection/doc/scientific_seminar/2010/sir_d_williams_thyroid_cancers_after_chernobyl_accident.pdf


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