The unique circumstances of this study were provided for by the legacy of the radioactive accident at Chernobyl Nuclear Power Plant in April 1986. Exposure to radioactive fallout led to a large increase in the incidence of papillary thyroid cancer (PTC), which was particularly pronounced in those who were children at the time of the accident. In normal circumstances, thyroid cancer is rare in children under the age of sixteen.
The Chernobyl Tissue Bank was established in 1998 to collect biological samples from those aged under 19 at the time of the accident who subsequently developed thyroid tumours and were resident in the areas of Ukraine and Russia contaminated by the radioactive iodine (131-I) fallout. Radioactive iodine 131-1 has a short half-life of seven days and quickly dissipates in the environment. The investigators were aware of the fact that the incidence of thyroid cancer had dropped down to normal occurrence rates in those children born 9 months after the Chernobyl accident. The continued collection of material by the Tissue Bank gave the investigators a unique opportunity to compare the samples gathered from children who experienced the Chernobyl accident with those born nine months after the incident whose thyroid cancers were unlikely to arise from exposure to 131-I.
The overall aim of the study was to compare the genetic mutations found in childhood thyroid cancer sufferers born before and after the accident - and assess the link to radiation exposure or patient age at diagnosis. Overall, 52 cases of PTC were studied, using tissue obtained from the Chernobyl Tissue Bank. These cases were split into four groups matched according to age, sex and place of residence. Two groups of 13 cases were from the areas of Ukraine most heavily contaminated with radioiodine - one group of 13 born before the accident and the other born after the 1st January 1997, and therefore spared exposure to radioiodine. The two other groups of 13 cases were from other areas of the Ukraine which were not exposed to significant radioiodine fallout - again consisting of one group of children with PTC born before the accident and one group born after 1st January 1987.
Molecular biology studies found no difference with respect to type or overall frequency of a particular genetic mutation, known as ret rearrangement, between any of the groups - despite the fact that ret rearrangement had been thought to be a potential marker of radiation exposure. This study therefore shows that, contrary to other reports in the literature, there is no association between ret rearrangement and radiation exposure. Rather, the study investigators believe that the real link between the patterns of molecular biological alterations observed post-Chernobyl in thyroid cancer might actually be related to the age of the patients under study, rather than radioiodine exposure. Only one child out of the 52 studied had a specific gene mutation, known as BRAF, which is typically present at higher levels in adult thyroid cancer sufferers. In contrast, 58% of adult thyroid cancer patients in the Ukraine show this mutation.
Overall, the insights provided by the study of Chernobyl children with thyroid cancer suggest that age at diagnosis of cancer should be taken into account before drawing conclusions about any link between the specific molecular biology of the cancer and radiation exposure - as this may actually have more significance.
Principle study investigator, Dr Gerry Thomas from the South West Wales Cancer Institute, UK commented, "The investigation of the molecular biology of thyroid cancer has shown that thyroid cancer in children is very different from that in adults. Attention is turning to the effect that age of the patient may have on other types of cancers. A better understanding of the biology of cancer will help us tailor treatments to different groups of patients in the future."
"Through the catastrophic accident at Chernobyl we have been able to glean further insight into the precise molecular link between radiation and cancer," stated Dr Thomas. "These study findings may have important implications for other ongoing investigations, such as those which are looking at the molecular nature of breast cancer in women who have previously undergone radiotherapy treatment for Hodgkin's disease. There is much debate about whether we in Europe should reconsider nuclear power as an option to meet our increasing energy demands. It is important that we take the opportunity to study the consequences of the Chernobyl accident in a proper scientific way, so that we can balance the risks against the benefits of different solutions to the energy problem in an educated way."
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2024 Head and neck cancer
The Chernobyl legacy: relationship between radiation exposure, RET rearrangement and BRAF mutation in childhood thyroid cancer
G. Thomas1, S. Jeremiah1, J. Bethel1, T. Bogdanova2, M. Tronko2, CTB Pathology Panel
1South West Wales Cancer Institute, Human Cancer Studies Group, Swansea, United Kingdom
2Institute of Endocrinology and Metabolism, Kiev, Ukraine
There was a large increase in the incidence of papillary thyroid cancer inj those areas of Ukraine exposed to radioactive fallout following the Chernobyl Nuclear Power Plant accident in April 1986. This increase was most pronounced in those who were children at the time of the accident. Thyroid cancer is usually very rare in children (aged under 16 at operation). 131-I has a relatively short physical half-life (7 days) and the rate of thyroid cancer has dropped back to background levels (of the order of 1 per million per year) in those who were born after 1st January 1987. The Chernobyl Tissue Bank (www.chernobyltissuebank.com) was established in 1998 to collect biological samples from those aged under 19 (i.e.born after 26th April 1967) at the time of the accident who subsequently developed thyroid tumours and were resident in the areas of Ukraine and Russia most highly contaminated by radioiodine in fallout. The continued collection of material has allowed us to collect samples from children from the same geographical area, but born more than 9 months after the accident, and whose thyroid cancer therefore is not the result of exposure to radioiodine. This is a unique situation that provides the opportunity to link molecular biology of cancer with a known environmental exposure to a mutagen.
The aim of this study was to investigate whether the frequency of ret rearrangement and BRAF mutation in papillary carcinoma of the thyroid (PTC) is related to exposure to radiation or the age of the patient at clinical diagnosis. RNA extracted from 52 cases of PTC were obtained from the Chernobyl Tissue Bank. The cases were divided into 4 groups matched on age, sex and place of residence. Two groups of 13 cases were from the areas of Ukraine most heavily contaminated with radioiodine, one group was born before the accident (1A), and the other born after 1/1/87 (1B) and therefore not exposed to radioiodine. Two other groups of 13 cases were from areas of Ukraine not exposed to significant fallout, one born before the accident (2A) and the other after 1/1/87 (2B). All patients were aged under 16 at the time of operation. The expression of ret was determined by RT-PCR for the extracellular and intracellular regions of c-ret  and PTC1 and 3 rearrangements were identified by rearrangement specific RT-PCR. For BRAF, mutation at position 1746 was identified by PCR followed by restriction enzyme digestion . There was no significant difference among the groups with respect to type or overall frequency of ret rearrangement. The most frequent rearrangement was PTC3, accounting for 16 of the 25 cases positive for ret rearrangement. Only one case (in group 2B) was positive for BRAF rearrangement. This study shows that contrary to other reports in the literature, there is no association of either ret rearrangement per se, or PTC3 rearrangement in particular, with radiation exposure. Thyroid cancer presenting in adults is typified by a higher frequency of BRAF mutation (58% in a series from Ukraine). We suggest that the pattern of molecular biological alterations observed in post Chernobyl thyroid cancer is related to the age of the patients under study, rather than to exposure to radioiodine. The Chernobyl experience suggests that age at diagnosis should be taken into account before conclusions are drawn regarding the relationship between molecular biology and radiation. This has implications for current studies in breast cancer following radiotherapy for Hodgkin's Disease.
 Powell et al., J Pathology (2005) 205: 558-564
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