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 [1] 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 [1]. 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.
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