Objective
The objectives of this proposal are to delineate the pathological and molecular biological changes that characterise the tumours arising in children from the most heavily exposed areas of Belarus and the Ukraine, to correlate the morphology with the molecular biology, and then to correlate the relative frequency of both morphological and molecular biological changes with place of residence at the time of the Chernobyl disaster, and reconstructed dose levels where these are reliable. Establishing a link between the morphological type and the molecular biological changes with radiation exposure closer to Chernobyl will then allow assessment of the relevance of possible small increases in countries exposed to lower levels of fallout, a clearer link between exposure and risk, and the continuation of that risk. It will also allow an assessment of the role of shortlived isotopes, as these become progressively less important as compared to 131I in the more distant areas which were reached by fallout at a later time than the areas close to Chernobyl. It is therefore expected that this work will enable us to answer in whole or in part the following questions:
(1) Does the increase in thyroid cancer observed in children between 4 and 8 ye after exposure to fallout from the Chernobyl accident continue, and does it inv a particular cohort giving tumours in older patients with the passage of time?
(2) Is the association of a particular pattern of morphology with exposure to fallout confirmed, and does this association hold for older patients?
(3) Is there a specific pattern of growth factor or oncogene involvement in presumed radiation induced thyroid carcinomas, and does this alter with increas time?
(4) Is there any evidence that the number and relative frequency of carcinomas the morphology of radiation induced tumour is influenced by the relative exposure to short and long lived isotopes of iodide?
We intend to use a variety of techniques to address these questions, morphologi analysis, growth factor and oncogene localisation on formalin fixed paraffin embbeded sections from pathological material obtained from centres in the CIS, well as conventional molecular biological techniques to define the presence of and the type of mutation or translocation in oncogenes known or suspected to be involved in human thyroid carcinogenesis. We will compare these results with tu from age and sex matched controls from non irradiated populations and with thyr tumours induced by radiation in transgenic mice which show thyroid specific oncogene expression.
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Programme(s)
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
CB2 2QQ Cambridge
United Kingdom
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