The results from these studies will provide a greater understanding of the mechanisms of radiation induced thyroid carcinogenesis, thereby identifying potential new avenues for therapeutic techniques.
The thyroid gland is particularly prone to autoimmune disease and it is known that exposure to radiation induces thyroiditis. The relationship between stimulation of the immune system in response to novel antigens associated with neoplasia and carcinogenesis is unclear. It was generally thought that stimulation of the immune response led to the production of a destructive infiltrate in the tumor, but recent evidence suggests that tumor lymphoid infiltrates may also produce factors which stimulate tumor cell growth. There has been a large increase in the numbers of thyroid carcinomas in children exposed to fallout from Chernobyl, in particular in papillary carcinomas. This morphological type of thyroid tumor is more commonly associated with thyroiditis than other types of thyroid tumor. No study has so far been made specifically of lymphoid infiltration in childhood thyroid cancer, nor of a comparison of tumors that are related to radiation exposure and those not associated with radiation exposure.
The objectives of this study are therefore to :
describe and quantify the tumor associated lymphoid infiltrate and correlate its frequency with the morphological type of tumor in patients from areas exposed to allout from Chernobyl and with age and sex matched patients with no known radiation exposure;
carry out analysis of the lymphocytic infiltrate within tumors to examine local production of factors known to be growth stimulatory to thyroid epithelial cells;
correlate the presence and type of lymphoid infiltrate with mutations in key thyroid oncogenes (ras, ret, and the TSH receptor).
These studies will require access to pathological material from children and adolescents with thyroid cancer from the areas exposed to fallout from Chernobyl, and the classification of the morphological types of tumor present. The study will be carried our on thyroid cancers occurring in patients born between 1976 and 1989 inclusive, so that it includes the recently identified most sensitive cohort, and also a group born after the accident, who would not have been exposed to radioiodine. It will also require access to thyroid tissue from non neoplastic thyroidectomies from exposed areas, and to thyroid cancers and non neoplastic thyroidectomies from unexposed patients.
Funding SchemeCSC - Cost-sharing contracts