Smoking is a risk factors for all the carcinoma except

Ref Robbins 9/e p415 Genetic Factors. Distinct molecular events are involved in the pathogenesis of the four major variants of thyroid cancer. As stated, medullary carcinomas do not arise from the follicu- lar epithelium. Genetic alterations in the three follicular cell- derived malignancies are clustered along two oncogenic pathways--the mitogen-activated protein (MAP) kinase pathway and the phosphatidylinositol-3-kinase (PI-3K)/AKT pathway (Fig. 19-13). In normal cells, these pathways are transiently activated by binding of soluble growth factor ligands to the extracellular domain of receptor tyrosine kinases, which results in autophosphorylation of the cytoplas- mic domain of the receptor, permitting intracellular signal transduction. In thyroid carcinomas, as with many solid cancers (Chapter 5), gain-of-function mutations along components of these pathways lead to constitutive activation even in the absence of ligand, thus promoting carcinogenesis. Environmental Factors. The major risk factor predispos- ing to thyroid cancer is exposure to ionizing radiation, paicularly during the first 2 decades of life. In keeping with this finding, there was a marked increase in the incidence of papillary carcinomas among children exposed to ionizing radiation after the Chernobyl nuclear disaster in 1986. Defi- ciency of dietary iodine (and by extension, an association with goiter) is linked with a higher frequency of follicular carcinomas.