<prompt> Smoking is a risk factors for all the carcinoma exceptOralBronchialBladderThyroid  <response>: Ref Robbins 9e 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-3KAKT 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. 