Polymorphisms in the Initiators of RET (Rearranged during Transfection) Signaling Pathway and Susceptibility to Sporadic Medullary Thyroid Carcinoma

Context: Medullary thyroid carcinoma (MTC) is a characteristic tumor occurring in individuals with multiple endocrine neoplasia type 2 who carry germ-line mutations in RET (rearranged during transfection). However, most MTC occur in individuals without a family history. Objectives: The objective of this study was to explore the possibility that susceptibility in these cases results from low penetrance alleles of RET, its coreceptors, and ligands. Design: We carried out an association study in 135 sporadic MTC (sMTC) patients and 533 controls from the United Kingdom population. Results and Conclusions: We analyzed 33 polymorphisms in all nine genes involved in the glial cell line-derived neurotropic factor receptor-α (GFRα)-RET complex. This is the first association study in which all genes involved in this complex have been investigated for susceptibility to sMTC. We did not find any association between single nucleotide polymorphisms in the exonic regions of the GFRα2, GFRα3, GFRα4, glial cell line-deriv...