Medullary Thyroid Carcinoma Running Title: Association of RET, ARTN and GFRα1 with sMTC

*These authors contributed equally to this work Keywords: GFRα-RET complex, risk of developing MTC, Polymorphisms, haplotypes Copyright (C) 2005 by The Endocrine Society Context. Medullary thyroid carcinoma is a characteristic tumour occurring in individuals with multiple endocrine neoplasia type 2, who carry germ line mutations in RET. However, most MTC occur in individuals without family history. Objectives. To explore the possibility that susceptibility in these cases results from low penetrance alleles of RET, its co-receptors and ligands. Design. We carried out an association study in 135 sporadic MTC (sMTC) and 533 controls from the UK-population. Results and conclusions. We analyzed 33 polymorphisms in all 9 genes involved in the 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 SNPs in the exonic regions of the GFRα2, GFRα3, GFRα4, GDNF, NRTN or PSPN genes and risk of developing sMTC. We found a strong association between the disease and specific haplotypes of RET. We have not only confirme