title: Succinate dehydrogenase D variants do not constitute a risk factor for developing C cell hyperplasia or sporadic medullary thyroid carcinoma.
abstract: Medullary thyroid carcinoma (MTC) is a tumor that arises from parafollicular cells of the thyroid gland. MTC can occur sporadically (75%) or as part of inherited cancer syndromes (25%). In most cases, hereditary MTC evolves from preneoplastic C cell hyperplasia (CCH), so early detection of this pathology would evidently be critical. A recent study reports that alterations in succinate dehydrogenase (SDH) D are responsible for familial non-RET CCH. First, we studied SDHD in two families with hereditary non-RET CCH and found no alterations related to the inheritance of this disease. Then, we investigated whether the H50R variant could be a risk factor in the sporadic development of MTC in both Spanish and English patients. We found no evidence that the presence of the H50R is strongly associated with the risk of sporadic MTC, although we did observe an association with age at diagnosis of MTC in Spanish H50R carriers that we did not find in English patients. Finally, we looked for evidence of CCH or any other thyroid disease in a panel of germ-line SDH (B or D) mutation carriers and found none. We conclude that SDHD variants do not constitute a risk factor for developing CCH or sporadic MTC.
authors.affiliation: Hereditary Endocrine Cancer Group, Department of Human Genetics, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, E-28029 Madrid, Spain. mrobledo@cnio.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascon
authors.forename: Arancha
authors.initials: A
authors.lastname: Cebrian
authors.forename: Marina
authors.initials: M
authors.lastname: Pollan
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz-Llorente
authors.forename: Cristina
authors.initials: C
authors.lastname: Montero-Conde
authors.forename: Rocio
authors.initials: R
authors.lastname: Leton
authors.forename: Ruth
authors.initials: R
authors.lastname: Gutierrez
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Olga
authors.initials: O
authors.lastname: Gonzalez-Albarran
authors.forename: Tomas
authors.initials: T
authors.lastname: Lucas-Morante
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000209:etiology* / Q000235:genetics; D002648:Child; D006801:Humans; D006965:Hyperplasia; D008875:Middle Aged; D009154:Mutation; D011230:Precancerous Conditions / Q000209:etiology* / Q000235:genetics; D012307:Risk Factors; D013385:Succinate Dehydrogenase / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics
chemical_list: D013385:Succinate Dehydrogenase