title: Diagnosis and Management of Hereditary Thyroid Cancer.
abstract: Thyroid cancers are largely divided into medullary (MTC) and non-medullary (NMTC) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5-15% of NMTC and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden's disease , Werner's syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20-25% of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the RET oncogene on chromosome 10q11.2. There is a clear genotype-phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery.
authors.affiliation: Department of Endocrinology and Diabetes, Thomas Addison Unit, St George's Healthcare NHS Trust, Blackshaw Road, Tooting, London, UK. gbano@sgul.ac.uk.
authors.forename: Gul
authors.initials: G
authors.lastname: Bano
authors.affiliation: St. George's, University of London, London, UK.
authors.forename: Shirley
authors.initials: S
authors.lastname: Hodgson
mesh_terms: D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D010641:Phenotype; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*
keywords: Familial; Genetic syndromes; Medullary Thyroid Cancer; Multiple Endocrine neoplasia; Oncogenes; Papillary Thyroid Cancer (non-medullary thyroid cancer); Tumour suppressor genes