Familial nonmedullary thyroid cancer: a review of the genetics.
OBJECTIVE
Thyroid cancer, the commonest of endocrine malignancies, continues to increase in incidence with over 19,000 new cases diagnosed in the European Union per year. Although nonmedullary thyroid cancer (NMTC) is mostly sporadic, evidence for a familial form, which is not associated with other Mendelian cancer syndromes (e.g., familial adenomatous polyposis and Cowden's syndrome), is well documented and thought to cause more aggressive disease. Just over a decade ago, the search for a genetic susceptibility locus for familial NMTC (FNMTC) began. This review details the genetic studies conducted thus far in the search for potential genes for FNMTC.


METHODS
An electronic PubMed search was performed from the English literature for genetics of FNMTC and genetics of familial papillary thyroid carcinoma (subdivision of FNMTC). The references from the selected papers were reviewed to identify further studies not found in the original search criteria.


RESULTS
Six potential regions for harboring an FNMTC gene have been identified: MNG1 (14q32), TCO (19p13.2), fPTC/PRN (1q21), NMTC1 (2q21), FTEN (8p23.1-p22), and the telomere-telomerase complex. Important genes reported to have been excluded are RET, TRK, MET, APC, PTEN, and TSHR.


CONCLUSIONS
The genetics of FNMTC is an exciting field in medical research that has the potential to permit individualized management of thyroid cancer. Studies thus far have been on small family groups using varying criteria for the diagnosis of FNMTC. Results have been contradictory and further large-scale genetic studies utilizing emerging molecular screening tests are warranted to elucidate the underlying genetic basis of FNMTC.
Khan
Ayesha
A
Department of Endocrine Surgery, Chelsea and Westminster NHS Trust, London, United Kingdom. ayesha.khan@doctors.org.uk
Smellie
James
J
Nutting
Chris
C
Harrington
Kevin
K
Newbold
Kate
K
D002291:Carcinoma, Papillary / Q000235:genetics / Q000628:therapy; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D020412:Multifactorial Inheritance; D057285:Precision Medicine; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy