Gene

Biology

Colorectal cancer

Familial adenomatous polyposis

Mutation

Thyroid cancer

Germline

Cancer syndrome

Genetics

Bioinformatics

Germline mutation

Papillary thyroid cancer

Internal medicine

Cowden syndrome

Multiple endocrine neoplasia

Oncology

Medicine

Disease

Cancer

Medullary thyroid cancer

Thyroid

Genes

The thyroid is the most common site of endocrine cancer. One type of thyroid cancer, non-medullary thyroid cancer (NMTC), develops from follicular cells and represents approximately 90% of all thyroid cancers. Approximately 5%-15% of NMTC cases are thought to be of familial origin (FNMTC), which is defined as the occurrence of the disease in three or more first-degree relatives of the patient. It is often divided into two groups: Syndrome-associated and non-syndromic. The associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex and Werner syndrome. The hereditary factors contributing to the unfavorable course of FNMTC remain poorly understood; therefore, considerable effort is being expended to identify contributing loci. Research carried out to date identifies fourteen genes (DICER1, FOXE1, PTCSC2, MYH9, SRGAP1, HABP2, BRCA1, CHEK2, ATM, RASAL1, SRRM2, XRCC1, TITF-1/NKX2.1, PTCSC3) associated with vulnerability to FNMTC that are not related to hereditary syndromes. In this review, we summarize FNMTC studies to date, and provide information on genes involved in the development of non-syndromic familial non-medullary thyroid cancers, and the significance of mutations in these genes as risk factors. Moreover, we discuss whether the genetic polymorphism rs966423 in DIRC3 has any potential as a prognostic factor of papillary thyroid cancer.

Current Knowledge of Germline Genetic Risk Factors for the Development of Non-Medullary Thyroid Cancer