Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.
Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.
Basal cell carcinoma (BCC) is the most common malignancy in people of European descent, with an associated lifetime risk of 30%. While exposure to ultraviolet radiation (UV) is the risk factor most closely linked to the development of BCC, other environmental factors (such as ionizing radiation, chronic arsenic ingestion, and immunosuppression) and genetic factors (such as family history, skin type, and genetic syndromes) also potentially contribute to carcinogenesis. In...
Thyroid cancer represents approximately 3% of malignancies occurring in the United States, accounting for an estimated 48,020 cancer diagnoses and 1,740 cancer deaths per year. Of these cancers, 2% to 3% are medullary thyroid cancer (MTC).[2,3]
MTC arises from the parafollicular calcitonin-secreting cells of the thyroid gland. MTC occurs in sporadic and familial forms and may be preceded by C-cell hyperplasia (CCH), though CCH is a relatively common abnormality in middle aged adults.[4,5]
Average survival for MTC is lower than that for more common thyroid cancers, e.g., 83% 5-year survival for MTC compared with 90% to 94% 5-year survival for papillary and follicular thyroid cancer.[3,6] Survival is correlated with stage at diagnosis, and decreased survival in MTC can be accounted for in part by a high proportion of late-stage diagnosis.[3,6,7]
In addition to early stage at diagnosis, other factors associated with improved survival in MTC include smaller tumor size, younger age at diagnosis, familial versus sporadic form, and diagnosis by biochemical screening (i.e., screening for calcitonin elevation) versus symptoms.[7,8,9,10]
A Surveillance, Epidemiology, and End Results (SEER) population-based study of 1,252 MTC patients found that survival varied by extent of local disease. For example, the 10-year survival rates ranged from 95.6% for disease confined to the thyroid gland to 40% for those with distant metastases.
Hereditary Medullary Thyroid Cancer
While the majority of MTC cases are sporadic, approximately 20% to 25% are hereditary because of mutations in the RET (REarranged during Transfection) proto-oncogene.[11,12,13] Mutations in the RET gene cause Multiple Endocrine Neoplasia type 2 (MEN 2), an autosomal dominant disorder associated with a high lifetime risk of MTC. Multiple endocrine neoplasia type 1 (MEN 1) (OMIM) is an autosomal dominant endocrinopathy that is genetically and clinically distinct from multiple endocrine neoplasia type 2 (MEN 2); however, the similar nomenclature for MEN 1 and MEN 2 may cause confusion. Of note, there is no increased risk for thyroid cancer for MEN 1.
Historically, MEN 2 has been classified into three subtypes based on the presence of other clinical manifestations: