Thyroid cancer (TC) develops when cells in the butterfly-shaped gland in the neck grow out of control, forming a tumor. Most cases arise from genetic changes that occur during a person’s lifetime, often without a clear cause. However, the presence of thyroid cancer in multiple family members suggests that a predisposition can be passed down through generations. A significant minority of cases are linked to inherited genetic mutations, making the disease hereditary for some individuals.
Distinguishing Sporadic from Inherited Thyroid Cancer
The vast majority of thyroid cancer cases (approximately 90% to 95%) are classified as sporadic, meaning they do not result from an inherited genetic change. These cancers arise from somatic mutations, which are gene alterations that occur only within the thyroid cells themselves. Environmental factors, such as radiation exposure or iodine deficiency, can contribute to sporadic tumor development.
Inherited thyroid cancer is caused by a germline mutation, a genetic change present in the egg or sperm and subsequently in every cell of the offspring. This type accounts for 5% to 10% of all thyroid cancer diagnoses. The proportion of hereditary cases is much higher (about 25%) within the less common Medullary Thyroid Cancer (MTC) subtype. For the more common Non-Medullary Thyroid Cancer (NMTC), such as Papillary Thyroid Carcinoma, the familial risk is estimated to be between 5% and 15%.
Genetic Syndromes Linked to Familial Risk
The mechanism of inherited risk is tied to specific genetic syndromes. Medullary Thyroid Cancer (MTC), which develops from the thyroid’s C-cells, has the clearest hereditary link. Nearly all inherited MTC cases are caused by a germline mutation in the RET proto-oncogene. This highly penetrant mutation leads to syndromes like Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B) or Familial Medullary Thyroid Cancer (FMTC).
The RET gene provides instructions for a protein involved in cell signaling pathways that control growth and survival. When mutated, the protein becomes constantly active, driving cancer development. Because of this strong association, genetic testing for inherited RET mutations is standard for anyone diagnosed with MTC, regardless of family history.
Inherited Non-Medullary Thyroid Cancer (NMTC), typically Papillary Thyroid Carcinoma (PTC), is often more complex and less uniformly understood. This familial risk is frequently part of broader, multi-organ cancer predisposition syndromes. Examples include Cowden syndrome, caused by mutations in the tumor suppressor gene PTEN, which increases the risk of thyroid, breast, and endometrial cancers.
Familial Adenomatous Polyposis (FAP) is another associated condition, where APC gene mutations primarily cause colorectal polyps but also increase the risk for PTC. Other rare syndromes, such as Carney Complex and Werner Syndrome, have also been linked to increased susceptibility to non-medullary thyroid cancers. The inheritance pattern for many familial non-medullary cases is often autosomal dominant with reduced penetrance, meaning a person only needs one copy of the altered gene to be at risk, but not everyone who inherits it will develop the disease.
Evaluating Family History and Next Steps
Determining whether a family history warrants genetic evaluation depends on specific factors related to the type and pattern of cancer. Genetic counseling should be considered if an individual has two or more first-degree relatives (such as a parent or sibling) diagnosed with thyroid cancer. A family history of Medullary Thyroid Cancer is another strong indicator, mandating RET gene testing due to the high likelihood of an inherited syndrome.
Diagnosis of thyroid cancer at a young age (typically under 40 years old) or identification of a rare subtype, like the cribriform-morular variant of Papillary Thyroid Carcinoma, also suggests the need for genetic risk assessment. Genetic counseling involves a specialist reviewing the complete personal and family medical history to determine the potential for an inherited mutation. This consultation helps individuals understand their specific risk and decide whether genetic testing is appropriate for them and their relatives.
If a high-risk germline mutation, such as in the RET gene, is identified, surveillance shifts to intensive, risk-stratified management. For those with the highest-risk RET mutations, prophylactic removal of the thyroid gland (thyroidectomy) may be recommended, sometimes during childhood, to prevent MTC from developing. For individuals with non-medullary familial risk, surveillance protocols involve regular screening with thyroid ultrasound to detect tumors early.