Thyroid cancer originates in the butterfly-shaped gland at the base of the neck and is the most common malignancy of the endocrine system. The thyroid gland produces hormones that regulate metabolism and heart rate. Cancer develops when cells within the gland mutate and grow uncontrollably. While the disease is not always directly inherited, changes in a person’s DNA play a definite role in its development.
Understanding Hereditary and Sporadic Thyroid Cancer
Thyroid cancer cases fall into two groups based on how genetic changes occur: sporadic and hereditary. The vast majority of diagnoses (approximately 90% to 95%) are sporadic, meaning they do not run in families. In sporadic cases, the genetic mutation is acquired during a person’s lifetime and is confined only to the tumor cells, known as a somatic mutation.
Hereditary, or familial, thyroid cancer accounts for the remaining 5% to 10% of cases and involves a mutation passed down from a parent. These inherited changes are called germline mutations because they are present in all body cells, significantly increasing the lifetime risk of developing the disease. Hereditary cases often develop at an earlier age and can be more aggressive.
Specific Genetic Syndromes Linked to Thyroid Cancer
The most clearly defined hereditary form is Medullary Thyroid Cancer (MTC), which accounts for less than 5% of all thyroid malignancies. About 25% of MTC cases are hereditary, primarily as a component of Multiple Endocrine Neoplasia type 2 (MEN 2) syndromes. MEN 2 syndromes are inherited in an autosomal dominant pattern and are caused by a mutation in the RET proto-oncogene, located on chromosome 10.
The RET gene provides instructions for a protein that acts as a receptor on the cell surface. Its mutation leads to constant activation, causing uncontrolled cell growth. MEN 2 is categorized into three subtypes: MEN 2A, MEN 2B, and Familial Medullary Thyroid Carcinoma (FMTC). While all three involve a high risk of MTC, MEN 2A and MEN 2B also include other endocrine tumors, such as pheochromocytomas and parathyroid tumors.
Other less common inherited conditions can increase the risk for non-medullary thyroid cancers, such as papillary and follicular carcinomas. These syndromes include Familial Adenomatous Polyposis (FAP), linked to the APC gene, and Cowden Syndrome, associated with the PTEN gene. These genes normally suppress tumor growth, and their mutation can predispose an individual to thyroid and other cancers.
Non-Genetic Factors Contributing to Risk
While genetics can predispose an individual to thyroid cancer, non-inherited factors also play a significant role in increasing risk. The most established environmental risk factor is exposure to ionizing radiation, especially during childhood. This exposure can come from prior medical treatments to the head and neck, or from radioactive fallout following nuclear accidents. The risk is highest when exposure occurs at a young age, with cancer potentially developing five or more years later.
Demographic factors also influence risk, as thyroid cancer occurs nearly three times more often in women than in men. Age is also a factor, with risk generally increasing as a person gets older, though the peak incidence occurs at an earlier age for women than for men. Geographic location and diet can contribute to risk, particularly concerning iodine intake. Both chronically low and excessively high levels of dietary iodine influence the risk of developing certain types of thyroid cancer.
What Family History Means for Screening and Testing
A family history of thyroid cancer, particularly in a first-degree relative (parent or sibling), is an important consideration, even without a known genetic syndrome. For individuals with a family member who has Medullary Thyroid Cancer, genetic testing for the RET gene mutation is generally recommended. If this specific germline mutation is found, prophylactic thyroid removal may be performed, often in childhood, to prevent cancer development.
For the majority of people, routine screening for thyroid cancer (such as neck exams or ultrasounds) is not generally recommended in the absence of symptoms. However, a more proactive approach is warranted for individuals with a known hereditary syndrome or a strong family history of non-medullary thyroid cancer. This might involve regular surveillance, such as neck ultrasound monitoring, determined in consultation with a physician or genetic counselor. Genetic counseling is a crucial step for at-risk individuals and their families to understand their specific risk profile and make informed decisions about testing and monitoring.