What are genes?

Genes carry small individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in thyroid cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

A person may either be born with a genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Somatic mutations can sometimes be caused by environmental factors, such as cigarette smoke. Most thyroid cancers are considered sporadic, meaning that the damage to the genes occurs after a person is born, and there is no risk of passing on the gene to a person’s children. Inherited thyroid cancers are less common (about 10%) and occur when gene mutations are passed within a family, from one generation to the next.

What are the chances a mutated gene is inherited?

Every cell usually has two copies of each gene: one inherited from a person’s mother and one inherited from a person’s father. Hereditary thyroid cancer usually follows an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a gene mutation also has a 50% chance of having the same mutation.

What is a person's average risk for thyroid cancer?

A person with an average risk for thyroid cancer has less than a 1% chance of developing thyroid cancer during his or her life. Women develop thyroid cancer more often than men.

How common is thyroid cancer?

Thyroid cancer is the sixth most common cancer among women. In 2008, an estimated 37,340 adults (8,930 men and 28,410 women) in the United States will be diagnosed with thyroid cancer. It is estimated that 1,590 deaths (680 men and 910 women) from this disease will occur this year.

How can a person know if he or she has inherited a genetic mutation that increases his or her risk of thyroid cancer?

Only genetic testing can determine whether a person has a genetic mutation. Most experts strongly recommend that people considering genetic testing first consult a genetic counselor. Genetic counselors are trained to explain the risks and benefits of genetic testing.

For more information, read Genetic Testing and What to Expect When Meeting With a Genetic Counselor.

How does a person know if thyroid cancer runs in the family?

The risk of inherited thyroid cancer is low. Thyroid cancer may run in the family if first-degree relatives (parents, brothers, sisters, children) or many close relatives (first-degree relatives, grandparents, aunts, uncles, nieces, nephews, grandchildren, cousins) have been diagnosed with thyroid cancer, especially before age 30.

What is a person's risk if thyroid cancer runs in the family?

If a person's first-degree relatives developed thyroid cancer, his or her risk of thyroid cancer is greater than the average risk. The risk increases if other close relatives have thyroid cancer.

Which inherited genetic mutations raise the risk of thyroid cancer?

There are some genes associated with an increased risk of thyroid cancer. Some of the most common hereditary cancer syndromes associated with thyroid cancer risk are described below.

Medullary thyroid cancer

Medullary thyroid cancer (MTC) accounts for about 5% to 10% of all thyroid cancers. Approximately 25% of MTC are caused by an inherited cancer risk. Three conditions are responsible for hereditary MTC: multiple endocrine neoplasia (MEN) 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). These conditions are caused by mutations in the RET gene, a type of gene called a proto-oncogene. A proto-oncogene makes proteins that promote normal cell growth. Mutations in proto-oncogenes result in too much cell growth and can lead to cancer. Genetic testing for mutations in the RET gene is available.

MEN 2A. MEN 2A causes 20% to 25% of all medullary thyroid cancers. People with MEN 2A have a 95% to 100% risk of developing MTC. Families with MEN 2A also have an increased risk of developing pheochromocytoma, a tumor in the adrenal glands. The adrenal glands are located on top of each kidney and are a part of the body’s endocrine (hormonal) system. Families with MEN 2A also have an increased risk of noncancerous parathyroid tumors or an increase in the size of the parathyroid gland. The parathyroid glands are located in the neck near the thyroid gland and are part of the endocrine system. MEN 2A is diagnosed if a single person or close family members have at least two of the characteristic features. MEN 2A follows an autosomal dominant inheritance pattern, and less than 5% of people diagnosed with MEN 2A have no family history of the condition.

MEN 2B. MEN 2B causes less than 2% of all medullary thyroid cancers. People with MEN2B have an increased risk of developing MTC, pheochromocytoma, and physical abnormalities, such as a long face and long arms and legs. They also have thick, lumpy lips caused by noncancerous tumors called mucosal neuromas. Some people with MEN 2B have bowel problems. Signs of MEN 2B, including MTC, can be begin in childhood. MEN 2B is also an autosomal dominant condition, but approximately 50% of people with MEN 2B have no family history of the condition.

Familial medullary thyroid cancer (FMTC). FMTC causes less than 2% of all medullary thyroid cancers. FMTC is suspected if a person has four or more family members with MTC and no cases of pheochromocytoma or hyperparathyroidism (increase in hormone produced by the parathyroid). However, people with multiple family members with MTC should talk with their doctor about thyroid screening.

Papillary and follicular thyroid cancer

Papillary and follicular thyroid cancer make up 80% to 90% of all thyroid cancers. It is estimated that less than 5% of papillary thyroid cancer is inherited.

Familial papillary thyroid cancer. Familial papillary thyroid cancer is thought to follow an autosomal dominant inheritance pattern. However, more research is needed to identify genes associated with papillary thyroid cancer risk. For this reason, genetic testing is not currently available.

Familial adenomatous polyposis (FAP). People with FAP have a 2% risk of developing papillary thyroid cancer. The average age at thyroid cancer diagnosis is 28, and women with FAP appear to have a greater risk than men. People with FAP often develop hundreds to thousands of polyps (a growth in the colon or rectum) that are initially noncancerous, but there is almost a 100% chance that the polyps will develop into cancer if not treated. Most people with FAP develop polyps in their 20s or 30s, although polyps can be found as early as the teenage years, and colorectal cancer often develops by age 40. People with FAP also have an increased risk of other types of cancer including stomach, small bowel, pancreas, and hepatoblastoma (liver cancer that usually occurs in early childhood).

Although FAP follows an autosomal dominant inheritance pattern, approximately 30% of people with FAP have no family history of the condition. FAP is caused by a mutation on the APC gene, which is a tumor suppressor gene. A tumor suppressor gene makes proteins that prevent tumor formation by limiting cell growth. Mutations in a tumor suppressor gene cause a loss of the ability to restrict tumor growth and, as a result, cancer can develop. Genetic testing for the APC gene is available.

For more information, read the Cancer.Net Guide to Familial Adenomatous Polyposis.

Cowden syndrome (CS). People with CS have up to a 10% lifetime risk of follicular or papillary thyroid cancer; follicular thyroid cancer is most common. Approximately 70% of people with CS have noncancerous thyroid changes, including multinodular goiter (enlarged thyroid gland with multiple growths or nodules), adenomatous nodules (growth on the thyroid gland), and follicular adenomas (another type of growth on the thyroid gland). CS is a rare genetic condition caused by a mutation on the PTEN gene. People with CS also have a increased risk of both benign and cancerous tumors of the breast and endometrium (lining of the uterus). Also, people with CS often have small growths on the face or in the mouth and a larger than average head size. Genetic testing for the PTEN gene is available.

For more information, read the Cancer.Net Guide to Cowden Syndrome.

What is a person's risk level?

In addition to family history, other environmental and lifestyle factors may increase the risk of thyroid cancer. Discussing family history and personal risk factors with a doctor can help someone better understand his or her risk. People with a higher than average risk may benefit from genetic counseling and early detection strategies.

If a person is diagnosed with medullary thyroid cancer, it is recommended that testing for a germline mutation be done, because he or she might be the first person diagnosed with the tumor in a family with a mutation. Relatives, siblings, and children should then be tested for the mutation.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to thyroid cancer cannot predict that a person will develop cancer. Controllable risk factors, such as eating a balanced diet, maintaining a healthy weight, exercising, avoiding chemicals and asbestos, limiting alcoholic beverages, and avoiding tobacco products also play a role. Many people who develop thyroid cancer have few known risk factors. Research to better understand how genetic mutations cause the development of thyroid cancer and how to prevent this process is ongoing. Talk with a doctor for more information about risk factors, prevention, and screening for thyroid cancer.

Additional Resources

Cancer.Net: Genetics

Cancer.Net Guide to Thyroid Cancer