What is hereditary thyroid cancer?
Most cases of thyroid cancer are sporadic. This means that they occur because of a combination of hormonal, environmental, and personal risk factors. However, approximately 5-10% of thyroid cancer cases are due to cancer-causing gene changes (mutations) that are passed down from parent to child.
Families who carry these gene changes have what is known as a hereditary form of thyroid cancer. These families may benefit from identifying the precise gene change that they carry, as this may help to determine which members have a greater risk of developing cancer. This can lead to medical treatment to prevent cancer from developing, or to detect it at an earlier, more treatable stage.
What is the incidence of thyroid cancer?
The National Cancer Institute estimates that there will be more than 37,340 new cases of thyroid cancer diagnosed in the United States in 2008. Approximately 1 in 127 people develop thyroid cancer in their lifetimes, and it is about three times more common in women than in men. Most cases of thyroid cancer occur in people who are over the age of 45; rarely, it occurs in young adults and children.1
To read more about thyroid cancer risk factors, diagnosis, and treatment, go to: clevelandclinic.org/disorders/Thyroid_Cancer/hic_Thyroid_Cancer.aspx
What genes are associated with thyroid cancer?
There are likely many genes that play a role in a person's risk of developing thyroid cancer (along with the hormonal, environmental, and personal risk factors). This section focuses on the genes and hereditary cancer syndromes that are associated with a high risk of thyroid cancer.
RET: Up to 25% of cases of medullary thyroid cancer (including 5-15% of seemingly sporadic cases) are due to changes in the RET gene. An RET gene change may be associated with the following types of thyroid cancer: familial medullary thyroid carcinoma (FMTC), multiple endocrine neoplasia type 2A, or type 2B (MEN 2A or MEN 2B). People who carry an RET gene change may have a greater risk of the following: medullary thyroid cancer; endocrine complications, including hyperparathyroidism (overactivity of parathyroid glands in the neck); pheochromocytoma (adrenal gland tumor); and gastrointestinal disease.2,3
PTEN: Gene changes in the PTEN gene cause PTEN Tumor Hamartoma Syndrome, including Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Individuals with PTEN gene changes have up to a 10% chance of developing thyroid cancer. These cancers are usually the follicular type, but papillary thyroid cancer can occasionally occur in families with CS or BRRS. Individuals with CS or BRRS also have an increased chance of breast and uterine cancers and other benign tumors of the breast, thyroid, uterus, and digestive system.4,5
APC: The APC gene is associated with Familial Adenomatous Polyposis (FAP) (clevelandclinic.org/disorders/Colorectal_Cancer/hic_Hereditary_Colon_Cancer.aspx). FAP is a rare condition that is marked by the presence of hundreds to thousands of polyps in the colon. The polyps are growths, also known as adenomas, that have the potential to develop into cancer. People with FAP have an increased risk of cancers of the colon, stomach, small intestine, pancreas, thyroid, liver, and bile ducts. About 2% of individuals with FAP develop papillary thyroid cancer.6
Familial papillary carcinoma is an inherited syndrome that is associated with an increased risk of papillary thyroid cancer. Other rare syndromes also associated with hereditary thyroid cancer include Carney Complex and Werner syndrome.
What are the treatment options for people who have hereditary thyroid cancer?
If a hereditary thyroid cancer syndrome is identified, steps can be taken to reduce cancer risk, or to identify cancer at its earliest, most treatable stage. The treatment and observation depend on the genetic syndrome identified in the family. For example, people who have RET gene changes may decide to have preventive removal of the entire thyroid (a procedure known as prophylactic thyroidectomy) to prevent the development of thyroid cancer.2,3 Specific recommendations are based on the evaluation of each person, including his or her personal and family histories and genetic test results, if appropriate.
What is involved in a cancer genetic risk assessment?
Appointments for a cancer genetic risk assessment typically last one hour and include evaluation of a patient's personal medical history and family history. Based on this information, an assessment of the person's hereditary risk is created, and genetic testing is performed, when appropriate. Test results are then given to the patient and a personalized medical management plan is devised.
Who should have a cancer genetic risk assessment?
The most appropriate patients for a cancer genetic risk assessment include people who have:
- Medullary thyroid cancer
- Several relatives who are affected by thyroid or endocrine cancers
- Several types of cancer
- Clustering of cancers or tumors that are known to be genetically related (such as thyroid and other endocrine tumors or thyroid and breast, uterine, or colon cancers)
- A known cancer-causing genetic mutation in the family (e.g., a blood relative with a known RET mutation)
For more information
To schedule an appointment with a Genetic Counselor, please contact us at:
Cleveland Clinic
Genomic Medicine Institute
Center for Personalized Genetic Healthcare
9500 Euclid Avenue/NE50
Cleveland, OH 44195
216.445.5686
216.445.6935 (fax)
www.lerner.ccf.org/gmi/cpgh
References
1. National Cancer Institute: www.cancer.gov/cancertopics/types/thyroid
2. Eng C, et al. The Relationship Between Specific RET Proto-oncogene Mutations and Disease Phenotype in Multiple Endocrine Neoplasia Type 2: International RET Mutation ConsortiumAnalysis. JAMA1996;276:1575-1579.
3. Brandi ML, et al. Guidelines for Diagnosis and Therapy of MEN Type 1 and Type 2. J Clin Endocrinol Metab 2001;86:5658-5671.
4. Starink TM, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet 1986;29:222-33.
5. Eng C. PTEN: one gene, many syndromes. Hum Mutat2003;22:183-98.
6. Cetta F, et al. Germline mutations of the APC gene in patients with familial adenomatous polyposis-associated thyroid carcinoma: results from a European cooperative study. J Clin Endocrinol Metab 2000;85:286-92.
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