Genetic Testing for Hereditary Cancer Syndromes (Fact Sheet)

What genetic tests are available for cancer risk?

More than 50 hereditary cancer syndromes have been described. The majority of these are caused by highly penetrant mutations that are inherited in a dominant fashion. The list below includes some of the more common inherited cancer syndromes for which genetic testing is available, the gene(s) that are mutated in each syndrome, and the cancer types most often associated with these syndromes. 

Hereditary breast cancer and ovarian cancer syndrome

• Genes: BRCA1, BRCA2
• Related cancer types: Female breast, ovarian, and other cancers, including prostate, pancreatic, and male breast cancer

Li-Fraumeni syndrome

• Gene: TP53
• Related cancer types: Breast cancer, soft tissue sarcoma, osteosarcoma (bone cancer), leukemia, brain tumors, adrenocortical carcinoma (cancer of the adrenal glands), and other cancers

Cowden syndrome (PTEN hamartoma tumor syndrome)

• Gene: PTEN
• Related cancer types: Breast, thyroid, endometrial (uterine lining), and other cancers

Lynch syndrome (hereditary nonpolyposis colorectal cancer)

• Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
• Related cancer types: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract, stomach, brain, and breast cancers

Familial adenomatous polyposis

• Gene: APC
• Related cancer types: Colorectal cancer, multiple non-malignant colon polyps, and both non-cancerous (benign) and cancerous tumors in the small intestine, brain, stomach, bone, skin, and other tissues

Retinoblastoma

• Gene: RB1
• Related cancer types: Eye cancer (cancer of the retina), pinealoma (cancer of the pineal gland), osteosarcoma, melanoma, and soft tissue sarcoma

Multiple endocrine neoplasia type 1 (Wermer syndrome)

• Gene: MEN1
• Related cancer types: Pancreatic endocrine tumors and (usually benign) parathyroid andpituitary gland tumors

Multiple endocrine neoplasia type 2

• Gene: RET
• Related cancer types: Medullary thyroid cancer and pheochromocytoma (benign adrenal gland tumor)

Von Hippel-Lindau syndrome

• Gene: VHL
• Related cancer types: Kidney cancer and multiple noncancerous tumors, including pheochromocytoma

Who should consider genetic testing for cancer risk?

Many experts recommend that genetic testing for cancer risk should be strongly considered when all three of the following criteria are met:

• The person being tested has a personal or family history that suggests an inherited cancer risk condition
• The test results can be adequately interpreted (that is, they can clearly tell whether a specific genetic change is present or absent)
• The results provide information that will help guide a person’s future medical care

The features of a person’s personal or family medical history that, particularly in combination, may suggest a hereditary cancer syndrome include:

• Cancer that was diagnosed at an unusually young age
• Several different types of cancer that have occurred independently in the same person
• Cancer that has developed in both organs in a set of paired organs, such as both kidneys or both breasts
• Several close blood relatives that have the same type of cancer (for example, a mother, daughter, and sisters with breast cancer)
• Unusual cases of a specific cancer type (for example, breast cancer in a man)
• The presence of birth defects, such as certain noncancerous (benign) skin growths or skeletal abnormalities, that are known to be associated with inherited cancer syndromes
• Being a member of a racial/ethnic group that is known to have an increased chance of having a certain hereditary cancer syndrome and having one or more of the above features as well

It is strongly recommended that a person who is considering genetic testing speak with a professional trained in genetics before deciding whether to be tested. These professionals can include doctors, genetic counselors, and other health care providers (such as nurses, psychologists, or social workers). Genetic counseling can help people consider the risks, benefits, and limitations of genetic testing in their particular situation. Sometimes the genetic professional finds that testing is not needed.

Genetic counseling includes a detailed review of the individual’s personal and family medical history related to possible cancer risk. Counseling also includes discussions about such issues as:

• Whether genetic testing is appropriate, which specific test(s) might be used, and the technical accuracy of the test(s)
• The medical implications of a positive or a negative test result (see below)
• The possibility that a test result might not be informative—that is, that the information may not be useful in making health care decisions (see below)
• The psychological risks and benefits of learning one’s genetic test results
• The risk of passing a genetic mutation (if one is present in a parent) to children

Learning about these issues is a key part of the informed consent process. Written informed consent is strongly recommended before a genetic test is ordered. People give their consent by signing a form saying that they have been told about, and understand, the purpose of the test, its medical implications, the risks and benefits of the test, possible alternatives to the test, and their privacy rights.