Hereditary Cancer Syndromes List

In many cases, cancer is a mystery. There is still much to be learned about what causes it. However, through extensive research, scientists have identified several gene mutations that increase the risk of cancer and can be passed from parent to child. Collectively, these gene mutations are known as hereditary cancer syndromes.

Tampa General Hospital offers individualized genetic counseling services through our highly acclaimed Cancer Genetics Program. We provide valuable information and support to people who have—or may be at risk of having—a family cancer syndrome.

What Causes Hereditary Cancer Syndromes?

In general, cancer arises when healthy cells undergo abnormal DNA changes that cause them to grow uncontrollably. The excess cells then build up, bind together and form tumors.

Each cell in the body has strands of DNA (genes) that instruct the cell on how to produce the proteins it needs for proper function. Each protein has a specific job. For instance, some proteins help the cell replicate by growing and dividing, while other proteins keep cell growth under control.

Every person receives one complete copy of their genes from their mother and another complete copy from their father. Over many years, multiple gene mutations can accumulate, disrupting the normally orderly process of cell growth and allowing a healthy cell to grow uncontrollably and eventually transform into a cancerous cell.

To date, scientists have identified more than 50 family cancer syndromes, and experts believe that up to 10% of cancers are hereditary. However, the vast majority of cancer cases occur without a significant family history and are not inherited.

What Are the Signs of a Hereditary Cancer Syndrome?

It is important to understand that cancer can sometimes seem to “run in families” even though it is not caused by a hereditary cancer syndrome. For instance, a shared lifestyle choice, such as tobacco use, can cause similar cancers to develop among family members without an inherited gene mutation.

With that said, certain factors increase the likelihood that the cancers in a family are caused by a hereditary cancer syndrome. Those factors include:

  • Multiple cases of the same type of cancer, especially if it is uncommon
  • Cancers that develop at a younger age than usual
  • More than one type of cancer in one family member, such as a woman who is diagnosed with breast and ovarian cancer
  • Cancers that affect both organs in a pair, such as the breasts or kidneys
  • Childhood cancers in siblings, such as sarcomas in a brother and sister
  • Cancer in the gender less frequently affected, such as breast cancer in a man
  • Cancer in several generations, such as a grandfather, father and son

In general, cancer in a close relative, such as a parent or sibling, is more of a red flag than cancer in a more distant relative.

How Are Hereditary Cancer Syndromes Diagnosed?

Through genetic testing, a physician can determine whether a patient carries a gene mutation that predisposes them to cancer. In addition to confirming whether the patient’s cancer is a result of a hereditary cancer syndrome, genetic testing can determine whether the patient’s family members who have not developed the cancer have inherited the same harmful gene mutation.

Even if a hereditary cancer syndrome is diagnosed, not all family members who inherit the harmful gene mutation will necessarily develop cancer. Many factors can influence the development of cancer, including environmental exposures and lifestyle choices. Additionally, family cancer syndromes can vary in terms of expressivity, which is the complex process through which the instructions encoded in a gene are carried out and affect cellular function.

Hereditary Cancer Syndromes Treatment

The treatment of hereditary cancer syndromes can vary depending on the type and stage of the cancer and other unique factors. Some strategies include:

  • Surveillance – To help detect any cancer early, a physician will typically recommend a screening plan, which may include frequent physical exams, blood work, imaging studies and/or genetic testing.
  • Risk reduction – Some patients elect preventive surgery to remove tissues and organs affected by the hereditary cancer syndrome, such as a prophylactic mastectomy (removal of the breasts) or prophylactic oophorectomy (removal of the ovaries).
  • Chemoprevention – Certain medications, such as selective estrogen receptor modulators (SERMs) and aromatase inhibitors, may be prescribed to reduce the risk of breast cancer in individuals with specific gene mutations.
  • Targeted therapies – If cancer is diagnosed, certain drugs may be prescribed to target the precise genetic characteristics of the tumor and inhibit specific genetic mutations or signaling pathways.
  • Traditional cancer treatments – If cancer is diagnosed, traditional treatments such as surgery, chemotherapy and radiation therapy may be used to remove or destroy the cancerous cells.

Researchers have identified dozens of gene mutations in certain cancers that indicate whether the tumor will be susceptible or resistant to different anti-cancer therapies. As the number of known variants in mutated genes continues to increase, genetic testing is becoming a more powerful tool for treating cancer.

Types of Hereditary Cancer Syndromes

Examples of family cancer syndromes include:

Hereditary Breast and Ovarian Cancer Syndrome

Caused by a harmful mutation in breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2), hereditary breast and ovarian cancer syndrome (HBOC) is a genetic condition that significantly increases the lifetime risk of breast and ovarian cancer. HBOC also increases the risk of fallopian tube, prostate, pancreatic, peritoneum, male breast and melanoma skin cancer.

BRCA1 and BRCA2 are tumor suppressor genes (anti-oncogenes). When functioning properly, anti-oncogenes produce proteins that regulate cell growth and suppress tumor formation. A harmful gene mutation can interfere with this vital process, resulting in uncontrolled cell growth that leads to the development of cancer.

Cowden Syndrome

Associated with mutations in the PTEN gene, Cowden syndrome (CS) increases the risk of certain cancers, including breast, thyroid, uterine, kidney, colorectal and melanoma skin cancer. CS can also cause benign, tumor-like growths (hamartomas) on the skin and mucous membranes as well as in the intestinal tract and brain.

PTEN is a tumor suppressor gene that normally prevents cells from growing and dividing uncontrollably. A harmful mutation in the PTEN gene can lead to unrestrained cell division and the formation of hamartomas and cancerous tumors.

Lynch Syndrome

As cells grow and replicate over their lifecycle, they make copies of their DNA. Sometimes, the copies have errors. The body has a set of genes known as DNA mismatch repair genes, which have instructions for finding these errors and fixing them. Lynch syndrome is caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2.

Also known as hereditary non-polyposis colorectal cancer syndrome (HNPCC), Lynch syndrome increases the risk of early-onset colorectal cancer (before age 50), uterine cancer and other extracolonic tumors. A variant known as Muir Torre Syndrome is associated with an increased risk of certain skin tumors.

Hereditary Leukemia and Hematologic Malignancies Syndromes

Hematologic malignancies are cancers that affect the lymph nodes, bone marrow and blood. There are several types, including leukemia, myelodysplastic syndrome (MDS), lymphoma and multiple myeloma. In some cases, the cancer is related to a harmful inherited gene mutation. Scientists have linked hematologic malignancies to mutations in the:

  • RUNX1 gene – Increases the risk of MDS, acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia
  • CEBPA gene – Increases the risk of AML
  • GATA2 gene – Increases the risk of MDS and AML

While large-scale studies have not yet been completed, experts estimate that approximately 10% of hematologic malignancies have an inherited component.

Familial Adenomatous Polyposis

Associated with harmful mutations in a tumor suppressor gene known as the APC gene, familial adenomatous polyposis (FAP) is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colon polyps (adenomas) form in the gastrointestinal tract. Although the adenomas mainly develop in the colon and rectum, they can also occur in the small intestine and stomach.

Attenuated FAP (AFAP) is a milder form of FAP that also increases the risk of colon cancer but causes fewer colon polyps.

Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a rare inherited familial predisposition to several types of cancer. In addition to soft tissue sarcomas in fat, muscles, nerves, joints, blood vessels, bones and deep layers of skin, LFS is associated with:

  • Breast cancer
  • Leukemia
  • Lung cancer
  • Brain tumors
  • Adrenal gland cancer

Studies show that women with LFS have a nearly 100% chance of developing breast cancer. Additionally, anyone with LFS has a 90% chance of developing one or more types of cancer during their lifetime, as well as a 50% chance of developing cancer before age 30.

Most people with LFS are found to have a harmful mutation in a tumor suppressor gene known as TP53.

Von Hippel-Lindau Disease

Von Hippel-Lindau disease (VHL) is a rare, multi-system disorder caused by a harmful mutation in the tumor suppressor gene known as the VHL gene. The condition is characterized by the abnormal growth of blood vessels (hemangioblastomas), which can develop in the retinas, certain areas of the brain, the spinal cord and other parts of the nervous system. Additionally, tumors and cysts can develop in the:

  • Adrenal gland
  • Inner ears
  • Kidneys
  • Pancreas
  • Reproductive tract

VHL also increases the risk of certain types of cancer, especially kidney cancer.

Multiple Endocrine Neoplasia

Multiple endocrine neoplasia (MEN) syndromes are inherited familial predispositions to tumor development in the endocrine glands, which secrete hormones into the bloodstream to control various bodily functions. For instance, the endocrine system is instrumental in regulating growth, development, metabolism and mood, along with sexual function and reproduction.

There are two distinct MEN syndromes:

  • MEN1 – Characterized by tumors in the pituitary gland, parathyroid gland and pancreas
  • MEN2 – Characterized by medullary thyroid cancer

Receive World-Class Care at TGH

If you have a strong family history of cancer, you may want to learn more about your genes so you and your family members can better plan your healthcare for the future. Because inherited gene mutations affect all the cells in your body, they may be detected through genetic testing performed on samples of your blood or saliva.

With that said, genetic testing is not helpful for everyone. If you would like to find out if it may be right for you, contact TGH’s Cancer Genetics Program at (800) 844-7585 to request an appointment with a genetic counselor.