House Call: Genetic Screening for Hereditary Cancer Syndromes

People with a family history of certain types of cancer may face a high risk of developing cancer themselves. Genetic counseling and testing can help these people understand their risk of hereditary cancer and their options for early detection or prevention.

Hereditary syndromes

About 5%–10% of cancers are the result of inherited genetic mutations. These mutations cause what are called hereditary cancer predisposition syndromes. Not all mutations involved in hereditary cancer predisposition syndromes have been identified, but some can be detected by blood tests. Some of the more common hereditary syndromes are listed below.

Hereditary breast and ovarian cancer syndrome is the most common cause of inherited breast cancer. This syndrome is caused by mutations in the BRCA1 and BRCA2 tumor suppressor genes. When normal, these genes help prevent uncontrolled cell growth. However, mutations in the genes can remove their protective effect and allow cancer to develop. Women who inherit a BRCA mutation are more likely to develop breast and ovarian cancers than are women who do not carry a mutation. Men with one of these mutations face an increased risk of breast and prostate cancers.

Lynch syndrome, or hereditary non-polyposis colorectal cancer syndrome, is caused by mutations in DNA mismatch repair genes. These genes normally help repair damaged cells or stop them from reproducing. But when the genes do not function properly, colorectal cancer or uterine cancer may occur at an early age.

Cowden syndrome is characterized by small, benign (noncancerous) growths called hamartomas on the skin and mucous membranes. People with Cowden syndrome also have an increased 
risk of tumors developing in the
 breast, uterus, and thyroid. Cowden syndrome is caused by a mutation of 
the PTEN gene, which controls the production of an enzyme that regulates cell growth. Mutations of this gene cause uncontrolled cell growth that results in benign or malignant (cancerous) tumors.

Other hereditary cancer predisposition syndromes include neurofibromatosis, leading to malignant nerve-sheath tumors; Gardner syndrome, leading to cancers of the gastrointestinal tract; Li-Fraumeni syndrome, leading to multiple types of cancer including breast cancer; and Von Hippel-Lindau disease, leading to cancers of the eye, brain, and spinal cord.

Genetic counseling and testing

People with two or more close relatives (parents, children, or siblings) who have had the same type of cancer may want to consider genetic testing. Likewise, some current or former cancer patients—such as those who were diagnosed at a young age, have a close relative with the same type of cancer, or have certain rare cancer types—may want to undergo genetic testing to see
if their family members are at risk.

Deciding whether to be tested for an inherited cancer-causing genetic mutation can be difficult. In addition to possibly causing a psychological burden, testing is expensive and may not be covered by insurance. Genetic counselors can help guide their clients through the decision-making process and help them decide whether genetic testing is right for them.

In a genetic counseling session, the counselor meets with the client and reviews the client’s family history of cancer to see if testing is appropriate. The counselor explains what the positive or negative results of the test mean. If the client undergoes testing, the counselor sees him or her afterward to discuss the options for follow-up cancer testing and preventive measures.

A positive result means the client has the inherited mutation that was tested for. Although not all individuals with an inherited mutation develop cancer, they do face a significantly increased risk of cancer and can take a more proactive approach to cancer screening. For example, a man with Lynch syndrome would need to have screening colonoscopies at regular intervals to detect and remove precancerous polyps. A woman who tests positive for a BRCA mutation could undergo more intensive screening, such as breast MRIs and earlier mammograms.

Preventive surgery is also an option for some people with hereditary mutations. For example, some women with BRCA mutations choose to undergo a bilateral mastectomy (removal of both breasts) to reduce their breast cancer risk by about 95% or removal of the fallopian tubes and ovaries to reduce their ovarian cancer risk by 80%–90%. Genetic counselors can help people weigh the pros and cons of these procedures.

Many hospitals and clinics that offer genetic testing also offer genetic counseling. For example, The University of Texas MD Anderson Cancer Center’s Clinical Cancer Genetics Program offers both genetic counseling and testing to current cancer patients as well as people who are not MD Anderson patients.

– B. Tutt

For more information, ask your physician, visit the Clinical Cancer Genetics Program online at www.mdanderson.org/departments/ccg, or call the Clinical Cancer Genetics Program at 844-565-2361.

OncoLog, May-June 2017, Volume 62, Issue 5-6