Identifying Your Genetic Risk of Cancer

February 19, 2019

Patients should consider genetic testing when cancer runs in the family.

MANY CANCERS BEGIN as a fluke mutation in a single cell. Yet in up to 10 percent of cancer cases, one or more mutations wind their way through family trees with a chance of affecting each new member. When mutations are deemed hereditary, they are present in every cell, including egg and sperm, and can thus be passed on to subsequent generations.

Each person has 46 chromosomes — 23 from each parent — that contain 20,000 to 25,000 genes. These chromosome pairs allow for a backup, so a mutated gene’s healthy counterpart can code for the correct protein. For a hereditary cancer to develop, both copies of the gene must be affected, although it is also possible to develop such a cancer if one mutated gene is inherited and its backup develops a mutation later in life.

Inheriting a mutation doesn’t mean it’s certain that someone will develop cancer — but it does put that person at risk. Researchers have identified many inherited mutations that account for more than 50 hereditary cancer syndromes.

For instance, the lifetime risk of developing breast cancer or ovarian cancer is significantly increased for a woman if she inherits a BRCA mutation. In addition to breast cancer and ovarian cancer in women, BRCA mutations are associated — to a lesser degree — with an increased risk of fallopian tube cancer and peritoneal cancer in women, breast cancer and prostate cancer in men, and pancreatic cancer in both men and women.

For patients with breast cancer and ovarian cancer, early identification of a BRCA mutation will significantly help in creating a treatment plan. Patients who test positive for a BRCA mutation may respond to certain therapies better than those who do not have the mutation, and may be eligible for different clinical trials.

Inherited gene mutations can’t be repaired, but they can be found through genetic testing. Requiring little more than a simple blood draw or saliva sample, genetic testing is now available for dozens of hereditary cancer syndromes, which are caused by alterations in genes that suppress or activate tumor growth. But genetic testing should only be done within the framework of genetic counseling.

Genetic counselors help patients decide whether to undergo genetic testing and help them understand the results and provide context. Working with genetics professionals, patients and their families can explore the possible consequences of genetic testing and develop realistic expectations of what might or might not be learned in the process.

Patients might be candidates for genetic testing if they have one or more of the following:

  • Early-onset cancer (usually before age 50)
  • More than one cancer diagnosis
  • A strong family history of cancer or the presence of rare cancers

The details of what constitutes “early-onset” or “strong family history” vary according to the cancer type or specific genetic mutation. A pedigree is created based on family history of cancer to determine who will most likely benefit from genetic testing.

Genetic counselors work with patients to develop a pedigree of family relationships that uses lines and symbols to create a visual diagram of links among family members who have a genetic disease, such as cancer.

Testing can provide information that either confirms high-risk status or rules out the presence of a genetic alteration found in other family members. For those who test positive for certain genetic mutations, increased screening might be needed. Some patients might also consider chemoprevention strategies to help lower their risk of second cancers or recurrence. In other cases, cancer could be prevented with certain prophylactic procedures and behaviors.

Because gene alterations often predispose individuals to many types of cancer, identifying genetic status early can aid diagnosis and medical decision making.

Not everyone suspected of having a genetic mutation should necessarily be tested, for example, if the results wouldn’t alter the patient’s medical course.

Patients considering genetic counseling should visit cancer.gov/cancertopics/genetics/directory to find a local genetic counselor.

Taking Charge of Your Own Genetic Testing? Take Some Precautions, Too.

People who suspect that they are predisposed to a certain inherited cancer, and who want to be tested to find out if they specific gene mutations, have a growing variety of genetic tests from which to choose.

Testing is offered for many of the more common inherited syndromes that can cause cancer, including: hereditary breast cancer and ovarian cancer syndrome, caused by mutations in the BRCA1 or BRCA2 genes; Li-Fraumeni syndrome; Cowden syndrome; Lynch syndrome; familial adenomatous polyposis; retinoblastoma; multiple endocrine neoplasia type 1 (Wermer syndrome); multiple endocrine neoplasia type 2; and Von Hippel-Lindau syndrome.

The tests for these mutations are often prescribed by a physician and require a small sample of body fluid or tissue — blood, saliva, cells from inside the cheek, skin cells or amniotic fluid. The tests are then sent to a lab and later returned to a doctor or genetic counselor, who can explain the results to patients.

However, there are tests out there that can be taken without a doctor’s prescription or guidance. These are called direct-to-consumer (DTC) genetic tests that are often marketed to people online. They can be purchased via the Internet and may require a cheek swab or saliva sample that people can send through the mail. Test results are then sent back via mail, online or over the phone.

While people are hoping to find answers about their genetic risks, they may not fully comprehend the results. This is a problem that the U.S. Food and Drug Administration and Centers for Disease Control and Prevention have pointed out with DTC genetic tests. Both agencies have stated that some of these tests lack scientific validity and should be taken into context only after a full medical evaluation.

The National Cancer Institute (NCI) advises seeing a genetic counselor, doctor or other health care professional trained in genetics to discuss results and what the next steps should be. These may include preventive care, screening, referral to support groups, the provision of emotional support and help with decisions about whether other family members need to be tested.

For those who do choose to go with a DTC genetic test, the NCI suggests using a laboratory that meets both state and federal testing guidelines. Currently, labs that perform genetic testing are subject to the federal Clinical Laboratory Improvement Amendments.

While their ease of access may make these tests appealing, they do not come without a price. The cheaper tests run around a couple of hundred dollars, and panels testing for multiple conditions or gene mutations can cost into the thousands. It’s important to note that, often, these costs are not covered by health insurance.

What’s Driving Your Cancer?

When cancer is diagnosed — whether the condition is inherited or not — it’s more important than ever that patients and their doctors consider whether the disease is driven by any faulty genes or proteins that are treatable with targeted drugs.

If tests show that this is the case, patients may be able to take drugs that specifically target these glitches, rather than chemotherapies that affect their whole bodies. For some patients, these targeted drugs can be more effective and cause fewer side effects than chemotherapy.

The FDA has approved targeted drugs for the treatment of a variety of cancers, including lung, which can be driven by EGFR mutations or ALK rearrangements; melanoma, which can arise from BRAF mutations; breast, which can overexpress the protein HER2; and colorectal, which can feed off the overexpressed proteins EGFR or VEFG. Other cancers for which targeted therapies have been approved include stomach, bladder, cervical, head and neck, kidney, liver, pancreatic, prostate, gastrointestinal stromal tumor and some blood diseases.

Scientists are finding that cancers that originate in different parts of the body may share the same mutations. That means that, even if there is no targeted treatment approved for a particular cancer, there may be one on the market, or in clinical trials, that could work for a patient. Furthermore, new mutations may emerge as a cancer progresses, or in response to treatment. Therefore, it’s important that patients diagnosed with cancer or a recurrence ask their doctors to test them for any mutations that are known to be targetable with drugs.


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