Genetics and Hereditary Cancers

Genetic Testing

Genetic testing looks for changes in genetic material or genes that are related to cancer risk. The process involves analyzing or reading a gene to identify mutations associated with an increased risk for cancer. However, genetic testing will not tell a person if he or she currently has cancer or if it definitely will develop in the future.

UT Southwestern genetic counselors discuss genetic testing options with patients, and then can facilitate testing through outside commercial laboratories, if recommended. Genetic testing is often done with a blood or saliva sample. If someone has had a bone marrow transplant or has an active hematologic malignancy (leukemia or lymphoma), we sometimes perform a skin biopsy instead.

Positive Genetic Test Results

A positive result on a genetic test means that a patient might be at higher risk to develop certain cancers, depending on the gene involved. Knowledge of such risk can help health care providers offer the best cancer screening options, as well as possible risk-reducing surgeries or medications.

The mutation might also impact family members, such as children, siblings, parents, aunts, uncles, cousins, and grandparents. Typically, these gene mutations are inherited from a parent, so it is likely that others in the family are at risk and not yet know. They might need genetic testing to help them understand their cancer risks.

Negative Genetic Test Results

A person’s risk for cancer does not go down to zero percent with a negative genetic test result.

When a patient receives a negative genetic test result, it means we do not know what is causing the cancers in the family. These cancers could be caused by a gene that we cannot yet test for or due to a shared environment.

When a patient receives a negative test result, there could still be a genetic reason for cancer risk in the family as a whole, even if that patient does not carry that gene or genetic mutation. For this reason, another person in the family might be recommended for genetic testing.

We call this person the “best test” in the family – a relative with the highest chance to have a hereditary cancer risk factor. This person could be a relative who was diagnosed with a certain cancer at the youngest age or a relative who has certain factors in his or her medical history that raise the risk of having a genetic reason for a given cancer.

If that relative has a positive test result, it would then affect risk for other family members. If the genetic counselor says that someone else in the family is a good candidate for genetic testing, he or she might be able to provide a letter that explains the situation to that family member to encourage genetic testing. 

Uncertain (Variant of Uncertain Significance) Genetic Test Results

Everyone has variations in their genetic information that makes them unique. Most of the time, these variations are benign and do not cause health issues.

When a patient receives an uncertain result, it means that a change, also known as a variant of uncertain significance, was identified with testing and that we currently do not have enough data about that specific variant to determine if it is a benign change or one that could be associated with cancer.

Uncertain results are not used to make any decisions about a patient’s care. These uncertain variants sometimes get reclassified once we are able to learn more about the particular variant(s), at which point there might be an impact on that patient’s care or health management. 

Genetic counselors can help patients determine what their risks might be and what is recommended for them.

Updated Genetic Testing, or Panel Testing

In 2013, newer technology became available to simultaneously test many genes at a time with one blood sample. Some people call this “panel” testing because it allows us to look at a panel of genes, but it’s also known as “next-generation sequencing.”

Panel testing can reduce costs and time to get all results because we do not have to order separate tests for every gene we want to analyze. It also gives us the opportunity to test for a number of rare genes that health insurance would seldom cover in the past.

For example, in hereditary breast cancer, the BRCA1 and BRCA2 genes are the most common genes involved. However, we now know that at least 15 other genes can impact breast cancer risk in rare families. We can examine these genes in one test through the newer testing technology. The panel testing can include the BRCA1 and BRCA2 genes to ensure that these results are up to date if a person has had some of those genes tested previously.

It’s important to remember that panel testing is not like other blood tests. As with any genetic testing, this type of testing has risks and limitations, such as unexpected or uninformative results (such as variants of uncertain significance), difficulty with result interpretation, potential issues with insurance coverage, and other strictures. We recommend a detailed conversation with a genetic counselor about this technology and the issues surrounding it.