Genetic testing

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science

This page was updated on July 12, 2022.

Cancer is caused by the uncontrolled growth of abnormal cells, a process triggered by mutations in the cells’ genes. As these cells multiply, they cluster together to form tumors or crowd out healthy cells in the bloodstream. Most cancers occur by chance or sporadically. Gene changes may result from a random mistake when cells divide. Genes may also change in response to lifestyle habits and/or environmental exposures or injuries.

People in some families have what is known as a hereditary cancer syndrome, a cancer risk that runs in the family. These syndromes are classified by a specific gene mutation or mutations that are passed down from one generation to the next. Certain syndromes may be linked to the risk of developing multiple cancers. For instance, patients with Lynch syndrome, linked to the mutation of several genes, are at high risk of developing several reproductive or gastrointestinal cancers. Hereditary cancer syndromes are associated with 10 percent of all cancer diagnoses. However, not everyone who is born with a tendency for a gene mutation will develop cancer.

Hereditary risk assessment

During your initial evaluation period at City of Hope, you will fill out a questionnaire that includes questions about your personal and family history of cancer. This information will help determine whether you are a candidate for genetic testing.

The following are some indications of a hereditary cancer risk:

Genetic testing may be useful in helping you make informed decisions about how to manage future risks of cancer. For example, if it is determined that you are at greater risk than the “average” patient for breast cancer recurrence, we may recommend adding breast MRIs to your routine screenings. Also, if you are a woman who has breast cancer and you find out that you have an inherited risk, you may be at an increased risk for developing ovarian cancer. We will present you with options that may reduce that risk. If you already have cancer, testing may help determine whether it resulted from an inherited gene mutation or whether you are at an increased risk of developing a second cancer.

A genetic test requires a DNA sample that can be obtained from blood, saliva or a mouthwash sample. Before and after your test, you may choose to meet with a genetic counselor to discuss your questions and concerns. You will learn about the role of genes and hereditary in the development of cancer and which of your family members may be affected. The test results may also help your doctor develop a care plan individualized just for you.

Understanding genetic testing results

You may undergo a genetic test to determine whether your DNA includes one or more inherited changes—called variants or mutations—associated with cancer. Experts think inherited variants cause 5 to 10 percent of all cancers, according to the National Cancer Institute (NCI).

The genetic test may be for a specific variant or a panel screening of your genes for a wide group of changes.

Possible genetic test results include:

  • Positive
  • Negative
  • Uncertain significance

What does a positive result mean?

If your test comes back positive, that means you have a variant known to be associated with increased risks for cancer.

  • If you’ve already been diagnosed with cancer, the test may confirm that it was likely caused by this variant and provide information about risks for other cancers to occur.
  • If you don’t have cancer, the test indicates you have a higher-than-normal chance of developing the types of cancer associated with the variant.

To lower your risk, your doctor may recommend increased and earlier cancer screenings, options to reduce cancer risks and lifestyle changes.  

More specifically, a positive genetic test result associated with a high risk may lead you to consider surgical removal of certain organs and tissues impacted by the variant. Some women at high risk of ovarian cancer, for example, have opted to have their ovaries removed.

Most notably, some women have chosen to have their breasts removed after learning they have inherited a mutation in one of these genes:

  • BRCA1
  • BRCA2
  • PALB2
  • PTEN
  • TP53

Removal doesn’t eliminate all breast tissue, so some risk remains that cancer may develop. Surgery also affects how the body looks and feels, and often impacts a patient's self-image and relationship with her partner. Younger women have more risk reduction from removal, simply because they potentially have more years of life ahead of them. According to the NCI, bilateral prophylactic mastectomies may reduce cancer risk by 95 percent or more if you carry a BRCA1 or BRCA2 gene mutations, and by as much as 90 percent if you have a strong family history of breast cancer.

The NCI also estimates that removal of ovaries and fallopian tubes may reduce the chances of developing ovarian cancer by about 90 percent and breast cancer by 50 percent, if you’re at high risk for these diseases.

Most genetic variants are inherited from a parent, meaning siblings and other relatives may also have increased cancer risks, and that risk may be passed to your children.

It’s important to remember that a positive result doesn’t mean someone will develop cancer but that the cancer risks are higher than average. Your oncologist or genetic counselor may help you better understand your situation.

What about a negative result?

There are several possible reasons for a negative test result:

  • If testing for a specific variant or mutation that has already been found in a relative, a negative test result shows you don’t have that variant. In that case, you wouldn’t share the same cancer risk with other family members who have tested positive for the variant. This result is called a “true negative.” It doesn’t mean you have no risk of developing cancer; you just don’t have the increased risk of someone with that variant.
  • If your family has a notable history of cancer, but genetic testing hasn’t found a variant or mutation in the family, this is called an “uninformative negative.” In such cases, recommendations for medical management and cancer screening should be based on the family history or any personal history of cancer. Uninformative negative results may happen when:
    • Cancer in the family was caused by lifestyle choices (smoking, for example), diet or environmental exposures that relatives have in common.
    • There's a mutation that can't be detected, either in a known or undiscovered cancer risk gene..

What is a variant of uncertain significance (VUS)?

When genetic testing finds a variant of unknown or uncertain significance, it means health experts don’t yet know whether that genetic change is harmless or benign, or if it heightens your risk of developing cancer. Most of these variants eventually are classified as benign, but some are later discovered to be linked to inherited and increased cancer risks. For these reasons, if genetic test results find a variant of uncertain significance, you should check in periodically with your doctor or genetic counselor to see whether research eventually reveals whether the variant is innocuous or increased cancer risks.

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