Genetic mutations

Genetics is a pretty complicated subject, especially when it comes to cancer risk.

Genes are made up of DNA (short for deoxyribonucleic acid). Once thought termed gene mutations, gene variants—which more accurately refers to the many gene differences that arise from mutations and other phenomena—are changes to that DNA.

People may get these variants from their parents or from exposure to something in the environment that damages the DNA.

When a cell divides, it must copy all of its DNA, and mistakes may happen during this process. The result of this error is a genetic mutation or variant.

Most of the time, the body detects the error and repairs or destroys it. If not, the genetic variants may prompt cells to continue dividing and potentially lead to cancer. It’s important to remember that most gene variants don’t cause disease, and those that do are uncommon.

What are hereditary mutations?

Hereditary mutations are passed down from parents. These are present throughout life in virtually every cell in the body. They’re also called germline variants, because they’re present in the mother’s egg or father’s sperm cells (germ cells). Such inherited genetic mutations may be contributing cause to about 5 percent to 10 percent of all cancers, according to the National Cancer Institute.

These handed-down variants may be factors in 50 known hereditary cancer syndromes, including:

• Li-Fraumeni syndrome, which increases the risk for a wide range of cancers due to a change in a tumor suppressor gene called TP53
• Hereditary breast and ovarian cancer syndrome (HBOC), linked to mutations in the BRCA1 and BRCA2 genes 
• Cowden syndrome, an inherited disorder that increases the risk of breast cancer, thyroid cancer, endometrial cancer and other types of cancer 
• Lynch syndrome, a cause of hereditary colorectal cancer, endometrial cancer and other cancers

Genetic variants have a high or low penetrance rate, which refers to its likelihood of causing a disease in most people who have it.

• A high-penetrance mutation may mean that most, if not all, family members with the variant may develop the cancer.
• A low-penetrance mutation suggests that fewer family members may develop the cancer.

Genes aren’t destiny. Other lifestyle factors also play a role in determining a person’s future risk for cancer.

What are acquired mutations?

Unlike hereditary mutations, acquired mutations occur at some point during a lifespan. These mutations aren’t present at birth, and only present in some cells. Because they occur in somatic cells, any cell of the body other than reproductive cells, acquired mutations may be called somatic variants. These can’t be passed down to offspring.

So, how do they occur? These mutations may occur when the person is exposed to something in the environment. For example, the sun’s damaging ultraviolet rays may harm DNA, causing changes that lead to skin cancer. Cigarette smoke, radiation, viruses and diet may also lead to acquired mutations that may affect cancer risk. Other acquired mutations may occur randomly as the cells divide, with no identifiable cause.

What are de novo mutations?

There’s another type of mutation or variant that occurs and may affect cancer risk: de novo (new) mutations. These are seen for the first time in a child—but neither parent. They may occur if a variant exists in the egg or sperm cell of one of the parents. A de novo variant may also arise spontaneously in the fertilized egg. It’s difficult to pinpoint exactly where a de novo mutation came from.

De novo variants are one explanation for genetic disorders that occur in a child, but not in his or her parents.

Testing for genetic mutations

It’s possible to find out if a person has genetic variants that increase the risk of some cancers before the cancer develops. This is known as predictive genetic testing. The decision to undergo this type of testing is personal, and typically based on personal or family history of cancer.

Some tests look for a single gene, while others look for harmful variants in multiple genes at the same time (panel testing). A genetic counselor should review all the potential risks and benefits of testing with the patient before a final decision is made.

The doctor takes a small sample of blood, saliva, cells from inside the cheek or even skin cells and sends them to a laboratory for analysis. The results of these tests may help the patient make informed decisions about screening and/or preventive treatment.

• A positive result means a variant was found, which suggests an increased risk for cancer.
• An uncertain result means that the test revealed a variant that is not yet well understood based on current research.
• A negative result means no variant was found. The person may still be considered to have an increased risk for cancer based on family history.

A genetic counselor can help to explain the significance of the test results.

Another type of genetic testing may be considered after the patient has been diagnosed with cancer to guide treatment decisions. Personalized medicine, also called precision medicine, looks at how a specific gene change may affect cancer risk and how the genes may affect treatment, according to the American Cancer Society. Personalized medicine may help eliminate some trial and error involved in choosing cancer therapies.

Anyone concerned about cancer risk due to family history or other factors should consider speaking with a genetic counselor.