Is hereditary cancer risk smoldering in your genes?

Hereditary cancer risk can be passed down among generations, just like physical characteristics that we can identify in our children or parents. In all, there are more than 50 hereditary cancer syndromes. Most cancers are not hereditary – they occur at random, associated with risk factors such as natural aging, environmental factors, or lifestyle choices, like smoking or excessive alcohol use. Only 5% to 10% of cancer cases are hereditary.

Hereditary cancer risk is passed from parent to child through genes, in the code called DNA. Some of our genes are meant to protect the body from developing cancer. A harmful change in a gene meant to protect the body from developing cancer is called a pathogenic variant or mutation. The gene won’t work correctly, possibly failing to protect an individual from cancer. The result is that the person is at increased risk of developing cancer during their lifetime. That individual has a hereditary cancer syndrome.

It’s important to note that a person with a hereditary cancer syndrome inherits an increased risk of developing cancer. It is not at all a certainty that a person with a hereditary cancer syndrome will get cancer. The risk for cancer in each syndrome varies.

One of the better-known hereditary cancer syndromes is hereditary breast and ovarian cancer (HBOC) syndrome. Two pathogenic variants, BRCA1 and BRCA2, are associated with HBOC syndrome, causing an increased risk for cancer of the breast, ovaries, fallopian tubes, prostate, and pancreas. Another hereditary cancer syndrome is familial adenomatous polyposis (FAP) syndrome, with increased risk for developing multiple colon polyps and cancer in the colon and rectum, small intestine, stomach, pancreas, thyroid, brain, and liver.

People with a hereditary cancer syndrome may get cancer at a young age or get more than one cancer. Family members may have the same cancer or a related type of cancer. That’s because relatives have some of the same DNA and inherited the same pathogenic variant.

Genetic testing can help determine if a person has a hereditary cancer syndrome. It is recommended for people with:

• A personal history of cancer diagnosed before age 50
• A family history of cancer before age 50
• Two or more cancers in one person
• The same cancer in two or more close relatives
• An unusual presentation of cancer (such as breast cancer in men)
• Certain ancestral backgrounds (including Ashkenazi Jewish heritage)

Even the same cancer in multiple family members doesn’t always mean there is a hereditary cancer syndrome in the family. They may share other risk factors, such as smoking, or toxin exposure. The following are risk factors suggesting that a person may have a hereditary cancer syndrome.

• Having cancer at a younger age (before age 50) than usual in the population
• Two or more cancers in the same part of the body, different parts of the body, or in paired organs (e.g., both breasts or kidneys)
• A cancer occurs in a person whose sex is not commonly affected (e.g., breast cancer in males)
• Two or more first-degree relatives (parents, siblings, children) with the same cancer, a rare cancer, or cancers known to be part of a hereditary cancer syndrome

Genetic Testing

Genetic testing looks for genes associated with hereditary cancer syndromes. It’s usually performed on blood or saliva samples in which the DNA is examined for pathogenic variants. Usually, several genes within the sample are examined, which is called “panel genetic testing.”

There are three possible test results:

• Positive: A pathologic variant is present that increases the risk of developing certain cancers. The person may be offered cancer-specific screening or strategies to reduce their cancer risk. Family members are at risk for the same pathogenic variants and may want to consider testing.
• Negative: No pathogenic variants were found in the sample. Cancer screening and risk-reducing recommendations are then based on personal and family history.
• Variant of uncertain significance (VUS): This means a variant was found but it isn’t known if it is associated with an increased risk for a certain cancer, or a benign variant not associated with an increased risk for cancer. (Most are later classified as benign.) Recommendations for cancer screening and risk reduction are based on personal and family history.

People who have a positive result should talk to a genetic counselor or healthcare provider with expertise in hereditary cancer syndromes for recommendations regarding increased, specific, cancer screening and risk-reduction strategies.

Examples of hereditary cancer syndromes

According to Yale Medicine, more than 50 hereditary cancer syndromes have been identified. Examples include:

• Hereditary Breast and Ovarian Cancer (HBOC) syndrome
• Lynch syndrome
• Familial adenomatous polyposis (FAP) syndrome.
• Li-Fraumeni syndrome (LFS)
• Peutz-Jeghers syndrome (PJS)

As mentioned, having a hereditary cancer syndrome doesn’t necessarily mean that an individual will go on to develop cancer. It’s always a good idea to talk to your doctor about your family history and potential risks, along with options for genetic testing.