Hereditary Cancers, Related Gene Mutations and Risk Management

What is hereditary cancer?

Cancer is a genetic disease at the cellular level: cancer cannot develop without genetic damage and its accumulation. However, being genetic and being inherited are not the same. In cancer, “genetic” and “hereditary” are often confused. All cancers result from genetic damage, but in about 10–15% of cancers this damage is passed down from parents; these are called hereditary cancers. In other cancers, genetic damage is not inherited but develops throughout life due to factors such as aging, smoking and obesity. These are called sporadic cancers.

Following completion of the Human Genome Project in 2003, most cancer-causing genetic mutations, or changes, were found to occur in body cells, also called somatic cells. These are known as somatic mutations and are not inherited by offspring. Less commonly, mutations in reproductive cells are passed to offspring and increase cancer risk. These are called germline or hereditary mutations.

From a genetic perspective, cancers are divided into three groups:

1. Sporadic cancers
2. Hereditary cancers
3. Familial cancers

We have explained the distinction between sporadic and hereditary cancers, but there is also familial cancer. Familial and hereditary cancers are often confused, although their underlying causes differ. Familial cancer means that the same cancer type occurs frequently within a family. For example, suppose breast cancer occurs in a person's family but genetic testing does not detect an inherited gene abnormality that increases that person's risk. If the person develops cancer, it is considered familial cancer. One example of familial susceptibility is why smoking causes cancer in some people but not others. DNA repair genes may not function as actively in these families as in others. However, recent research using more comprehensive genetic tests has shown that hereditary cancers are more common than previously estimated.

What is a hereditary cancer syndrome?

A hereditary cancer syndrome is an inherited condition associated with a higher-than-usual risk of certain cancers. These syndromes are caused by mutations in particular genes passed from parents to children. Certain cancer types may occur within families with a hereditary cancer syndrome.

Hereditary cancer syndromes share these three features:

• Several close relatives, such as a mother, daughter and sister, have the same type of cancer;
• Cancer develops at a young age; or
• Two or more cancer types develop in the same person.

Examples include hereditary breast and ovarian cancer syndrome, Li-Fraumeni syndrome, Cowden syndrome and Lynch syndrome. They are also called familial cancer syndromes and inherited cancer syndromes.

DNA damage and gene mutations

Cancer results from damage to DNA in your cells. These changes are called gene mutations. They can accumulate in cells over time. Cells with too many mutations may stop functioning normally, grow out of control and become cancerous. It can take many years for cells to accumulate enough damage to become cancer.

• Gene mutations that arise in cells throughout life and are not passed down from parents are called acquired or somatic mutations.
• Somatic mutations are caused by damage from wear and tear in genes over time.
• Aging and exposure to hormones, environmental toxins and certain viruses can cause mutations.
• Mutations passed from parents through reproductive cells, sperm and eggs, are called germline or hereditary mutations.

Genetic testing for hereditary mutations

Genetic testing for a hereditary mutation, also called germline genetic testing, examines DNA in blood or saliva samples to find mutations that may cause diseases such as cancer.

Genetic testing can help people understand their cancer risk, make medical decisions and take steps to reduce risk or detect cancer early. For people already diagnosed with cancer, it can help guide medical decisions about how best to treat their cancer.

How is genetic testing performed?

If you are considering genetic testing for hereditary cancers and wondering how to proceed, the following steps may help you make an informed decision and move forward with your plan.

• Know the signs of an inherited mutation
• Talk to a healthcare professional specializing in cancer genetics
• Read reliable sources of information on the subject
• Consider your personal circumstances
• Talk to your peers and learn about your family's medical history

Your personal circumstances may influence how and when you proceed with genetic testing.

• If you have a new cancer diagnosis or a recurrence, genetic testing may affect treatment decisions. You can use the information in this section on specific cancers and inherited gene mutations.
• If you have completed cancer treatment, genetic testing may help you understand the risk of a new or second cancer and influence decisions about screening and prevention.
• If you have never been diagnosed with cancer, genetic testing may clarify your risk and help you make decisions about screening and prevention.

In all situations, testing may provide your relatives with information about cancer risk and options for managing it.

Learn about cancer in your family

If you are considering genetic testing, learning your family's medical history can help you and your healthcare team determine whether testing would be useful and which test may be best for you.

Find out whether any relatives have had genetic testing. If a biological relative tested positive for an inherited mutation, ask them to share the laboratory report and any family medical history they can provide.

If you are the first person in your family to undergo genetic testing, you may need to begin collecting your family medical history from scratch. Try to gather information about close relatives diagnosed with cancer, their cancer types and their ages at diagnosis. Ideally, have this information ready for your genetic counseling appointment. Share it with relatives who also decide to have testing.

Important note: Testing for inherited mutations is increasingly available outside healthcare settings, without genetic counseling and sometimes without a doctor. Even if do-it-yourself testing options seem attractive, we recommend starting by talking to a specialist in cancer genetics.