What causes cancer?

Cancer is caused by genetic changes, known as mutations or pathogenic (disease-causing) variants, in a cell. The mutations cause the cells to grow uncontrollably and develop into tumors. The mutations that can lead to cancer occur in genes that normally prevent tumors from growing when functioning properly. These mutations can be acquired throughout a lifetime and are caused by various risk factors including aging, environmental factors, and lifestyle factors.

What is hereditary cancer?

5-10% of cancer cases are associated with genetic mutations inherited from a parent and run in families. Families with an inherited mutation tend to have young-onset cancers (under the age of 50) and multiple family members diagnosed with cancer, typically involving multiple generations of family members.

A person who inherited a mutation has an increased risk to develop certain types of cancer. The risk for specific cancers is dependent upon which gene has a mutation. There are mutations in genes that increase the risks for more common cancers, such as breast or colon cancer. Other gene mutations may increase risk for more rare cancers, such as retinoblastoma. While there are many genes that, when mutated, cause an increased risk for breast cancer, mutations in the BRCA1 and BRCA2 genes are the most common hereditary cause of breast cancer. If you are concerned about a hereditary cancer syndrome based on your personal or family history of cancer, talk with your doctor or a genetic counselor.

What are the risks associated with mutations in the BRCA1 and BRCA2 genes?

People with inherited mutations in the BRCA1 or BRCA2 genes have an increased risk to develop breast, ovarian, and other cancers such as prostate, pancreatic, and melanoma. These individuals are said to have Hereditary Breast and Ovarian Cancer (HBOC) syndrome.

How are mutations in the BRCA1 and BRCA2 genes inherited?

• Individuals who carry a mutation in BRCA1 or BRCA2 inherited the mutation from one of their parents.
• The children, siblings, and parents of an individual with a BRCA1 or BRCA2 mutation each have a 50% risk to carry the same mutation. It is important that individuals with identified mutations discuss these risks with their family members.
• Individuals with a BRCA1 or BRCA2 mutation may never develop cancer, but can still pass the mutation on to their children who would still have an increased chance of developing cancer.
• Both men and women can inherit BRCA1 or BRCA2 mutations.
• Although the risk for cancers is higher in women who carry a mutation, men who carry BRCA1 or BRCA2 mutations can still develop cancer.
• As the cancers associated with BRCA1 or BRCA2 do not occur until adulthood, an individual can wait until adulthood to weigh the benefits, risks, and limitations of undergoing genetic testing.  Screening for cancers associated with BRCA1 and BRCA2 does not begin prior to adulthood. Therefore, testing of minors is not recommended.

How can carrying a BRCA1 or BRCA2 mutation impact healthcare decisions?

Carrying a BRCA1 or BRCA2 mutation may change how an individual should be screened or treated for cancer.

• Screening: Since individuals with BRCA1 or BRCA2 mutations are at an increased risk to develop certain cancers, specialized screening is recommended. This may include starting screening at younger ages than the general population and undergoing more advanced screening.  Specific recommendations can be made by a doctor or genetic counselor.
• Preventive (or Risk-Reducing) Surgeries: Individuals with BRCA1 or BRCA2 mutations may also choose to have surgeries, such as removing the breasts or ovaries, to greatly reduce the risk of developing cancer.
• Targeted Therapies: Individuals with BRCA1 or BRCA2 mutations who have already developed cancer may be eligible for specific targeted therapies as a treatment option.

Why would only a couple of mutations be tested?  Why is ancestry important, especially Ashkenazi Jewish ancestry?

In certain genes, there are specific mutations observed in higher rates among people of similar ethnic backgrounds. This happens when a group was geographically or culturally isolated, where one or more of the shared ancestors of that group was a carrier of the mutation and passed it to his or her descendants. These are often called founder mutations.

For the BRCA1 and BRCA2 genes, there are three common mutations found in people of Ashkenazi (Eastern European) Jewish descent. Although Judaism is a religion, Ashkenazi Jewish is an ethnic group. A person can have Ashkenazi Jewish ancestry whether or not his or her family identifies as Jewish. A person can also be Jewish by religion, but not genetically Jewish. One in 40 individuals of Ashkenazi Jewish descent carries one of these three founder mutations in BRCA1 and BRCA2, which is why patients with Ashkenazi Jewish ancestry are often offered a test that looks just at these three alterations.  However, a person with Ashkenazi Jewish ancestry can still have a different mutation in the BRCA1 or BRCA2 genes.

In addition, people without Ashkenazi Jewish ancestry are not likely to have one of these specific founder mutations. There are thousands of known mutations in BRCA1 and BRCA2. If a test only looked at these three specific mutations, it will miss anyone who has any other mutation within BRCA1 or BRCA2, and can incorrectly identify someone as negative when they are actually positive.

For this reason, ancestry may impact the appropriate genetic testing to consider, so it is helpful to know and share this information, when available.  Specific to BRCA1 and BRCA2, more comprehensive genetic testing beyond these three founder mutations may be indicated.  A consultation with your doctor and/or genetic counselor can help you determine which testing is right for you and/or confirm that the appropriate testing was completed.  

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