Kari Bohlke, ScD
What characteristics have you inherited from your family? Specific features such as hair and eye color may come to mind, along with less tangible characteristics, like a quirky sense of humor.
Sometimes, however, it’s hard to predict which parts of our family history will play out in our own lives. Take cancer: your family history can provide clues about your own risk, but often doesn’t tell the whole story. Cancer can develop in someone with no family history of the disease, and may never develop in someone with a strong family history.
Fortunately, research into inherited susceptibility to cancer is helping to reduce this uncertainty for some families, allowing individuals to make informed choices about how to manage their cancer risk. In these families, certain members have a very high risk of cancer as a result of genetic mutations that are passed on from one generation to the next. These mutations tend to result in multiple family members developing cancer, often at a relatively young age.
As an example, mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family. Similarly, inherited mutations in one of three genes—MLH1, MSH2, or MSH6—lead to a condition known as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC). People with Lynch syndrome have an increased risk of colorectal cancer, uterine cancer, and ovarian cancer, as well as other cancer types.
For these and other well-established hereditary cancer syndromes, genetic testing can determine which family members have inherited the mutation and which haven’t. People who find out that they have a mutation that places them at high risk of cancer can take steps to reduce their risk or to detect the cancer at the earliest stage possible.
“It’s the kind of information that really can drive patients or family members in terms of medical decision-making going forward,” says Donald Braun, PhD, Vice President of Clinical Research at Cancer Treatment Centers of America® (CTCA) in Zion, Illinois. “People who discover that they have these mutations are now in a much more informed position to make choices about how they will manage their health.”
In the case of BRCA1 or BRCA2 mutations, for example, options for risk reduction or early detection include prophylactic (preventive) surgery to remove the breasts or ovaries before cancer develops, chemoprevention (use of medication to reduce cancer risk), and earlier and more frequent screening.
Who Should be Tested?
Your doctor or a genetic nurse or genetic counselor can help you determine whether you are a candidate for testing. Genetic testing is not recommended for everyone; it’s targeted toward those who are most likely to have a certain mutation. Risk of having a mutation is based on your own medical history as well as your family’s medical history. Aspects of family history that are helpful to collect include which family members have cancer as well as which family members do not have cancer. If you are considering genetic testing, try to collect information about any family members who have been diagnosed with cancer, including age at diagnosis and site of cancer (breast, for example). In some cases, it’s also helpful to have information about your family’s ethnic origins; certain BRCA1 and BRCA2 mutations, for example, are particularly common in people of Ashkenazi Jewish descent.
What Are the Possible Test Results?
Understanding the results of a genetic test for cancer susceptibility can be complicated. “There are four possible results,” explains Marty Weinar, MS, RN, manager of Research and Genetics at CTCA in Philadelphia, Pennsylvania. A positive test is the most straightforward: it means that you have a gene mutation that is known to increase cancer risk. A positive test does not mean that you will definitely get cancer; rather, the positive test means that you are more likely to develop cancer than a person without the mutation.
Interpretation of a negative test will depend on whether or not a specific gene mutation has already been identified in your family by previous testing. If your family has a known mutation and you test negative, it’s a true negative: you have not inherited your family’s known cancer susceptibility gene. Keep in mind that a negative test does not mean that you are immune to cancer. It simply means that you don’t have the very elevated risk that your affected family members have.
If you test negative and there is no known gene mutation in your family, the result is referred to as a negative of limited significance. With this result, says Weinar, “we can’t say with absolute certainty that there is not a mutation; you just don’t have what we were able to test for.”
A final possibility is that the test will identify a genetic change that has an unknown effect. This is referred to as a variant of uncertain significance. Although this can be a disconcerting result to receive, “it happens less frequently than it used to,” says Weinar. “We tell these patients to stay tuned.” If the genetic change is later found to be harmless (or if it’s found to increase cancer risk) patients can be informed.
The Benefits of Working with a Genetics Professional
Health care providers with specialized training in genetics can help you navigate and understand all stages of the testing process. These providers include genetic counselors and nurses trained in genetics. “The role for the nurse or the counselor,” says Weinar, “is to identify which patients might be appropriate for testing, educate and counsel the patients, get all the paperwork filled out, and then, depending on the results, collaborate with the doctor to come up with a plan for managing the cancer risk.”
“Susceptibility testing should never be done without the counselors and the practitioners who can tell you what the results mean and what options are available to help you manage your risk,” emphasizes Dr. Braun. “The message should not be, ‘I have horrible news: you have the mutation and there’s nothing you can do about it,’ because that’s not true. If you have the mutation, you’re armed with some very powerful information. In the right setting, qualified practitioners and counselors can truly help you make decisions that can save your life.”
