Inherited cancer gene mutations - Implications for families

With genetic testing becoming more common in cancer patients this article adapted from Lab Tests Online US explains the use of cascade testing to detect inherited cancer gene mutations.

Increasingly, patients diagnosed with certain types of cancer will be offered genetic testing to see whether they have inherited a gene alteration (mutation) that causes an increased risk for the cancer. Although inherited cancer gene mutations account for a relatively low percent of all individuals with cancer, people who test positive for a cancer gene mutation have a significantly increased risk of developing cancer compared to individuals who do not have an inherited cancer gene mutation.

When an individual is found to have inherited a cancer gene mutation, it also means that their blood relatives (e.g., parents, siblings or children) could also have inherited the same mutation and be at increased risk of developing cancer. For any "at-risk" family members, genetic counseling is recommended to discuss the benefits, risks and limitations of genetic testing. At-risk family members may opt to have blood testing done to determine whether they too have the familial cancer gene mutation. This process of testing the blood relatives of an individual who is found to have an inherited cancer gene mutation is known as "cascade" testing.

Recently, the American College of Obstetricians and Gynecologists (ACOG) became one of the first medical associations to advise doctors to discuss cascade testing with their patients, issuing a new Committee Opinion in January. According to ACOG, "cascade testing protocols and interventions may save lives and improve health and quality of life for [affected] family members." Relatives who learn they have an affected family member have more choices about their health care, including whether to undergo genetic counseling and testing themselves. Individuals who discover that they have inherited a known cancer gene mutation have options to help manage their increased risk of developing cancer. This may include more frequent or improved methods of screening that can detect cancers earlier, before signs and symptoms appear, when they are most treatable.

Although inherited mutations in cancer genes are only estimated to account for between 5% to 10% of all individuals with cancer, it is important to identify these individuals, as they have a much higher lifetime risk of developing cancer than individuals in the general population. For example, women with an inherited mutation in the BRCA1 or BRCA2 gene have approximately a 70% chance of developing breast cancer at some point during their life, compared to the average woman's lifetime risk of just 12%. Lynch syndrome is another type of hereditary cancer predisposition syndrome. Individuals with Lynch syndrome have an increased risk for a number of different types of cancer, but the biggest risk is for colon cancer. An inherited mutation in one of the Lynch syndrome genes is associated with about a 50 to 80% lifetime risk of developing colon cancer, compared to a general population lifetime risk of about 4 to 5%.

When obtaining a medical history, healthcare practitioners often ask patients if they have any blood relatives who have had cancer and whether their relative was tested for any cancer gene mutations. Conversely, healthcare practitioners will talk to those patients who have been found to have an inherited cancer predisposition syndrome about alerting family members who may also have inherited the familial mutation to help guide them through the genetic counseling and testing process.

For any patient whose relative has informed them that they may also be at risk of carrying an inherited cancer gene mutation, ACOG recommends the healthcare practitioner obtain documentation (such as a genetic counseling letter or a genetic test report) from the relative's physician in order to confirm the specific genetic mutation and ensure appropriate risk assessment and accurate testing. ACOG also recommends that no testing take place until after a patient considering testing has received genetic counseling about what the testing may show, how that may impact the patient’s healthcare, and has specifically indicated that they wish to be tested.

"Most importantly, we must help patients navigate what is often a complex and emotional process," says Kristen Matteson, MD, MPH, an associate professor of obstetrics and gynecology at Brown University in Rhode Island and head of the ACOG committee that wrote the recent recommendations. "Patients may be confused by their own diagnosis or what it means to receive a letter informing them of a relative's diagnosis. It's vital that obstetrician-gynaecologists are prepared with information and resources to help women make informed and timely choices about available options and the appropriate next steps if further testing is desired."

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