What is Cascade Testing for Hereditary Cancer Syndromes?

The term “cascade testing” refers to a strategy of genetic testing for hereditary cancer syndromes—predispositions to cancer that run in families because of an inherited gene mutation. Overall, inherited mutations are thought to play a role in about 5 to 10 percent of cancers.

Cascade testing is an efficient way of tracking inherited cancer predisposition mutations in families. It can save lives and improve health and overall quality of life, as it allows clinicians to tailor interventions based on whether or not someone is known to carry risk for inherited cancer.

Cascade testing begins when a person is diagnosed with a familial cancer predisposition syndrome or a cancer that is likely to have been caused by an inherited mutation. Testing, through analysis of a blood or tissue sample, can reveal if the individual carries a known predisposition mutation.

Further testing then proceeds with close relatives such as parents and children and then extends to extended family such as aunts, uncles and cousins in a stepwise, cascade fashion until all at-risk relatives have been screened to determine if they do or do not carry an inherited cancer-risk mutation.

Sapna Syngal, MD, MPH, of Dana-Farber's Center for Cancer Genetics and Prevention.
Sapna Syngal, MD, MPH, of Dana-Farber’s Center for Cancer Genetics and Prevention.

Individuals who have not been diagnosed with cancer, but who are found to carry an inherited cancer risk mutation, can be offered close monitoring, including tests (such as colonoscopies) at an earlier age than would be recommended for someone at average risk. Those who learn they did not inherit a cancer risk mutation are spared unnecessary medical interventions and worry. Other preventive measures, such as removal of precancerous lesions or lifestyle changes, could also be suggested on an individual basis.

Some examples of inherited cancer syndromes are hereditary breast cancer and ovarian cancer syndrome, which is caused by mutations in BRCA1 and BRCA2 genes; Li-Fraumeni syndrome, caused by mutations in the TP53 tumor suppressor gene; Lynch syndrome, the results of mutations in any of several genes; Cowden syndrome, caused by PTEN gene mutations; and familial adenomatous polyposis, which results from mutations in the APC gene.

An upcoming new study involving cascade testing called GENERATE—GENetic Education, Risk Assessment, and TEsting—will revolve around people who have a close relative with pancreatic cancer that was caused by an inherited gene mutation. About one in 10 patients with pancreatic cancer carry such a gene, which can be passed down through their family. Cascade testing in the close relatives of these pancreatic cancer patients can identify individuals who harbor the gene mutation and therefore are at increased cancer risk. They will benefit from learning about the risk and can take advantage of options for early or more frequent screening to look for cancer or pre-cancer. The hope is that with the predictive ability of genetic testing, the right screening can be offered to the right people, at the right time.

Learn more about genetic testing from Dana-Farber Cancer Institute.