Cascade Genetic Testing for Relatives

The Centers for Disease Control and Prevention defines it simply. Cascade testing is telling family members about a genetic condition found in the family, and then those relatives getting tested for it.

The word cascade describes the shape. One confirmed result in one person opens a path to their closest relatives. Whoever tests positive opens a path to theirs. It moves outward, one step at a time.

It only works when one thing is true first: someone in the family has a confirmed harmful variant, with a laboratory report to prove it.

If nobody in your family has been tested yet, the order matters.

CDC advises that the first person tested should, whenever possible, be someone who has had a related cancer. For hereditary breast and ovarian cancer, that means a relative who has had breast, ovarian, or another BRCA-related cancer.

The reason is practical. Testing an affected relative is the most likely way to find the variant that runs in the family. If you test a healthy relative first and the result is negative, you have learned almost nothing. The variant might still be in the family, just not in that person.

Once the variant is confirmed, testing the rest of the family becomes far simpler and much more informative.

CDC states that your children, sisters, brothers, and parents are most likely to share the same genetic condition, and that testing should start with them. These are your first-degree relatives.

CDC attaches one limit to that. Genetic testing for adult-onset conditions is not generally done in children. A child who would not act on the result for thirty years is usually better tested as an adult, when the decision is theirs. Ask the genetics service where the line sits for your family's condition.

For hereditary breast and ovarian cancer, CDC gives the figure directly. Your parents, children, sisters, and brothers each have a 1 in 2 chance, or 50%, of carrying the same variant.

The cascade then follows the side of the family it came from. CDC gives a clear example: if testing shows your mother has the same change you do, your mother's side gets tested. Your father's side does not need to be.

That saves people from testing that cannot help them.

This is where families most often go wrong.

Cascade testing is targeted. The laboratory looks for one specific variant, the exact one found in your relative. To do that, it needs the exact details.

"My aunt had the breast cancer gene" is not enough. BRCA1 and BRCA2 each contain thousands of possible changes. A general panel is not the same test, and it can produce a misleading result.

Get a copy of the actual laboratory report. It should name the gene, the exact variant in the lab's own notation, the laboratory, and the date. Send that report with the referral.

If the report cannot be found, ask the genetics service how to trace it. Laboratories keep records, and relatives can request their own copies.

A negative result is only meaningful when the family's specific variant was tested for and not found. Genetics teams call that a true negative.

CDC states that if a variant has been found in another family member and your test shows you do not have it, you are not at higher risk than the average person for breast or ovarian cancer. It also notes you cannot pass that variant on to your children.

NCI adds an important caution. A true negative does not mean no cancer risk at all. It means your risk is probably about the same as anyone else's.

So keep your routine screening. Mammograms, colonoscopy, and the rest still apply on the normal schedule. A negative result removes a specific extra risk, not every risk.

If the family variant was never identified, your negative result cannot be read that way. It is uninformative, and your care should still follow your family history.

A variant of uncertain significance is not a confirmed finding, and it is not a basis for testing the family.

CDC states this plainly in its Lynch syndrome guidance: family members usually should not be tested until doctors work out whether the uncertain variant causes cancer.

Testing relatives on an uncertain result gives them worry and no information. Wait for reclassification.

Here is the part people do not expect: the telling is yours to do.

CDC describes the first step in cascade testing as letting your family members know about your diagnosis and your test results. Your genetics service will help you. It will counsel you, and many services will draft the letter. But it will not contact your relatives for you. Your results are your medical record, and the approach has to come from you.

You are not obliged to do this perfectly, and you are not obliged to persuade anyone.

Things that make it easier:

• Ask the genetics service for a family letter. Many will write one that explains the finding, names the variant, and tells relatives what to ask for. You forward it. You do not have to explain the genetics yourself.
• Tell people separately rather than at a family event. This lands differently on different people.
• Say what you want from them. "I am not asking you to test. I am asking you to have the information."
• Give them a route: the genetics service name, the lab report, and the suggestion of a genetic counselor.
• Say what it changes. Screening earlier, more often, and sometimes options to lower risk. That is the point of knowing.

Expect delay. People take months or years. That is normal, and it is not a rejection of you.

CDC advises respecting a relative's decision not to test, while noting you can still offer them information to keep.

NCI states that health insurance typically covers genetic counseling and genetic tests that are considered medically necessary. Targeted testing for a known family variant is generally a much smaller test than a full panel.

NCI also recommends genetic counseling before any genetic testing for inherited cancer risk, and often after it as well.

One warning about consumer kits. NCI notes that as of January 2024 the only FDA-approved direct-to-consumer test for inherited cancer risk covers three BRCA variants, and that this approach misses about 80% of cancer-causing BRCA variants. A consumer kit is not a substitute for cascade testing.

Relatives worried about insurance or work should read about GINA, the federal law on genetic discrimination, before deciding. It protects more than people expect in some areas and less than they expect in others.

• About Cascade Testing — Centers for Disease Control and Prevention
• Genetic Testing for Hereditary Breast and Ovarian Cancer — Centers for Disease Control and Prevention
• Genetic Testing for Lynch Syndrome — Centers for Disease Control and Prevention
• Genetic Testing for Inherited Cancer Susceptibility Syndromes — National Cancer Institute
• Cancer Genetics Overview (PDQ) — National Cancer Institute