BRCA1 and BRCA2: What a Positive Result Means

What BRCA1 and BRCA2 do

BRCA1 and BRCA2 are genes that make proteins involved in repairing damaged DNA. Everyone has two copies of each, one inherited from each parent.

A harmful variant, also called a pathogenic variant or mutation, weakens that repair system. Most carriers still have one working copy, which is enough to protect cells. Cancer can develop when a cell later loses or damages that remaining copy.

That is why carriers tend to develop cancer at younger ages than the general population, according to the National Cancer Institute (NCI).

How common are harmful variants?

NCI puts the general-population rate at about 0.2% to 0.3%, roughly 1 in 400 people. In people of Ashkenazi Jewish descent it is about 2%, usually one of three founder variants.

Founder variants have also been found in Norwegian, Dutch, Icelandic, Hispanic, West African, African American, Sephardi Jewish and Bahamian populations, among others.

Cancer risks by gene

The table below uses lifetime risk estimates from NCI's BRCA fact sheet, last reviewed July 19, 2024. Ranges reflect differences between studies. They are population averages, not personal predictions.

Two patterns stand out. BRCA1 carries a much higher ovarian cancer risk. BRCA2 carries more of the risk for prostate, pancreatic and male breast cancer.

NCI also notes that BRCA1-related breast cancers are more often triple negative, a type that is harder to treat. Possible links to melanoma, stomach cancer and a type of uterine cancer are still under study.

Why consumer tests check so few variants

Consumer BRCA reports look for a preselected list of variants rather than reading every letter of both genes. That approach can catch common founder variants, but BRCA1 and BRCA2 have a very large number of different harmful variants.

The CDC says more than 1,000 BRCA mutations are known. On March 6, 2018, the FDA authorized 23andMe's BRCA report, which then checked only 3 of them. Those three are most common in people of Ashkenazi Jewish descent.

In August 2023, 23andMe announced FDA clearance to expand the report to 44 variants. Its product page still says these do not represent most BRCA variants in most ethnicities and do not cover other hereditary cancer genes.

Clinical testing ordered by a clinician can look far more broadly, often across the full genes and other cancer genes at once. Our comparison of hereditary cancer panels and whole genome sequencing explains the trade-offs.

Raw data and third-party tools

Some people upload raw consumer data to third-party sites that flag BRCA variants. NCI warns that such interpretation tools are prone to inaccuracy. A flagged variant from raw data needs clinical confirmation just like any other consumer result.

Confirming a positive result

Consumer labs are not required to follow the federal CLIA lab rules that clinical labs must meet, according to NCI. That is one reason a consumer BRCA finding should be repeated before it drives any medical decision.

1. Do not act on the consumer result alone. 23andMe's own clearance announcement says results should be confirmed by an independent test prescribed by a healthcare provider.
2. Book a doctor or genetic counselor. Bring the report and a written family history. Our guide on bringing DNA results to your doctor covers what to prepare.
3. Get a clinical test. A clinician can order testing from a clinical lab. It may confirm the specific variant or run a broader panel.
4. Read the result type. The CDC sorts results into positive, negative and variant of uncertain significance (VUS). NCI says most VUS results are later reclassified as benign, so manage risk on family history until then.
5. Make a plan. If confirmed, your clinician can set up a screening and prevention schedule and tell you which relatives to notify.

If a relative has had a BRCA-related cancer, the CDC says that person should ideally be the first in the family tested. A known family variant makes everyone else's results clearer.

What carriers can do

Management depends on sex, age, family history, plans for children and personal preference. Guidelines from the National Comprehensive Cancer Network (NCCN) are the main U.S. reference. The summary below comes from FORCE, a hereditary cancer nonprofit, which summarizes current NCCN guidance.

Surgery and medication

Risk-reducing mastectomy lowers breast cancer risk by about 90%, FORCE reports, but it has not been shown to improve survival. Removing the ovaries and fallopian tubes lowers ovarian cancer risk. NCI notes that all such surgeries are irreversible and carry real harms, including early menopause.

NCI says there is no proven effective screening for ovarian cancer, which is why surgery timing gets so much attention. Medications such as tamoxifen are FDA approved to lower breast cancer risk in high-risk women, but NCI says their benefit in BRCA carriers is not yet clear.

If you already have cancer

A BRCA variant can affect treatment. NCI lists several PARP inhibitors approved for certain cancers with BRCA changes. A tumor test that finds a BRCA change should prompt a conversation about germline testing to see if it was inherited.

Telling and testing relatives

Testing relatives for a known family variant is often called cascade testing. It is one of the most useful things a positive result can lead to.

• Children: each has a 50% chance of inheriting the variant, the CDC says.
• Parents and siblings: are among the relatives most likely to share it.
• Wider family: aunts, uncles, nieces, nephews and cousins are also at higher risk.

Relatives should be tested for your specific variant, so share a copy of your clinical report. The CDC notes that testing is usually not recommended for children, and NCI says professional groups do not recommend BRCA testing under 18.

The CDC's free My Family Health Portrait: Cancer tool can help you record family history before those conversations. A genetic counselor can help decide who to tell first and how. Our explainer on whether you need a genetic counselor covers when that help is worth booking.

Insurance protections

The Genetic Information Nondiscrimination Act protects against genetic discrimination in health insurance and employment. NCI notes it does not cover life, disability or long-term care insurance, or members of the military.