Genetic testing for hereditary cancer (BRCA, Lynch syndrome, and more)

There are two completely different kinds of cancer genetic testing, and confusing them is one of the most common mistakes patients and even some clinicians make.

• Tumor (somatic) testing looks at the cancer itself to guide treatment. This is what produces biomarkers like EGFR, HER2, MSI — see our biomarker guide.
• Germline testing looks at the DNA you were born with, usually via a blood or saliva sample, to see if you have an inherited mutation that raised your cancer risk — and may raise the risk for your family members.

This guide is about germline testing.

Who should consider germline genetic testing

Major guidelines (NCCN, ASCO) recommend germline testing when any of the following apply:

Cancer diagnosis patterns

• A personal history of breast, ovarian, pancreatic, prostate (high-grade or metastatic), or colorectal cancer
• Breast cancer diagnosed under age 50
• Triple-negative breast cancer at any age
• Male breast cancer
• Ovarian cancer at any age
• Pancreatic cancer at any age
• Colorectal cancer diagnosed under age 50, or with certain pathology features
• Multiple primary cancers in one person
• Rare cancers at young ages (sarcoma, adrenocortical, medullary thyroid, etc.)

Family history patterns

• Multiple close relatives with the same cancer or related cancers
• Cancer in multiple generations on the same side of the family
• Male relatives with breast cancer
• Ashkenazi Jewish ancestry plus any of the above cancers
• A known inherited mutation in the family

When doctors recommend it without asking

At many major centers, all patients diagnosed with ovarian, pancreatic, or metastatic prostate cancer are offered germline testing regardless of family history, because the yield is high enough.

What the tests look for

The most commonly tested genes for cancer risk include:

BRCA1 and BRCA2 — The best-known. Mutations raise lifetime risk of breast cancer to 50-70%, ovarian cancer to 15-40%, and also raise pancreatic and prostate cancer risk. BRCA-mutated cancers often respond to PARP inhibitors.

Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM) — Raise lifetime risk of colorectal cancer to 50-80%, endometrial cancer to 40-60%, and also raise risk of ovarian, gastric, small bowel, urinary tract, and other cancers. Lynch-associated tumors are usually MSI-H (respond to immunotherapy).

PALB2 — Breast, ovarian, and pancreatic cancer risk. Often tested with BRCA.

TP53 (Li-Fraumeni syndrome) — Multiple early-onset cancers across many sites. Rare but serious; management includes intensive surveillance.

CDH1 — Diffuse gastric cancer and lobular breast cancer risk.

PTEN (Cowden syndrome) — Breast, thyroid, endometrial, kidney cancer risk plus benign features.

APC — Classical familial adenomatous polyposis (FAP); very high colorectal cancer risk.

CDKN2A — Melanoma and pancreatic cancer risk.

Many others — Modern panels test 50-100+ genes at once. Your counselor picks the right panel.

How the testing works

Step 1 — Genetic counseling (strongly recommended before testing)

A genetic counselor reviews your personal and family history, explains which genes are worth testing, explains what positive/negative/uncertain results would mean, and helps you think through the implications before you order the test. Many insurance plans require a counseling visit for coverage.

Find a counselor: NSGC directory, or ask your oncology team for their recommended counselor.

Step 2 — Sample collection

Usually a saliva kit or a blood draw. Most results return in 2-3 weeks.

Step 3 — Results review with the counselor

Results come back as one of:

• Positive — a pathogenic or likely pathogenic mutation was found
• Negative — no mutation found
• Variant of Uncertain Significance (VUS) — a genetic variant was found, but we don’t yet know if it affects risk. VUSes are usually not acted on clinically. Some are reclassified later as new data comes in.

The counselor explains what the result means for you, for your family, and what surveillance or risk-reduction options exist.

What happens with a positive result

Depends on the gene. For BRCA1/2 as an example:

For you (if you already have cancer): Treatment may change — PARP inhibitors become an option. You may be eligible for additional trials. Surveillance for other at-risk cancers (e.g., contralateral breast, pancreatic) may be added.

For you (if you don’t have cancer yet): Enhanced screening (MRI breast imaging, earlier colonoscopy schedule, etc.) and/or preventive options (prophylactic surgery in some cases) are discussed with your team.

For your family: First-degree relatives (parents, siblings, children) each have a 50% chance of having inherited the same mutation. A positive result lets them decide to get tested (usually after counseling), which can unlock early screening for them.

Cost and insurance

• Most insurance plans cover germline testing when guidelines-based criteria are met (that’s why counseling matters — the counselor documents the indication).
• Self-pay rates have dropped dramatically. Many labs now offer comprehensive panels for $250-$500 self-pay. 23andMe’s medical-grade report is not a substitute for clinical genetic testing; do not rely on direct-to-consumer tests for treatment decisions.
• Patient assistance programs exist for uninsured patients (ask your counselor or see financial aid resources).

Common misunderstandings

“My direct-to-consumer test was negative, so I’m fine.” No. Consumer tests look at a limited set of mutations. A clinical panel looks at hundreds to thousands of mutations across dozens of genes. A consumer “negative” does not rule out hereditary risk.

“No one in my family had cancer, so I don’t need testing.” Family history is suggestive but not required. Some mutations arise spontaneously, and family histories can be incomplete (small families, estranged relatives, undocumented cancer deaths). Guidelines now include diagnosis-based criteria (e.g., any pancreatic cancer, any ovarian cancer, any male breast cancer) regardless of family history.

“I’m an adopted child so testing won’t help me.” Testing is not about family history — the genetic result stands on its own. Adopted patients benefit just as much.

“I don’t want to know.” That’s a legitimate choice. You don’t have to test. A counselor can walk through the pros and cons of not testing too. The decision is yours.

Privacy and discrimination

The Genetic Information Nondiscrimination Act (GINA) of 2008 prohibits health-insurance and employment discrimination based on genetic information. GINA does not cover life, disability, or long-term-care insurance. For many patients this isn’t an issue; for some, it’s worth thinking about before testing (some people purchase those coverages before testing).

Related on CancerDrs

• Cancer biomarkers explained (tumor / somatic testing) — different from germline testing, but often done in parallel
• How to read a pathology report
• Questions to ask your oncologist
• Financial aid resources