Millions Have an Elevated Genetic Cancer Risk Because They Carry Pathogenic Variants or Changes In Their DNA Even Without a Family History. The One Thing To Do To Learn Your Risk

“Germline means we’re testing the DNA within the white cells or the buccal mucosa—the lining inside the mouth,” explains Dr. Jeff Jones, Professor of Urology at Baylor College of Medicine. “These are inheritable mutations, something that can be passed from one generation to the next.”

Understanding your family’s medical history plays a major role in determining whether testing is appropriate.

“Asking questions about what might be going on with your aunts, uncles, cousins, grandparents—that’s going to make the process much easier for your genetic counselor and physician,” says Rachel Webster, a genetic counselor at MD Anderson Cancer Center.

If cancer runs in your family, she adds, gathering as much information as possible is essential.

Kathy Baker, founder of the nonprofit My Faulty Gene, believes the true percentage of Americans with inherited cancer-related mutations may be even higher—especially for cancers with strong genetic links.

WATCH: How Testing For BRCA In Breast Cancer Works

Baker is a breast and ovarian cancer survivor and a BRCA gene mutation carrier, a gene change that significantly increases the risk of both diseases.

She discovered a lump at age 42, underwent a lumpectomy followed by chemotherapy and radiation, and was eventually told there was no evidence of disease.

RELATED: Myth Busting: Clearing Up Some Common Misconceptions About Genetic Testing

“When my oncologist suggested genetic testing because of my family history, I looked at him like he had horns,” she tells SurvivorNet. “I thought cancer was in my rear‑view mirror.”

Baker avoided testing for nearly a decade—until she learned about the Metcalfe study, which showed that a risk‑reducing mastectomy can dramatically lower the chance of developing breast cancer and significantly reduce mortality for women with BRCA1 or BRCA2 mutations. That evidence finally convinced her to get tested. When she learned she carried the BRCA mutation, she chose to undergo a preventive mastectomy.

A prophylactic mastectomy removes breast tissue before cancer develops.

“Risk‑reducing mastectomies are for women at very high risk—genetic mutation carriers who face the highest likelihood of developing breast cancer,” says Dr. Elisa Port, Chief of Breast Surgery at Mount Sinai Health System.

“There are really two options for women who test positive: high‑risk surveillance with mammograms and MRIs every six months, or taking a more proactive approach to actually prevent breast cancer by removing the tissue at risk,” Dr. Port adds.

Surveillance can help detect cancer early, Dr. Port notes, but it doesn’t prevent it.

“Early detection is a goal, not a guarantee,” she says. “For women who want to truly reduce their risk, removing the breast tissue is the only proven way.”

Some women decide to have their breasts reconstructed and have implants put in right after the mastectomy, while others don’t have reconstruction at all.

The benefits of a prophylactic or preventative surgery are:

• Significant reduction in cancer risk (from 80-90% to 1-2%)
• Nipples can often be spared
• Women can get reconstruction at the same time

“I know my risk, and I know I have a history of cancer, so I screen because knowledge is powerful,” Baker said.

A 2024 study published in Frontiers in Genetics on the prevalence of genetic testing among the general public found that “81% of Americans are aware of genetic testing and 40% have undergone at least one test, up from 75% awareness and 19% usage in 2020.”

“If I were in charge, we’d have universal testing, and everyone would know their genetic risk,” Baker said.

A cost-benefit analysis of population genetic testing published in 2023 in Annals of Internal Medicine concludes that genetic testing costs averaged $250 for a hypothetical all-in-one test limited to genes highly correlated with risk. More specifically, the study says people in their 30s, 40s, and 50s paid “$413, $290, and $166 respectively.”

“You can have self-initiated genetic testing, and programs exist for around $200 to $300 dollars. If you have a family member with a known mutation, generally the insurance will pay for it, which can be around $100,” Baker said.

Understanding Somatic Testing

Genetic testing looks for inherited mutations that raise a person’s risk for certain cancers, while somatic testing examines the DNA inside the tumor itself.

Somatic (non-inherited) mutation testing typically analyzes both blood and a sample of tumor tissue. That tissue usually comes from material collected during surgery or a biopsy and must be retrieved from the hospital or pathology lab where the procedure was performed.

Unlike germline mutations, somatic mutations are not passed down from parents—they arise spontaneously within cancer cells. For many patients, the original biopsy taken at diagnosis can be used for initial somatic testing.

Tumor genetics can also evolve over time, especially after multiple treatments. If the cancer progresses or becomes resistant to therapy, doctors may recommend repeating somatic testing with a new biopsy to guide next steps. National guidelines prefer using a fresh tumor sample whenever possible, but if obtaining tissue is unsafe or not feasible, a liquid biopsy—testing the blood for circulating tumor DNA (ctDNA)—can be used instead.

Genetic Testing’s Impact on Various Cancer Types

Breast and Ovarian Cancer Genetic Testing

About ten percent of breast cancers are hereditary, says Dr. Ophira Ginsburg, Director of the High-Risk Cancer Program at NYU Langone’s Perlmutter Cancer Center.

“When I meet with women who are at an increased risk for breast cancer because of BRCA mutations, I like to talk about the three options that they have for managing their risk,” says Dr. Freya Schnabel, Director of Breast Surgery at NYU Langone Medical Center. Those options are:

• Intensive surveillance: This means keeping an eye on your health, in an attempt to catch disease early if it does present itself.
• Medication: There are certain drugs available to lower the risk of developing breast cancer. But as with any medical treatment, risks and benefits must be considered.
  “Tamoxifen is the one we use in young women, and then aromatase inhibitors can also be used in post-menopausal women, who have been associated with lowered risk for developing hormone-sensitive breast cancer,” Dr. Schnabel tells SurvivorNet. “These medications have to be taken for five years, but have a meaningful reduction in the risk of developing breast cancer, especially for BRCA2 carriers,” Dr. Schnabel adds.
• Surgery: This is the option that will lower a woman’s chance of getting breast cancer as much as possible. It involves removing as much breast tissue as possible while attempting to preserve the nipple area, should a woman opt for breast reconstruction.

For those patients with ovarian cancer curious about genetic testing to determine their risk of mutations, doctors can either refer them to genetic counselors who can conduct thorough family histories to talk about the risks and benefits, and/or some doctors may discuss this with the patients themselves.

These types of tests are important as they can affect treatment choices and recommendations. For example, some patients may be better candidates for PARP inhibitors as maintenance or treatment.

“Basically, PARP inhibitors are forcing cancer cells — instead of repairing their DNA and continuing to persist and kind of hobbling along and continue to help that tumor grow and develop– PARP inhibitors cause those cancer cells to die,” explains Sheryl Walker, a genetic counselor at Genome Medical in Dallas, Texas. “It forces them down the path towards self-destruction essentially.”

WATCH: Should I Get Genetic Testing to Assess My Risk for Breast Cancer?

Ultimately, even though ovarian cancers with BRCA gene mutations tend to respond best to PARP inhibitors, many women without these mutations can also benefit from the drugs.

“The estimates are 90% of the individuals in the US who carry a BRCA gene don’t even know it until someone in their family gets cancer,” Dr. Beth Karlan, Gynecologic Oncologist at UCLA Medical Center, tells SurvivorNet.

“If the patient is found to carry one of these BRCA genes, every blood relative of hers has a 50/50 chance of having that themselves,” Dr. Karlan adds.

Genetic Testing In Prostate Cancer Care

“When you have a family history, uncles, parents, grandparents, these are all men, of course, because it’s prostate cancer, then those individuals can pass on these inheritable genes, and so we look at the germ line to see if one of those genetic mutations is present, and they can they can help us determine sensitivity to types of therapy,” Dr. Jeff Jones says.

Germline testing for inherited mutations in metastatic prostate cancer is always recommended and typically involves consultation with a genetic counselor and a saliva test, which is often covered by insurance but can cost up to $250 out of pocket, says Dr. Michael Carducci, a medical oncologist focused on prostate cancer research at Johns Hopkins Kimmel Cancer Center.

WATCH: Molecular Testing Can Help Create a Tailored Prostate Cancer Treatment Path

Germline testing for prostate cancer is growing rapidly, especially with an increase in precision medicine or targeted therapies.

Current national guidelines recommend that anybody diagnosed with metastatic prostate cancer should undergo genetic testing. When discussing prostate cancer as genetic or molecular testing, remember that there are two main categories: germline and somatic tumor testing. The costs and benefits of these tests can vary.

“Similar to other cancers, prostate cancer, we are utilizing germline BRCA1 and 2 testing in stage four prostate cancers. And those mutations can be treated with a PARP inhibitor,” explains Dr. Ankit Madan, a medical oncologist and hematologist at MedStar Southern Maryland Hospital Center.

WATCH: Genetic Testing’s Role In Prostate Cancer Care

“The only other genetic test we do for prostate cancer is checking for homologous recombination repair gene deficiency, for which a different Talazoparib PARP inhibitor in addition to Enzalutamide is used,” Dr. Madan adds.

Genetic Testing In Lung Cancer Care

“Today, when a patient comes in with lung cancer, the first thing we do is next-generation sequencing on the tumor,” says Dr. Ronald Natale, the director of the Lung Cancer Clinical Research Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center in Los Angeles.

WATCH: How Genetic Testing Determines Treatment in Lung Cancer

“We specifically search for hundreds of different mutations knowing and keying in on several mutations that we know that are common in lung cancer and for which we have new treatments that are highly effective, much more successful than chemotherapy, much less toxic, many of them in pill form that we can give patients so that within a matter of weeks their cancers undergo dramatic regressions and they’re restored to some good level of health at least for a period of time until their cancers ultimately become resistant,” Dr. Natale adds.

Dr. Natale adds that lung cancer patients are also tested for the production of PD-L1, a type of protein that blocks the immune system from attacking the cancer.

“Cancers that produce a very high level of PD-L1 have a very high chance of responding to treatment that targets PD-L1, about a 50% chance of a dramatic response. If we combine that immunotherapy with chemotherapy, the results are even better. 80% of patients will have a dramatic response,” Dr. Natale says.

Genetic Testing in Bladder Cancer Care

In some families, bladder cancer occurs at higher rates than in the general population. In these cases, careful examination of the genealogy may reveal specific mutations passed from parent to child that may lead a medical provider to suspect one of the hereditary forms of bladder cancer. Some germline mutations linked to bladder cancer include:

• BRCA1
• BRCA2
• MSH2
• CHEK2
• ERCC3

If genetic testing reveals you lack certain genes mutated in bladder cancer, you may be less likely to respond to certain treatments. These include targeted therapies, immunotherapies, and chemotherapy drugs.

WATCH: What Can Genetics Tell Us About the Molecular Features of a Bladder Cancer Tumor?

“Any patient who has stage 2 or greater bladder cancer, I strongly advocate for genetic testing,” Dr. Arjun Balar, medical oncologist and assistant professor of medicine at the Perlmutter Cancer Center at NYU Langone Health.

“Anywhere between 12 to maybe 15% to 16% of patients who have bladder cancer may harbor a mutation in a gene called FGFR3. That is an important gene that appears to be particularly important in bladder cancer and for which we have drugs. What we also know is that patients who have FGFR3 mutations with bladder cancer are actually less likely to respond to some of our standard-of-care immunotherapy drugs,” Dr. Balar adds.

What the Lynch Syndrome Tells Us About Colon Cancer Risk?

Although most colon cancer affects people with no family history or genetic predisposition to it, a small number of people do suffer from hereditary colon cancer. The most common of these is Lynch Syndrome, also known as Hereditary (Non-Polyposis) Colon Cancer. It’s estimated that this disease is responsible for 3% of all colorectal cancers.

WATCH: Cancer Risks Associated with Lynch Syndrome

 

If you have Lynch Syndrome, you have up to an 80 percent chance of developing colon cancer in your lifetime.

“Individuals who carry one of the genes that’s associated with Lynch syndrome can be offered testing, certainly screening, at a much earlier age than you normally would have suggested by your care provider, even as early as the age of 25. We also would screen with a colonoscopy much more frequently,”  Dr. Ophira Ginsburg, formerly a medical oncologist at NYU Langone’s Perlmutter Cancer Center and now a Senior Scientific Officer at the National Cancer Institute, tells SurvivorNet.

Estimated general lifetime cancer risks for people with Lynch syndrome:

• Colorectal cancer 20% – 80%
• Endometrial cancer 15% – 60%
• Ovarian cancer 1% – 38%
• Stomach cancer 1% – 13%
• Hepatobiliary tract cancer (liver/bile duct/gallbladder) 1% – 4%
• Urinary tract cancer (kidney, ureter, bladder) 1% -18%
• Small bowel cancer (intestines) 1% – 6%
• Pancreatic cancer 1% – 6%
• Brain 1% – 3%

WATCH: How Genetic Counselors Can Help?

Genetic counselors are available at many hospitals and related institutions to help patients navigate getting genetic testing.

Learn more about SurvivorNet's rigorous medical review process.

---