From Family History to Personal Prevention: Genetic Testing in Action

By Dr. Georgine Nanos, MD, MPH | Board-Certified Family Physician, Kind Health Group, Encinitas, CA

When people ask me what we actually do for cancer prevention here, I rattle off the list, the imaging and the blood work and the screening schedule, and the one that gets the least airtime is the one we only do once.

On the podcast I described it the way I describe it in the exam room. An Invitae genetic test, one time, looking at your own genetics to see what genetic risk you may be carrying, and then we build around what it shows us.

Once. And it can change the whole plan.

Your Family History Is Only as Good as What Your Family Told You

I am a family doctor, so of course my favorite diagnostic tool is a nosy question about your aunt. Who had cancer, what kind, how old were they. I ask it at every new visit and I will keep asking it, and I also know exactly how much it misses.

When Dr. Sonia Ramamoorthy, Chief of the Division of Colon and Rectal Surgery at UC San Diego, sat down with me on The Kind Revolution, she said colorectal cancer is one of those diseases families do not talk about, not even at the dinner table, and she also said that the people walking into her clinic used to be in their sixties and seventies and now they are in their thirties and forties.

Put those two things together and you see the problem. The family history you give me is the family history your family was willing to say out loud. Grandma had "stomach trouble." An uncle died young of "something with his liver." A cousin had surgery nobody explained. I can work with a family rumor, and I will, but I cannot build a cancer plan on one.

And families are small now, and people are adopted, and people are estranged, and people move across the country and lose track of who had what. A thin family tree does not always mean a safe one.

What Genetic Testing Actually Looks For

Genetic testing for cancer risk looks for specific inherited changes in your genes, the kind you got from a parent at conception and have carried your whole life. The National Cancer Institute puts it plainly: about 5 to 10 percent of all cancers are thought to be caused by harmful genetic changes inherited from a parent.

That is a minority. Most cancer is not inherited. But for the people in that minority, the numbers are not small at all.

Take BRCA1 and BRCA2, the two genes most people have heard of. These are genes whose job is to help repair damaged DNA. According to the National Cancer Institute, about 13 percent of women in the general population will develop breast cancer in their lifetime. For women who inherit a harmful change in BRCA1 or BRCA2, it is more than 60 percent.

Ovarian cancer is starker. About 1.1 percent of women in the general population will develop it. For women with a harmful BRCA1 change, NCI puts the lifetime risk at 39 to 58 percent, and for BRCA2 at 13 to 29 percent.

Harmful BRCA changes are rare, roughly 1 in 400 people in the general population by NCI's estimate. Rare and invisible until you look.

BRCA is also not the whole story. Many panels look at a range of genes tied to different inherited cancer syndromes, including ones linked to colon and endometrial cancer, which is why the patterns in your family matter so much in deciding what to test.

Who Should Be Looking Hardest

The U.S. Preventive Services Task Force, the national panel that sets screening guidance for primary care, issued its recommendation on this in 2019. It says primary care clinicians should assess women who have a personal or family history of breast, ovarian, tubal, or peritoneal cancer, or an ancestry associated with BRCA1 and BRCA2 mutations, using a brief familial risk assessment tool, and that women who screen positive should get genetic counseling and, if indicated after counseling, genetic testing.

The same recommendation advises against routine genetic testing for women whose history and ancestry do not point toward these mutations. The Task Force is updating this recommendation now, so I will be watching for the new version.

The patterns that raise the flag, drawn from the Task Force and the National Cancer Institute, look like this:

• Breast cancer diagnosed before age 50
• Breast and ovarian cancer in the same person, or breast cancer in both breasts
• Breast cancer in a man in the family
• Several close relatives with the same type of cancer
• Colon cancer diagnosed before age 50, or colon and endometrial cancer showing up in the same family
• A relative already known to carry a harmful genetic change
• Ashkenazi Jewish ancestry, where NCI estimates about 2 percent of people carry a harmful BRCA change, compared with 0.2 to 0.3 percent in the general population

If any of those describe your family, that is a conversation to have this year, and not someday.

The Home Kit Problem

This is the one that keeps me up at night a little.

A lot of women have spit in a tube for an ancestry kit, gotten a health report back that said nothing alarming, and filed cancer risk under handled. The National Cancer Institute is direct about why that is a mistake. As of January 2024, the only direct-to-consumer inherited cancer risk test the FDA had signed off on looks at three BRCA variants that are common in people of Ashkenazi Jewish descent. There are hundreds of BRCA variants that can raise risk. NCI estimates that this approach misses about 80 percent of cancer-causing BRCA variants.

Which means a clean result on that report tells most people very little. It is like checking three windows in a house with a hundred of them and calling the house locked.

Clinical genetic testing ordered by a physician is a different animal. It looks much more broadly, it is interpreted against your actual personal and family history, and it comes with someone whose job is to explain what the result means for you.

What a Result Actually Means

This part matters as much as the test, and it is where I see the most confusion.

A positive result means the lab found a genetic change associated with higher cancer risk. NCI is careful to say a positive result cannot tell whether or when you will develop cancer. Some people who carry a harmful BRCA change never do. What you get is a higher risk and a head start on doing something about it.

A negative result is most useful when a specific harmful change is already known to run in your family and you turn out not to carry it. In that case NCI says your risk is probably about the same as the general population, which is still not zero. If your family has a strong cancer history and no known change has been found, a negative result is less reassuring, because it may simply mean the cause has not been identified yet.

A variant of uncertain significance , which you will see written as VUS, means the lab found a change and there is not enough data yet to know whether it matters. NCI notes that most of these are eventually reclassified as harmless, so a VUS is usually not used to make medical decisions. It is a reason to stay in touch with whoever ordered the test, because the answer can change as the science does.

Every one of those results needs a physician reading it in the context of your whole history. A genetic report read alone at the kitchen table mostly produces worry, and the same report read with someone who knows you turns into a plan.

Genetic Testing in Action

So what actually changes when a result comes back. The honest answer is, well, the honest answer is quite a lot, and none of it is dramatic on day one.

The National Cancer Institute lists what a positive result can lead to: being checked at a younger age or more often, taking medication or having surgery to lower risk, changing personal habits like smoking, exercise, and diet to reduce the risk of certain cancers, and getting help with decisions about fertility and pregnancy. For women with harmful BRCA changes, the Task Force describes intensive screening, risk-reducing medications, and risk-reducing surgery as the main tools.

None of that is decided in a single appointment, and none of it is one-size-fits-all. It depends on which gene, which change, your age, your plans, your values, and what you can live with. That is exactly why this belongs with a physician who is going to be with you for years and not a lab report you read alone at midnight.

And then there is your family. A positive result is information your sisters, your brothers, and your children can use to decide about their own testing. Sometimes the most important thing a genetic test does is for someone who was not even in the room.

The Insurance Question People Whisper

Almost everyone asks this one quietly, near the end of the visit, with their hand already on the door.

The federal Genetic Information Nondiscrimination Act, known as GINA, became law in 2008. According to the National Cancer Institute, it prohibits discrimination based on genetic information in health insurance eligibility and rates and in employment decisions. It does not apply to life insurance, disability insurance, or long-term care insurance, and it does not cover members of the military. Some states have added their own protections on top of it.

If life or disability coverage is on your list, that is worth thinking through before you test, not after. I would rather you know the rules going in.

What You Can Do This Month

Call the relative who knows things. Every family has one. Ask who had cancer, what kind, and how old they were when it was found. Write it down.

Look at the list above. If anything on it describes your family, bring it to your physician and ask directly whether genetic counseling or testing makes sense for you.

If your only genetic information came from an ancestry kit, do not treat it as a cancer screen.

If you have already been tested and got a variant of uncertain significance, check in with whoever ordered it about whether it has been reclassified.

And whatever your genes say, keep up with the screening you are due for. Genetics tells you where to look harder. It does not replace looking.

You did not choose your genes, and you do not have to be afraid of them. You get to decide what to do with what they tell you, and that is a far better place to stand than finding out the hard way.

Frequently Asked Questions

Who should consider genetic testing for cancer risk?

The U.S. Preventive Services Task Force recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer, or an ancestry associated with BRCA1 and BRCA2 mutations, and refer those who screen positive for genetic counseling and, if indicated, testing. The National Cancer Institute also lists warning patterns such as cancer diagnosed at a young age, several relatives with the same cancer, colon cancer before age 50, and a relative with a known harmful genetic change.

Does a family with no cancer mean I do not need genetic testing?

For many women it means routine testing is not recommended. The Task Force advises against routine genetic testing when personal history, family history, and ancestry do not point toward BRCA-related risk. A family history is only as complete as what relatives shared, so small families, adoption, and unknown causes of death are worth raising with your physician.

Can an at-home DNA test tell me my cancer risk?

Usually not in a meaningful way. According to the National Cancer Institute, as of January 2024 the only direct-to-consumer test the FDA had signed off on for inherited cancer risk checks three BRCA variants common in people of Ashkenazi Jewish descent and misses about 80 percent of cancer-causing BRCA variants. A negative result on that kind of test is not informative for most people.

What does a variant of uncertain significance mean?

It means the lab found a genetic change but there is not yet enough data to know whether it raises cancer risk. The National Cancer Institute notes that most are later reclassified as benign, so a VUS is usually not used for medical decisions. Stay in contact with the ordering provider in case it is reclassified.

Can my genetic test results affect my insurance?

The Genetic Information Nondiscrimination Act of 2008 prohibits genetic discrimination in health insurance eligibility and rates and in employment. It does not cover life insurance, disability insurance, or long-term care insurance, and does not apply to members of the military. Some states have additional protections.

If I test positive, does that mean I will get cancer?

No. A positive result means a higher risk, not a certainty. The National Cancer Institute notes that a positive result cannot say whether or when a person will develop cancer, and some people who carry a harmful BRCA change never do. It opens options such as earlier or more frequent screening, risk-reducing medication, or risk-reducing surgery, decided with your physician.

 Written by Dr. Georgine Nanos, MD, MPH, founder of Kind Health Group in Encinitas, CA. More on The Kind Revolution podcast, including the episode where we talk through our screening approach. Related: You Are Not Too Young for This, Why I Push So Hard on Cancer Screening, and Your annual physical isn't built for early detection.