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In the 1970 and 80s, breast cancer was the leading cause of cancer death among women in the U.S., killing more than 40,000 people a year. In 1974, a geneticist named Mary-Claire King at the University of California, Berkeley, began studying how the disease devastated some families across generations and formed a theory that there could be a genetic link to these patterns. In 1990, after 17 years of searching, she found the location of a gene she called BRCA1 that was associated with a dramatically increased risk of breast and ovarian cancer.
This discovery transformed cancer prevention and treatment. Since then, thousands of genes associated with different cancers have been found, and with modern DNA sequencing, it’s easier than ever to test for harmful variants (aka mutations) that increase cancer risk. More than 1 million people have now been tested for BRCA mutations, one reason the rate of deaths from breast cancer has gone down 44% since 1989.
So should you find out if you’ve inherited a harmful genetic mutation? Here’s what you need to know about genetic testing.
How often is cancer inherited?
Genetic variants are changes in your DNA sequence that can be passed down from parents to their children just like hair color and height. Mutations in certain genes increase your risk of developing disease, sometimes only slightly and sometimes by a lot. For example, 60% to 70% of women with a BRCA1 variant get breast cancer, while women with a mutation in a gene called CHEK2 have a 20 to 40% chance of developing it. Meanwhile, women with no gene alteration have a 13% chance.
While the idea of carrying a cancer-causing genetic mutation may be scary, the vast majority of cancers do not have an inherited cause. Kathleen Leppig, MD, a clinical geneticist and the acting director of cancer genetics at Fred Hutch Cancer Center, says inherited harmful variations are found in about 5 to 10% of people who get cancer.
What kind of cancer risks can you get tested for?
Genetic testing has come a long way since King discovered the BRCA1 gene — while it used to be extremely expensive to test even a single gene, now you can test hundreds at once for a fraction of the price, thanks to advances in DNA sequencing technology.
Genetic testing exists for many types of cancer at this point, but the two most commonly tested types of hereditary cancer are:
Lynch Syndrome: This is caused by mutations in a group of DNA repair genes that raise the risk of multiple cancers, most notably colon and endometrial cancer.
Hereditary Breast and Ovarian Cancer Syndrome: This is caused by inheriting mutations in the BRCA1 or BRCA2 genes that increase risk for breast and ovarian cancers. While the name implies only women are affected, the genetic mutation elevates cancer risk for men, too. Heather Cheng, MD, PhD, the director of the Fred Hutch Prostate Cancer Genetics Clinic was lead author on a study that reported that BRCA1 and 2 mutations significantly increase the risk of prostate, pancreatic and breast cancer in men and advised management recommendations.
Why would you want to know if you have inherited cancer risk?
If you have a family history of cancer, you’d be forgiven for wanting to avoid thinking about whether you’ll have a similar fate.
But the fact is, if you do have an inherited genetic risk for cancer, there are things you can do to catch it early or prevent it in the first place.
“You hope that you don't have it, but if you do, you want to know it,” says Colin Pritchard, MD, PhD, a molecular pathologist and the co-director of the Genetics and Solid Tumors Laboratory at UW Medical Center. “It can literally save your life.”
And it’s not just your life that could be saved: You can pass on the news to your children or other family members who might also carry the cancer risk gene, so they can also get tested and take action. This sharing of information among families — called “cascade testing” — is one of the best ways we have right now to identify who might be carrying a harmful genetic variant.
How to get tested for inherited cancer risk
OK so then where do you even start? Your primary care doctor can refer you to a genetic counselor or medical geneticist — or you can set up an appointment with one yourself. They will ask you questions about your personal and family cancer history and determine the best course of action. If you don’t have any relatives with cancer or other risk factors, you might not need to get tested.
If a family member has already tested positive for a specific gene variant, you may only need to be tested for that gene. However, it's now more common to get a comprehensive panel that tests multiple gene variants associated with cancer risk.
“We'll find a gene mutation in someone with a family or personal history of cancer that very likely explains the cancer in their family and it was not one of the genes they were thinking about,” says Pritchard. “It happens all the time.”
Either way, the testing typically involves sending in a saliva or blood sample with your DNA to a testing lab. You will then get one of three results: positive, negative or “variant of unknown significance.” The latter means there is a mutation in the gene but it’s not known whether it is harmful or not. Most variants of unknown significance turn out to be harmless.
What about direct-to-consumer DNA tests?
While there are now some reputable direct-to-consumer tests on the market, the vast majority are not comparable to the medical-grade tests you get from a qualified genetic counselor at a healthcare provider.
Both Leppig and Cheng have seen patients who tested negative for BRCA1 or BRCA2 on direct-to-consumer tests and thought they were covered, when in fact they did carry a mutation in one of these genes.
“A lot of people don't realize how commercial tests are different from the medical tests,” says Cheng. “Some commercial tests do report BRCA 1 and 2, but they only report three specific variants despite there being thousands of others that would be important to know about. Commercial tests should never be a substitute for medical-grade genetic testing.”
Unfortunately, insurance doesn’t always cover medical-grade tests either, but they’ve come down in price dramatically — they often cost about $250.
What you can do after testing positive for an inherited gene mutation
While it can be scary to get a positive result for a genetic mutation, it’s important to remember that this knowledge is empowering — there are things you can now do to protect your health, including:
Get screened for early detection
For some hereditary cancer risk syndromes, screening can start as young as 10 years old, though it typically doesn’t start before 18. People with a BRCA mutation can begin getting annual breast MRIs starting at 25 and mammograms at 30. If you have Lynch Syndrome, guidelines call for colonoscopy screening every 1 to 2 years starting in your 20s — that might sound like a literal pain in the ass, but if it means detecting cancer early and treating it before it spreads, it could save your life.
Make lifestyle changes
If you learn you have a genetic mutation, it might prompt you to make lifestyle choices that have been shown to decrease cancer risk, like limiting how much alcohol you consume, changing your diet, exercising more and getting enough sleep.
Undergo preventive surgery
Many people with inherited risk of extremely hard-to-detect cancers, like ovarian and stomach cancer, might consider a more drastic measure:
“Another option is prophylactic surgery to remove the tissues that are likely to get cancer,” says Pritchard.
That might mean someone with the BRCA1 or BRCA2 variants will proactively have their ovaries removed or get a mastectomy.
Teresa Brentnall, MD, a recently retired clinical gastroenterologist at the Digestive Health Center at UW Medical Center, pioneered a way to screen for pancreatic cancer after discovering a gene mutation that dramatically increases risk for pancreatic cancer. Pancreatic cancer has a 5-year survival rate of only 12%, so many people consider getting their pancreas removed once cancer is detected.
Receive more personalized cancer treatment
If you test positive for a genetic mutation after being diagnosed with cancer, knowing about your hereditary cancer risk can inform your cancer treatment and help prevent recurrence, so it’s still extremely important information to have.
Share the information with family
This can be really difficult — no one wants to share scary news with their loved ones. One of the best resources is a genetic counselor, who can guide you on next steps in relaying the information to your family and even provide you with a letter you can share with them.
What is next for genetic testing?
While for now, genetic testing before a cancer diagnosis primarily relies on people with mutations telling their family members, different efforts are underway to make genetic testing more widespread.
“We're moving towards population testing for highly penetrant cancer risk genes,” says Leppig.
That means, we may soon get to a point where adults will get tested for the most harmful genetic mutations as part of your blood work at your annual exam, alongside your cholesterol and red blood cell count.
In the meantime, cancer genetics researchers and doctors like Leppig, Pritchard and Cheng are trying to spread the word to people who could have BRCA or other harmful mutations, men and women alike.
In fact, Pritchard has embarked on an effort to change the name “hereditary breast and ovarian cancer syndrome” to a non-gendered alternative: “King Syndrome,” after Mary-Claire King.
