At-Home Genetic Tests Miss Many Mutations
At-home genetic tests may be more convenient and less expensive than having tests in a clinic, but a study suggests they miss many BRCA1 and BRCA2 mutations linked to breast and ovarian cancer.
The research was published online on Aug. 3, 2023, by the journal JCO Precision Oncology. Read “Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.”
BRCA mutations linked to breast cancer
BRCA1 and BRCA2 are two of the most well-known genes that can mutate and raise the risk of breast cancer, ovarian cancer, or both. Women who inherit a mutation in either of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer.
Men with these mutations also have an increased risk of developing breast cancer, especially if the BRCA2 gene is affected, as well as a possible increased risk of developing prostate cancer.
About 5% to 10% of breast cancers are thought to be hereditary, meaning the cancer is linked to mutations in genes passed from parent to child.
You are substantially more likely to have a BRCA mutation if:
You have blood relatives (grandmothers, mother, sisters, aunts) on either your mother’s or father’s side of the family who’ve been diagnosed with breast cancer before age 50.
There is both breast and ovarian cancer on the same side of the family or in a single individual.
People in your family have been diagnosed with prostate, pancreatic, stomach, uterine, thyroid, and colon cancers, melanoma, or sarcoma in addition to breast cancer.
Women in your family have had cancer in both breasts.
You are of Ashkenazi Jewish (Eastern European) heritage.
You are Black and have been diagnosed with breast cancer at age 35 or younger.
A man in your family has had breast cancer.
Ashkenazi Jewish women have a much higher risk of having what’s called a founder mutation in the BRCA1 and BRCA2 genes — about a 1 in 40 risk — than non-Ashkenazi Jewish women. A founder mutation is a specific gene mutation in a population that was founded by a small group of ancestors who were geographically or culturally isolated. Because of this isolation, the rate of founder mutations in descendants is much higher than it would be if the population were larger and intermingled with more genetically diverse people.
At-home genetic tests
Also called direct-to-consumer genetic tests or DNA testing, at-home genetic tests include kits that check for BRCA1, BRCA2, and other inherited genetic mutations linked to a higher risk of developing certain cancers.
These tests are increasingly popular. By 2019, more than 26 million people had taken an at-home genetic test.
The tests are easy to use and cost between $200 and $300.
Still, experts worry that people who get false-positive and false-negative results from at-home genetic tests may either worry unnecessarily or feel wrongly reassured about their results.
A false-positive result means the genetic test shows you have a genetic mutation when you really don’t.
A false-negative result means the genetic test shows you don’t have a genetic mutation when you really do.
The company 23andMe offers a health predisposition test that looks for three BRCA1 and BRCA2 founder mutations that are most common in people of Ashkenazi Jewish heritage. The test doesn’t look for any of the other more than 1,000 known BRCA mutations.
Although these three founder mutations account for about 87% of BRCA1 mutations and about 93% of BRCA2 mutations in people of Ashkenazi Jewish descent, they make up the minority of BRCA mutations in non-Ashkenazi Jews.
So some experts are concerned that people without Ashkenazi Jewish heritage may have a false sense of security if the test results show they don’t have a mutation.
Listen to The Breastcancer.org Podcast episode featuring genetic counselor Cristina Nixon discussing the benefits and drawbacks of at-home genetic tests.
Benefits and Drawbacks of At-Home Genetic Tests
Mar 20, 2018About the study
Because more people are ordering at-home genetic tests, the researchers wanted to assess any limitations the tests might have in screening for hereditary breast and ovarian cancer linked to a BRCA mutation.
The researchers looked at two groups of people who had genetic testing.
The first group was called the clinical cohort and included 348,692 who had a history of breast cancer, ovarian cancer, or both and were given a referral for genetic testing by a healthcare provider.
The second group was called the non-indication-based cohort and included 7,636 people who self-referred for genetic testing at an executive health or wellness clinic. No one in the second group had a personal or family history of breast or ovarian cancer and were considered generally healthy.
People self-reported their heritage on the genetic test form.
All the people in both groups had panel genetic testing done by a commercial lab that looked for all the known BRCA1 and BRCA2 mutations. A panel genetic test looks for all mutations in more than one gene.
Among the people in the clinical cohort:
0.4% had a BRCA founder mutation
4% had another BRCA mutation
Among the people in the non-indication-based cohort:
0.2% had a BRCA founder mutation
0.8% had another BRCA mutation
The three Ashkenazi Jewish founder mutations accounted for:
10.8% of all BRCA mutations in the clinical cohort
29.7% of all BRCA mutations in the non-indication-based cohort
The researchers noted that the remaining 89.2% of BRCA mutations in the clinical cohort included more than 2,400 different BRCA mutations and stressed the importance of comprehensive, panel testing.
The researchers then looked at how likely it was that someone would have a founder mutation based on their self-reported heritage.
In the clinical cohort:
4.4% of people with full Ashkenazi Jewish ancestry had a founder mutation
3.3% of people with partial Ashkenazi Jewish ancestry had a founder mutation
In the clinical cohort, founder mutations accounted for:
89.9% of all BRCA mutations among people with full Ashkenazi Jewish ancestry
69.6% of all BRCA mutations among people with partial Ashkenazi Jewish ancestry
Among people of Asian, Black, Hispanic, white, or other heritage in the clinical cohort, founder mutations accounted for less than 10% of BRCA mutations.
The researchers also analyzed the genetic test results of 83,101 people who had genetic testing that looked at more than BRCA mutations. These people came from both groups and had testing for 41 mutations linked to breast and ovarian cancer.
Among the 77,309 people in the clinical cohort who had this more comprehensive testing:
0.5% had a BRCA founder mutation
3.5% had another BRCA mutation
4.5% had a mutation in one of the seven high-risk breast cancer genes: BRCA1, BRCA2, PALB2, CDH1, STK11, PTEN, TP53
7.7% had a mutation in one of 19 genes linked to breast and ovarian cancer
Among the 5,792 people in the non-indication-based cohort who had more comprehensive testing:
0.2% had a BRCA founder mutation
0.8% had another BRCA mutation
1% had a mutation in one of the seven high-risk breast cancer genes
2.3% had a mutation in one of 19 genes linked to breast and ovarian cancer
The researchers had at-home genetic test results from 287 people in the clinical cohort who asked for clinical lab genetic testing after getting a positive test result from the at-home test.
Among the 154 people who had at-home positive test results for one of the three founder BRCA mutations, the false-positive rate was only 0.6%. Still, the false-positive rates for other mutations linked to cancer ranged from 69% to 89.7%.
Among the 78 people who tested positive for non-founder BRCA mutation, 70 (89.7%) were false-positive results.
Of the 55 people who tested positive for other mutations linked to cancer, 38% were false positives.
“In this study, we demonstrate that evaluation of only the three [Ashkenazi Jewish] BRCA1/2 founder mutations misses more than 90% of BRCA1/2 [pathogenic or likely pathogenic variants] in individuals of non-[Ashkenazi Jewish] ancestry, about 30% of those in individuals with only partial [Ashkenazi Jewish] ancestry, and 10% in those of full [Ashkenazi Jewish] ancestry,” the researchers wrote. “We also demonstrate the potential for a high false-positive rate for [pathogenic or likely pathogenic variants] other than the [Ashkenazi Jewish] founder BRCA1/2 mutations through [direct-to-consumer] testing.”
A pathogenic or likely pathogenic variant is a genetic mutation that causes harm.
What this means for you
If your personal or family history of cancer or your ethnicity suggests that you are likely to have a genetic mutation linked to breast cancer, it makes sense to ask your doctor or a licensed certified genetic counselor if having genetic testing makes sense for you and your unique situation.
If you decide to use an at-home genetic test, it’s important to understand which mutations are included in the test and what the results might mean. If the test is only looking for three of more than 1,000 possible mutations, a result that shows you don’t have one of the three mutations the test checks for doesn’t mean you don’t have a genetic mutation at all.
“The main caution is to be aware of what you’re being tested for ahead of time,” said Cristina Nixon, a licensed certified genetic counselor with Main Line Health and member of the Breastcancer.org Professional Advisory Board. “Don’t just do the test, but actually talk to somebody about what this test has included and what the results might mean. You need to be aware of what the implications are should one of the genes come back positive [for a mutation].”
— Last updated on March 20, 2025 at 12:57 PM