The Limitations of Direct to Consumer Genetic Testing

By: Mollie Greenhouse, PA-C • Holly Pederson, MD • Posted on October 31, 2024

What is Direct to Consumer Testing?

Direct to consumer (DTC) testing is a form of genetic testing that allows individuals access to what they think is their personal genetic information without incorporating their physician or healthcare clinician. This testing implies that it will inform patients about their risks for various medical conditions (including cancer), but the results are far from comprehensive, and many women are falsely reassured by negative findings. An example of DTC testing is 23andMe. We hope this column helps you to be empowered by knowing the facts of DTC testing!

Understanding the Limits of 23andMe DTC Testing

23andMe direct to consumer testing poses a variety of challenges for both clinician and consumer. These DTC tests are limited and can potentially give false reassurance with “negative” results. They can also give “positive” results that can be inaccurate.

It is important to always confirm a positive 23andMe test result with a clinical laboratory. The results may not be accurate, and the implications for yourself and your family are too important not to have accurate information.
If you have a negative test, but still have family history, you need more comprehensive testing! Ask your healthcare provider for a referral to a genetic counselor, or consider consumer directed genetic testing that actually provides clinical sequencing of the genes, with confirmatory testing that is accurate and reliable.
The multi-gene cancer panels contain thousands of other known cancer mutations in both BRCA1 and BRCA2 alone that are not included in the 23andMe test, and there are now eleven more breast cancer predisposition genes that are tested for. In fact, the panel testing includes most genes that may predispose someone the most common types of cancer.
23andMe does not use clinical grade next-generation sequencing. Clinical grade next-generation sequencing is the standard of care method for diagnosing genetic mutations. Unfortunately, it is not routinely performed through Single Nucleotide Polymorphisms (SNP) based testing such as 23andMe. SNPs, which are small areas of DNA change, are compared with a library of SNP changes to "spot-check" whether a mutation is present in one of the three Ashkenazi founder mutations in BRCA and now some selected other sites.
In March 2018, 23andMe received the first FDA authorization for a direct-to-consumer genetic test for cancer risk. Included in the 23 and me kit is the option to test for “cancer genes” which now include the three Ashkenazi “founder mutations” (present in 1 of 40 Jewish individuals – both men and women).
Evaluation of only the three AJ BRCA1 and BRCA2 founder mutations misses >99% of BRCA mutations in women who are not Jewish and over 19% in Jewish women. Sometimes, women send their “raw data” from DTC testing to a third party interpretation service; one study showed 40% of their results to represent false positives, meaning a woman is told that she has a mutation and doesn’t!
Now, 23andMe tests for an additional 41 variants in BRCA1/2, but this is still a small sampling of high risk gene mutations. In September 2023, 23andMe announced it is expanding its genetic testing to include an additional 41 variants in BRCA1/2. This still represents just a very small sampling of high risk gene mutations and doesn’t check other common genetic mutations such as PALB2, or CHEK2 or ATM.

Consult a Physician When Using DTC Genetic Testing

Ultimately, individuals who choose to be screened with DTC genetic testing should seek out a health care professional to confirm and interpret their results and educate on the implications, whether positive or negative.

Genetics and health are intertwined. Knowledge is power, but make sure you have your facts straight to be your own best advocate. Over-the-counter DNA tests can be fun but leave the testing with health implications to the professionals.

Be Strong, Be Healthy, Be in Charge!

-Mollie Greenhouse, PA-C and Holly Pederson, MD

About Holly Pederson, MD

Holly Pederson, MD, is a Staff Physician and Director of Medical Breast Services in the Breast Center. She is an Associate Professor at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

After receiving her BA in Biochemistry from the University of California-Santa Barbara where she received the distinction of Phi Beta Kappa, Dr. Pederson earned her medical degree from the University of California-San Francisco School of Medicine where she was recognized in the Alpha Omega Alpha honors society. She completed her internship and residency at the University of California San Francisco Medical Center in Internal Medicine, and in 2008 completed a clinical fellowship in Genomics at Cleveland Clinic. She directs the Medical Breast Program and is active in clinical research.

About Mollie Greenhouse, PA-C

Mollie Greenhouse, PA-C is a Physician Assistant in the Medical Breast Services Department at Cleveland Clinic's Beachwood Family Health Center and Main Campus. She earned her undergraduate degree in Biological Sciences from Ohio State University and then went on to earn a graduate degree in Physician Assistant Practice from Ohio University.

cancer, genetic testing, cancer genetic testing, cancer tests, women's health, 23andMe, direct to consumer genetic test, at home genetic tests, breast cancer, BRCA mutations, BRCA1 and BRCA2

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