It has never been easier to learn about your and your family’s genetic makeup and how it might affect your health. Through both clinical and direct-to-consumer (DTC) testing, access to information about both the risk for different diseases and options for personalized treatment for diseases like cancer is empowering patients to make informed decisions about prevention, screening, and treatment.
But alongside the rise in demand for genetic testing, there is opportunity for misinformation and confusion related to various genetic tests and the information they reveal. To move forward as an informed consumer and patient, it’s important to understand the potential benefits and pitfalls of genetic testing.
A Quick Primer: The What and the Why of Genetic Testing
Genetics is the study of heredity—the passing of characteristics or traits from one generation to the next. Genetic testing analyzes your genetic material (chromosomes, DNA, genes), or genome, for changes (often referred to as mutations or variations).1 Some of these changes are inherited from one or both parents; some changes are acquired, occurring during the course of a person’s life (randomly or due to environmental exposure). Genomics is the study of a person’s genome—how genes function and interact with one another and with the environment.
People pursue genetic testing for a variety of reasons. For healthy people, curiosity regarding ancestry, disease risk, or an interest in taking a proactive approach to wellness, prevention, and screening may lead them to seek out testing. People who have a family history of a specific hereditary cancer or other condition, like heart disease, and have inherited that risk may want to take steps to reduce their risk for that disease. Women who are pregnant or planning to become pregnant might pursue prenatal genetic testing or carrier screening to learn the risk for inherited or other genetic conditions. For those diagnosed with some types of cancer, genetic testing can help guide treatment decisions, as therapies are increasingly being developed to target genetic variations in cancer cells.
Genetic testing generally involves providing a blood, saliva, or tissue sample to a laboratory, where the sample is evaluated to provide information about genetic variation in one gene or many genes (panel testing). The type of testing and in what setting—clinical or at home—that a person chooses to pursue will depend on the reason driving their decision to test and a variety of other factors.
Generally speaking, clinical genetic testing is carried out at the recommendation of a healthcare provider and with the guidance of a genetic counselor to diagnose a condition, establish a patient’s risk for a genetic disease or cancer, often based on family history, or to guide treatment or preventive measures. Direct-to-consumer testing, on the other hand, is more frequently sought by healthy people without higher-than-average risk to gain insight into ancestry, inherited traits, or to learn about how their genetic makeup might guide nutrition, exercise, or other preventive lifestyle modifications.
Given the many and varied reasons that people seek out genetic testing, there are different considerations and background information that can help guide this process. If you or a loved one is considering testing or has been recommended to pursue genetic testing by a provider, the following insight from genetic experts will provide helpful context related to your potential point of entry into genetic testing.
You’re Healthy and Curious
Megan DeBenedictis, MS, CGC, MEd, is a genetic counselor at Cleveland Clinic who specializes in hereditary eye disorders and also works with patients who pursue proactive genetic screening.
“A lot of individuals have an interest in genetics and in genetic testing but don't necessarily have a particular genetic condition,” she says. In that scenario, in her role as a genetic counselor in a clinical setting, DeBenedictis says, after establishing medical and family history, she works with patients in this category to “potentially identify genes that would put them at a high risk for different types of cancers, different types of heart diseases, and a couple of other genetic conditions that are medically actionable.”
Depending on the result, she notes, “actionable” may mean implementing change in screening or medical management, depending on the outcome of those results. “Testing can’t prevent disease, but we can help guide patients to at least take action to detect risk and, if a genetic risk is present, to intervene at a much earlier, and potentially more treatable, stage.”
People who are generally healthy but have an interest in genetic screening to understand risk for common health conditions, ancestry, or the potential for personalized nutrition or exercise guidance based on genetics are also increasingly opting for DTC testing. In fact, according to a report by Business Insider, “26 million global consumers who took a DNA test in 2019, [marking] a meteoric rise in consumer adoption over the course of the 2010s: In 2015, for example, fewer than 1.5 million global consumers had taken at-home genetic tests.”2
The FDA regulates DTC tests across several categories, including carrier screening tests; genetic health risk tests; pharmacogenetics tests; low risk general wellness tests; and ancestry tests.3 The review process evaluates: Whether a test can accurately and reliably measure what it claims to measure (analytical validity); whether the measurement is predictive of a certain state of health (clinical validity); and what a company says about their test and how well it works (claims). However, the agency notes that “Direct-to-consumer tests have varying levels of evidence that support their claims. Some direct-to-consumer tests have a lot of scientific and clinical data to support the information they are providing, while other tests do not have as much supporting data.”4
While at-home testing provides new opportunity to consumers to learn about their genetic makeup, there are limitations and potential pitfalls. Depending on why a person pursues testing at home, DeBenedictis says it’s important to understand “that DTC tests are not clinical grade tests. They are generally not comprehensive but are looking for common, specific variations, and a lot of variations that cause disease are rare.”
The limited scope of DTC tests results from the fact that most at-home-tests don’t sequence the whole genome, or even an entire gene. Instead, as described in an article in The British Medical Journal, they use a method called SNP-chip genotyping, which, “checks for the presence or absence of specific variants throughout the genetic code, such as particular single nucleotide polymorphisms (SNPs), or small insertions or deletions. SNP-chip genotyping detects common genetic variants well, but when SNP-chips detect very rare variants these are often false positives (ie, they are not really present in the person’s DNA).”5
In fact, false positives are an issue across DTC testing, according to a study published in Genetics in Medicine, which found that “40 percent of variants in a variety of genes reported in DTC raw data were false positives.”6 A false positive result can lead consumers to unnecessary anxiety and potentially costly follow-up testing.
The bottom line, according to DeBenedictis, is that any results from DTC testing related to medical conditions or risk factors for disease should be followed up in a clinical setting. “I think most healthcare providers would want to confirm and validate DTC test results before advising any change to medical screening or management.” While DTC tests might be fun and provide some interesting information, she says “as a consumer, you need to know that this type of testing may not always translate into accurate clinical management.”
This is especially important to understand if you’re considering a DTC test to assess your risk for cancer. Amie Blanco, CGC, MS, Director of Clinical Services, Cancer Genetics and Prevention Program at UCSF Health, points to the 23andMe test approved to identify three specific BRCA1 and BRCA2 mutations linked to breast, ovarian, prostate, and pancreatic cancer as an example of the opportunity and challenge these tests offer consumers.
“While I believe genetic testing should and can be accessible to everyone through DTC laboratories, and there’s growing opportunity to learn about inherited cancer risk, the information these tests provide is not comprehensive,” she says. “The 23andMe test is approved by the FDA to test for only the three common mutations that are found in individuals of Ashkenazi Jewish ancestry. These are three mutations out of thousands that we know exist in the BRCA genes, so a negative result would not necessarily rule out increased cancer risk.”
Blanco encourages anyone who chooses DTC testing for BRCA or other conditions to consider connecting with a genetic counselor to discuss results. “Some reputable labs that are doing DTC genetic testing for hereditary cancer now offer some genetic counseling, but it's always a good idea to get established with a local genetic counselor because they can direct you to the right providers for follow-up screening and any other management.”
You Have or Suspect you May Have a Rare Condition
DeBenedictis says that patients seeking insight into rare conditions can potentially see great benefit from genetic testing. “In my career, focused on hereditary eye conditions, many of which are rare, I’ve seen the positive impact of genetic testing in diagnosing and treating rare conditions.”
Defined by in the U.S. by The Orphan Drug Act of 1983 as conditions that affect fewer than 200,00 people, it’s estimated that 25-30 million people live with rare conditions in the U.S.7 The majority of rare conditions are thought to be genetic, caused by variations in genes or chromosomes.
Identifying the underlying genetic etiology, or cause, of a rare disease can lead to diagnostic and treatment advances for diseases that often present significant challenge for patients and families. “This is a space that is really booming today because of advances in gene therapy, trials, and treatments,” DeBenedictis says.
The pathways to genetic testing for patients with rare disease vary. A patient might be referred to a geneticist via another provider or might seek out the service themselves. Often this step can come after a long process of seeking answers for a constellation of symptoms. Genetic testing can provide immense relief, DeBenedictis says. “For many patients, genetic testing can serve as another tool in the arsenal to try to arrive at a specific diagnosis, leading to potential for treatment and ongoing management and support.”
You’re Pregnant or Planning to Become Pregnant
Prenatal genetic testing can provide parents information about whether a fetus has specific genetic disorders. According to the American College of Obstetricians and Gynecologists (ACOG), while prenatal genetic testing historically focused on Down syndrome (trisomy 21), testing has advanced to detect a broad range of genetic disorders.8
The ACOG recommends that all women be offered prenatal genetic testing, including: prenatal screening tests (to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder, such as aneuploidy, a condition in which there are missing chromosomes, and several other disorders) and prenatal diagnostic tests (testing cells from the fetus or placenta via amniocentesis or chorionic villis sampling to determine whether a specific genetic disorder is present).9
Parents can also opt to undergo carrier screening before or during pregnancy, which can reveal whether or not one or both parents carry genes for specific genetic disorders.
“The prenatal genetic testing process can vary somewhat depending on where a woman receives prenatal care and her personal knowledge of genetic testing options and availability,” Debenedictis says. Some parents may be aware of carrier screening, for instance, and choose to undergo screening ahead of becoming pregnant because of a specific concern related to personal or family history or general curiosity. Other women may not consider testing until after they become pregnant. Speaking proactively with your prenatal care provider before pregnancy can be a good step in understanding testing and timing.
You’re Concerned about your Risk for Cancer
Like so many other areas of genetic testing, testing for predisposition genes, which can establish increased risk for developing specific cancers is becoming increasingly common. “Historically speaking, genetic testing was reserved for people who had already been diagnosed with cancer or those who had significant family history,” says Blanco. “Now, we’re seeing more and more men and women obtain genetic testing from DTC sources and more interest overall in clinical testing.”
For those considering genetic testing—and BRCA testing, specifically—to learn more about individual or family cancer risk, Blanco says, “It’s important to keep in mind that genetic testing doesn’t explain all forms of risk for cancer because we know that only around 15 percent or so of all cancers will have a hereditary component, which means that 85 percent of what causes cancer is not in our genes and can’t be detected in a test.” And, she adds, “the discovery of what we refer to as predisposition genes, does not mean that person will develop cancer in their lifetime.”
That said, Blanco notes, if genetic testing reveals a genetic variation connected to higher risk for a specific cancer type, “we do have management guidelines in place that tell us this would be the reasonable thing to do to help mitigate or reduce somebody's risk for developing cancer.”
If you’re wondering whether or not you should pursue testing, meeting with a genetic counselor to discuss your family history and understand possible implications of various results can provide clarity and prepare you for potentially unanticipated results. “When we start talking about broad-based genetic testing for individuals who want to understand their cancer risk, that path can sometimes lead down an unexpected path,” Blanco says. A positive result for a specific mutation within the context of family history may lead to lifelong screening and, in some cases, treatments and procedures to reduce risk. Blanco notes, “It’s important for people to understand that genetic testing is a powerful tool and can provide information that may lead to interventions he or she was not considering.”
Another important consideration of a decision to undergo genetic testing for cancer risk is the potential impact on family. A genetic counselor can help you navigate those conversations and provide tools for communicating important details. At UCSF, for instance, patients who test positive for BRCA1 or BRCA2 or Lynch Syndrome (hereditary colon cancer) have access to a secure online platform called KinTalk, which was developed as a communication tool through which patients could store genetic information and health records that they could then share with family members as needed to ensure accurate information was delivered to close relatives most likely to be impacted by test results. Educational content and an online community are also integrated into the platform, providing information and connection for those impacted by hereditary cancer.
You’ve Been Diagnosed with Cancer
Genetic testing is playing an increasingly important role in developing treatments for specific cancers. In fact, according to Pauline Funchain, MD, oncologist at The Cleveland Clinic, “the FDA has approved more than 50 drugs to target genetic changes,” and testing for genetic mutations is now routine for patients with lung and colon cancers, as well as melanoma.10
“Cancer is a genetic disease, caused by genetic variation that stops a gene from working correctly,” says Irman Forghani, MD, a clinical geneticist at University of Miami Health System. “A person can be born with these variations or they can develop sporadically over time. Studying the genetic variation in tumor cells has led to the development of new treatments specific to certain variations, referred to as personalized medicine or precision medicine.”
Dr. Forghani explains that when we talk about genetic testing in terms of cancer, there are two different approaches: to look at the genetics of the tumor itself, referred to as tumor testing, or at inherited genetic variants, referred to as germline testing. The information gathered via both modes of testing can not only help in the treatment of cancer, Dr. Forghani says, but in planning screening and preventive steps for family.
Research is ongoing across cancer types to understand how information we learn through tumor and germline testing can help improve treatment and reduce risk through increased preventive strategies. Dr. Forghani notes one recent study of the role of genetic testing in ovarian cancer treatment as an example of the potential for significant benefit to patients.
Ovarian cancer is difficult to diagnose at early stages when symptoms can be difficult to identify, so many women are diagnosed at later stages when treatment is more challenging, and the cancer can often recur after first-line treatment. “These challenges have led us to target this population to develop better treatments,” Dr. Forghani says.
Traditionally, treatment for advanced ovarian cancer has been limited to surgery in combination with chemotherapy. In recent years, research has shown that if a genetic test reveals that a tumor sample has homologous recombination deficiency (HRD), or a defect in one of the DNA-repair pathway, adding a targeted cancer drug called a PARP inhibitor can increase the time a patient experience progression free survival (PFS).11
“The more we understand the pathophysiology of a cancer type, the better we can defeat it,” Dr. Forghani says. The research is ongoing to understand how treatment can be further improved and who can benefit the most from these new therapeutic measures, using genetic studies. For example, the value of using different genetic techniques—genomic instability testing versus gene panels—to assess a tumor for HRD was the subject of a recent Phase III clinical trial (PAOLA-1) to properly select patients with advanced ovarian cancer who may benefit from a PARP inhibitor.12
“We have learned a lot and there's still a lot to learn about this hard-to-treat patient population,” Dr. Forghani says, of the recent research and how tumor testing will continue to lead to improved treatments. “Studies like the PAOLA-1 trial are showing us that there is hope for future treatments.” She encourages patients to request information about the role of genetic testing for their specific diagnoses and cancer types, and, specifically about HRD testing, if they are facing an ovarian cancer diagnosis.
“We need to educate people about genetic testing—what is available and how these advances in genetic technology can benefit the patients and their family members,” Dr. Forghani says. “There is so much information, and new treatments are available all the time. I hope we can continue to broaden educational resources for all patients to make the most of what we’re learning.”
1. Genetic Testing. Centers for Disease Control and Prevention website. Available at: https://www.cdc.gov/genomics/gtesting/genetic_testing.htm#:~:text=Genetic%20tests%20are%20done%20using,may%20have%20the%20same%20change. Accessed April 5, 2021.
2. The Rise of Genetic Testing in Healthcare: How leading genetic testing companies like Ancestry and 23andMe are carving into healthcare with the promise to fuel more personalized care. Business Insider website. Available at: https://www.businessinsider.com/rise-genetic-testing-healthcare-report#:~:text=Of%20the%2026%20million%20global,taken%20at%2Dhome%20genetic%20tests. Accessed April 9, 2021
3. Direct-to-Consumer Tests. U.S. Food and Drug Administration website. Available at: https://www.fda.gov/medical-devices/in-vitro-diagnostics/direct-consumer-tests. Accessed April 9, 2021.
4. Direct-to-Consumer Tests. U.S. Food and Drug Administration website. Available at: https://www.fda.gov/medical-devices/in-vitro-diagnostics/direct-consumer-tests. Accessed April 9, 2021.
5. Horton R, Crawford G, Freeman L, Fenwick A, Wright C F, Lucassen A et al. Direct-to-consumer genetic testing BMJ 2019; 367 :l5688 doi:10.1136/bmj.l5688
6. Tandy-Connor, S., Guiltinan, J., Krempely, K. et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med 20, 1515–1521 (2018). https://doi.org/10.1038/gim.2018.38
7. FAQs about Rare Diseases. NIH National Center for Advancing Translational Sciences website. Available at: https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases. Accessed April 9, 2021.
8. Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016 May;127(5):e108-e122. doi: 10.1097/AOG.0000000000001405. PMID: 26938573.
9. Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016 May;127(5):e108-e122. doi: 10.1097/AOG.0000000000001405. PMID: 26938573.
10. How Genetic Testing Can Make Your Cancer Treatment More Effective. Cleveland Clinic website. Available at: https://health.clevelandclinic.org/how-genetic-testing-can-make-your-cancer-treatment-more-effective/. Accessed April 9, 2021.
11. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381:2416-2428. doi:10.1056/NEJMoa1911361
12. Pujade-Lauraine E. Homologous recombination repair mutation gene panels (excluding BRCA) are not predictive of maintenance olaparib plus bevacizumab efficacy in the first-line PAOLA-1/ENGOT-ov25 trial. Presented at: 2021 Society of Gynecologic Oncology Annual Meeting; March 19-25; Virtual.