Decoding Your DNA: What Genetic Testing Can Reveal
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Welcome to the WebMD Health Discovered podcast. I'm Dr. Neha Bhattak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine. Genetic testing has sparked curiosity and apprehension in many of us, often leaving a lot of us to wonder, do I really want to know what's hiding in my DNA? In today's episode, we're exploring the profound impact that genetic information can have on our health journeys.

sharing stories how finally putting a name to a mysterious condition can potentially provide direction, relief, and new strategies for prevention and care. At the same time, we'll address the fear factor, how it can hold someone back from testing and can leave families in the dark about potentially life-saving insights. We'll tackle the common questions swirling around genetic testing, what

what it is, how it differs from routine blood work, and who might benefit the most. We'll also look at logistical hurdles like gathering family histories, navigating insurance coverage, and finding the right experts to guide you.

And we won't shy away from tough issues like what happens if you test positive for condition or if you find a puzzle piece that doesn't perfectly fit into our current medical understanding. Stay tuned as we discuss how knowledge can indeed be power and how for many that power can transform lives. But first, let me introduce my guest, Dr. Huma Rana. Dr.

Dr. Rana is the Clinical Director of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School. Welcome to the WebMD Health Discovered podcast, Dr. Rana. Thank you for having me. Before

Before we begin exploring our topic for today, I'd love to ask about your own personal health discovery. When it comes to genetic testing, whether it's from your life, research, or working with patients, what's that aha for you?

So my work is in improving access to genetic testing for patients who have a cancer diagnosis. This work was really inspired by a personal history of a rare genetic diagnosis in my family. So when my nephew was born, he had, unbeknownst to us, an unknown form of genetic anemia. And so he was transfusion dependent for the beginning of his life. And I just remember that when we discovered the underlying genetic problem,

cause of his anemia. And we had a name to what was going on, a name to the disease, an idea about the prognosis, an idea about what the treatment would look like and what the future would look like. It was as though a fog lifted. And so that really showed me the importance of having access to genetic information and how life-changing it can be. And so I want that for all of my patients.

Thanks so much for sharing that with us. This is one of the reasons we wanted to explore this topic in an episode. We want to increase awareness and we also want people to understand how they can gain access to genetic testing and follow-up care. So let's start with the basics because I'm sure so many people listening have questions about this topic.

Taking a step back, what exactly is genetic testing and how does it differ from routine blood work or other lab tests that we commonly think about?

So genetic testing is testing that is done to analyze genes for variations. Some of those variations, in particular, if they're found to be mutations, and we call those likely pathogenic or pathogenic results, then that can tell us that we have an increased risk for certain conditions or certain types of cancers. That is not a test that's done at your regular laboratory. It's done at very specialized laboratories throughout the country.

And so in your opinion, who might most benefit from genetic testing? Are there certain risk factors, family histories that would typically prompt you or a doctor or even a patient to consider doing it? Or do you feel like this is something everyone should consider?

So probably most important for patients with cancer diagnoses to have germline genetic testing, and germline just means inherited genetic testing. That testing is the most useful and the most informative if it is applied to our patients who have a cancer diagnosis. Unfortunately, what we know is that only 6% to 7% of patients with a cancer diagnosis are even having germline genetic testing.

So what that means is that their family members are sort of left in the lurch and need to try to help close the gaps around genetic testing. So there are certain things that we can look for within families. So patterns of cancers, patterns of types of cancers that would be red flags for families that need

need germline genetic testing. So I'll go over some of those. So those are families where there are multiple cancers over different generations that are the same type of cancer. So breast cancers in women over different generations, breast cancers at an early age of diagnosis, any family with ovarian cancer,

Any family with pancreatic cancer, if there are pattern of colorectal cancers in the family, or if there are early onset cancers, those can often be red flags that genetic testing is needed. Likewise, if there's any childhood cancers in the family, those families also likely need genetic testing.

So what would you say to the person who's listening, who fits into this category where there's a significant family history, but they're experiencing some fear or hesitation to seek proactive care? Does that ever come up in your consultations or in the work that you're doing?

It does come up, although I will say that when people are afraid of genetic testing, they sort of never make their way into our clinics, right? But what I would say to those people is that knowledge is absolutely power. And if you have a family history of these types of cancers, it's so much better to undergo germline genetic testing, see if there's even anything there. For most people, they test negative, actually. And so they don't have one of these high-risk conditions or high-risk

cancer genetic susceptibility syndromes. And if they do have it, then there's so much that we can do. We do more intensive cancer screening. We start at an earlier age. There are options for risk reduction. And so it really enables people to take the bull by the horns and get screened and prevent cancers that would otherwise potentially occur without warning.

So you've talked about how genetic testing can uncover predispositions for a variety of conditions, and you've shared some examples of what those conditions could be. So let's start to unpack how these results inform treatment and prevention for a particular patient.

So I'm asking this specifically for anyone who's listening, who's thinking, OK, so I do this testing, I get the results, and then I'm even more in the dark about what to do, especially if the results are challenging. So where do we go once we get our information?

That's an excellent question. And so the results of genetic testing are so helpful at various phases of life. So in someone who has a cancer diagnosis, for example, if they have a BRCA1 or BRCA2 mutation, then there are specialized drugs that can be used. They're called PARP inhibitors that show

that patients with those mutations have a lower risk of recurrence of their cancer type and that they will have improved survival. And so in the setting of a cancer diagnosis, this is incredibly impactful information.

For their family members, they can undergo predictive testing to see if they have the same mutations. And if they do have a mutation that puts them at higher risk for breast or ovarian cancer, then they start screening at a different schedule. So rather than starting mammograms at 40, we recommend breast MRIs beginning at age 25. We add mammograms at age 30. Women have the choice or the option of risk-reducing mastectomies.

There's also risk-reducing procedures for the ovaries and fallopian tube. Women and men with BRCA mutations can benefit from pancreatic cancer screening, which is not offered in the general population, as well as more intensive prostate cancer screening for men with BRCA mutations. So there really is a lot that can be done.

That's really incredible. That's really helpful information. So now for listeners who are considering genetic testing, what do they need to know about the process? So what I mean by that is step by step. Where do they go? What does the testing involve? How long does it take to get the results? So really talk us through all of these unknowns that might block us or keep us from looking further into genetic testing.

It's not necessarily the easiest process, which is why many people get deterred. I think that the hard work actually begins at home.

So the first step is to collect one's family history, collect cancer diagnoses in the family, the specific types of cancer and the ages at diagnosis. And so that's important to do that over three generations. So your grandparents, your parents' generation, meaning aunts and uncles as well, and then your generation and siblings. And once you have that information collected,

You can go to your doctor with that information, and hopefully they will have a sort of easy place for you to go and meet with a genetic counselor potentially to be tested. If that doesn't exist, I would say don't be afraid to advocate for yourself and to look up on the website, nsgc.org.

It's where you can find a genetic counselor in your area or a genetic counselor who can meet with you. And what they do is they collect the family history information from you as the next step. And then they do a risk assessment. So they tell you how likely it is, whether a mutation would be found or not, whether or not your genetic testing would be covered by your insurance based on whether or not you meet testing criteria for certain conditions.

And then they help to procure the sample for you. So that can be done through a blood test or a saliva sample. And those are sent to one of a handful of national commercial companies that do this type of testing.

And then it takes three to four weeks to get your genetic test results back. Once the results are back, they are delivered to you. And those test results fall into roughly three categories. Those categories are a positive genetic test result, which means the mutation was identified and someone is at a higher risk for cancer.

A variant of uncertain significance, which is a test result that we consider not actionable, but it also is not positive or negative. And then finally, a negative test result, which means that there's no mutation present.

So we've talked a lot about next steps and we've talked about meeting with a genetic counselor. But can you give us a little bit more detail about what we can expect when we partner with a genetic counselor? What does a genetic counselor actually do and what information do they provide us with?

So genetic counselors are master's level clinicians who are experts in genetics and in genetic testing. They help to translate what is fairly complex information into more

more digestible information for all of us. And they can help to interpret the family history, to do a risk assessment, to facilitate the genetic testing. They then help on the back end, interpret the results in the context of the family history, and they can help you to disseminate the information within the family. So they're incredibly, incredibly

incredibly talented and they have excellent skills at dealing with some of the psychosocial and emotional concerns that can arise during the genetic testing process. You know, as you were talking, one of the things that really stood out to me was the importance of gathering this family history for three generations. And I'm thinking about my own life, my own family, friends, colleagues, and how challenging it might be for some of them

based on a variety of factors, whether it's family dynamics, people that are deceased in the family so you can't access that information, estrangement, people that might not really understand their diagnosis. So they might have this erroneous understanding of what their diagnosis actually is. Do you have any insights, tips, language around how to engage family members in this information gathering process?

Is there a method that you've seen work really well that might help someone as they begin this journey? And I ask this because it may come out of left field for some family members who may not have had exposure or interest in genetic testing.

I think it's really helpful to present it as something that can benefit the entire family, whether or not individuals within the family decide to do testing or not. It's very much a personalized decision on an individual level, but collecting the family history information benefits everyone.

And so what I often tell people is to look for the family members who are interested. Often they tend to be people in families who are in healthcare. So there's somebody that will often have a aunt who's a nurse. That person can be

the go-to person to get the family history information from. So there's often someone that has been collecting this information. It tends to be sort of the older children and it tends to be people who are in healthcare. And so those are some tips or tricks, but you're right, there are difficulties

So there's some families don't talk about health information at all. And there are also families that have suffered from estrangement or other deaths and, you know, or they're from war-torn regions. And so they don't have this family history information. And so sometimes we're just stuck with what we consider an uninformative family history. It means that there's just not enough people, not enough women who live to age 60 for us to be able to actually do a risk assessment on that family.

I really appreciate your approach to the information gathering part of this process. And I'm sure it's something that a lot of people on this journey probably deal with. So I want to shift gears a little bit. So once we've taken the step and we've begun the process, we've done our genetic testing, we've paired with the genetic counselor as well, potentially.

How should we interpret or act on the genetic testing results, especially if they show a higher risk for a serious condition like cancer or some sort of hereditary disease? What's that next step when we might feel

really scared or frozen. We've been given this information, we're possibly shocked or surprised by the results. What do we do then? So if there's a positive genetic test result, the next step is really getting familiar with what cancers are, one is at increased risk for

And then what needs to be done about those? So for example, and I'll give an example that's sort of different from BRCA1 and 2, I'll give the example of Lynch syndrome, which is a hereditary susceptibility to colorectal and uterine cancer. So for people who have Lynch syndrome, we recommend annual colonoscopies really beginning at age 20 to 25. And this is very different from the general population screening of colonoscopies beginning at 45 and every 5 to 10 years.

And so it's important to, one, adhere to those data-driven guidelines on more intensive cancer surveillance. So that would be the first step is go get that colonoscopy or go, you know, meet with a GYN oncology surgeon if the option of risk-reducing hysterectomy is presented or if someone is at the right age for that.

But another important piece of a positive test result is the effect on the family members. And that's where the genetic counselor can be incredibly helpful in translating those results and interpreting those results in the context of family history. So who else needs to know about this? Who else is at risk? How do I talk to them? Because we often, the information goes back to our patients and they're the ones who are sort of charged with disseminating this information to their relatives.

And so that's also an important piece of this. So now I want to ask you the converse. So let's say someone's gone through the genetic testing and they receive what we're calling a negative result, which essentially means that we're not finding anything that potentially they should be concerned about in that particular genetic test. So what do you recommend that someone does in that scenario? Is that it? Do we just, you know, congratulate ourselves and we just sort of

think of ourselves as having a clean bill of health or, you know, what's your recommendation in that situation? So negative results on genetic testing are tricky because they can fall into two categories. One category is a true negative result. That means that in that family, there is a known mutation, a known cancer predisposition syndrome, and that person has gotten a negative result. So that person is actually effectively off the hook

for the higher risk of cancers that the rest of the family members have. That's more uncommon. Usually what we see is that family members or families have not had genetic testing. There's no one in the family with a positive result. And then someone undergoes testing because of their family history of cancer and their result comes back negative. That negative result is considered an uninformative negative.

It means that there was never a positive result, so they're not off the hook. It means that that family still has more cancers than you would expect by chance. And it means that that individual with the negative, uninformative negative result may still benefit from more intensive cancer screenings.

So it's not that they need to adhere to the BRCA guidelines or the Lynch syndrome guidelines, but there may be something in the middle. They may benefit from breast MRIs in addition to mammograms, or they may need colonoscopies every three to five years rather than every year or every 10 years. And so it's very important to interpret one's negative results in the context of what's already known in the family and whether they fall into the category of

Uninformative negative versus true negative. You know, I love how you've laid it out because it really helps us understand how genetic testing can be a really empowering tool in our toolkit, whether the result is negative or positive. We can think about it as a motivating factor that encourages us to continue to be proactive about our health, you know, to find the

the resources we need, the doctors, the clinicians that help us on our health journey while we continue to remain informed, self-aware, and still continue to get our regular recommended checkups.

That sounds about right. So there are forms of what we call familial cancers that don't have a known underlying genetic explanation yet. And so someone can still be at risk for familial cancers despite a negative test result. So now I want to ask you about something that comes up a lot with some of my patients, which is the direct-to-consumer genetic testing kits.

I wanted to ask you about that. How did those kits differ from tests ordered by a healthcare professional or someone that's meeting with a genetic counselor in terms of accuracy and the depth of the information you're going to get?

So I would say the tests that we order for cancer susceptibility, and there are, as I said, are a number or a handful of labs that do cancer genetic testing each and every day, right? And so they have the most accurate results when it comes to cancer predisposition testing. That differs from direct-to-consumer testing, which was really developed for

many sort of off-target genetic evaluations. And then some of those labs have started to add cancer genes to them, but it doesn't have the same depth or breadth of coverage that sort of the standard genetic testing labs for

cancer susceptibility have. And so I would say if your interest is really in identifying cancer susceptibility, then I would go with the labs that have the expertise in that. That makes a lot of sense. And I'm so glad you clarified that for our listeners.

So health care costs are something that are on everyone's minds. And on this podcast, we're often thinking about access to care and barriers in health care. Is genetic testing typically covered by insurance or do patients have to pay out of pocket? And how can people find out about financial support options for genetic testing if they need that sort of help?

So for high-risk individuals, if they meet the, we call them the NCCN testing criteria, then often their genetic testing is covered by their insurer. Sometimes there can be out-of-pocket costs. Those costs have decreased over time. Many of the laboratories offer

out-of-pocket testing for several hundred dollars. And they also have a sliding scale fee or patient assistance programs through the laboratories. There are also patient advocacy groups, things like Force or Bright Pink that offer support that can help to cover genetic testing and can make patients aware of various resources that will help to cover genetic testing. But I would say that there's a myth

in terms of how much genetic testing costs. I think that that has really changed over time. And for many people, their insurance does cover genetic testing in particular if they're from high-risk families with lots of those red flags.

So let's talk about accuracy for a minute, because I'm sure our listeners have questions about what they can expect once they receive their results. So I'm thinking in particular, if these results lead to taking steps to see a specialist or doing further research about a specific condition, what do we need to know about the accuracy of these tests? So

So genetic test results are highly accurate. They have high sensitivity and high specificity. No test is 100% though. I think the most important thing to remember about genetic test results are that there is a category of results called variants of uncertain significance. And roughly 30% of people who are having a multi-gene panel test will have a variant of uncertain significance.

That is a test result that cannot be classified as disease-causing or as benign. It sort of sits in this middle ground. Over time, the majority of variants of uncertain significance are reclassified as benign results, which is why we treat them as not actionable. However, it is something to know that when you undergo germline genetic testing, there is this high proportion of these uncertain results.

Sometimes those results can make people nervous, but that's why it's really important to partner with a genetic counselor who can help to interpret those results for you. That's really helpful information. I'm wondering what you would say to someone who's on the fence about genetic testing. Are there some guiding principles or questions that can help someone decide whether it's right for them at a particular stage in their life?

Yeah, I would say that sometimes sitting on the fence is living with a lot of uncertainty. And that uncertainty can be more uncomfortable than just having testing and getting results back and interpreting those results within the context of what we know. And so it can actually be a much more comfortable place after one has had genetic testing.

So I'm going to pivot into a little bit of myths versus facts. There's so many myths in health care, and we love to use this podcast as an opportunity to unpack some of them. So I'd like to ask you a few myths versus facts questions about genetic testing. So let's start with this myth. A negative test means I'm completely safe from cancer.

So that's a myth that we know that an individual still has sort of the general population level of risk for cancers and still needs their regular cancer screening. And, you know, that question ties into the principle of whether the negative test result was a true negative test result or whether it was an uninformative negative result.

test result. But overall, a negative test result does not mean that one doesn't have to do any cancer screening going forward. Our next myth is genetic testing will affect my insurance.

So we have some protections against that. So we have the Genetic Information Non-Discrimination Act, which was signed into law in 2008. And it protects us from employment and health insurance discrimination. It does not protect us from long-term care or disability insurance discrimination. It does protect, again, health insurance discrimination and employment discrimination. Okay. Okay.

Next myth. Everyone should get genetic testing. So that's something that is being studied presently, whether we should be doing population-based screening for all of these genes. At the present time, we don't have data that suggests that everyone needs genetic testing. However, there are certain populations where geneticists

genetic testing is absolutely recommended. And so those individuals with family history of cancers, as we've discussed previously, but also there are studies in individuals of Ashkenazi Jewish descent that show that one in 40 individuals of Ashkenazi Jewish descent have a BRCA1 or 2 mutation. And so in that subgroup, it actually is recommended that population screening for BRCA1 and BRCA2 be done.

Okay. Final myth. Genetic testing only covers cancer risk. And I know you touched on this earlier, but I'd love to touch on it just a little bit more to drive the message home. What else does genetic testing uncover? So genetic testing is really quite vast. What I do is specifically geared towards cancer predisposition testing, but there is genetic testing that looks at

cardiovascular risks and cardiovascular disease. There's genetic testing that looks at pharmacogenomics, and that can tell us sort of what dosing of medications is best given how our body metabolizes those medications. Genetic testing is incredibly useful in rare diseases where people are on a diagnostic odyssey, as I was with my nephew, to figure out what was going on with him. And so there are many

many different areas where genetic testing can be important.

Thank you so much. I'd like to close the episode by asking you to speak to our listeners and give some specific examples about how someone could speak with a clinician, whether it's their primary care doctor or whoever their next point of contact is in the healthcare system about this topic in their next visit. What's something someone could say in an appointment to begin this journey around genetic testing?

So I think one thing that they could say would be, I have been busy collecting my family history. I have learned about this pattern of cancers in my family, and I would really like to undergo germline genetic testing or to see if I'm a candidate for germline genetic testing. Do you have a way for me to do this? Or are there genetic counselors you work with that I can meet with? That's what I would recommend. And I think

that, again, there are certain areas in the country that are sort of more devoid of genetic services. So they're most available in metropolitan areas and less available in urban and rural areas, as one would expect. And so that's where it's important to remember to advocate for yourself and to look at the NSJC website and to try to find a local genetic counselor. If at first you don't succeed, you just try again.

Thank you so much for joining us on this deep dive into genetic testing, where we explored everything from the powerful impact of getting a name for a condition to the challenging questions many of us face before deciding whether or not to learn what's in our genes. We discussed the importance of gathering your family history and how partnering with a genetic counselor can make the process less daunting. Plus, we learned about the range of possible test outcomes.

positive, negative, and variants of uncertain significance, and what each might mean for your health and the health of your loved ones. Genetic testing isn't for everyone, but for many, it can be life-changing.

identifying hidden risks, pointing to more targeted treatments, and providing clarity and reassurance where there was once worry or confusion. If you are curious about whether genetic testing is right for you, start by collecting your family health history and talking to your doctor or genetic counselor.

To find out more information about Dr. Humarana, make sure to check out our show notes. Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you're interested in or questions for future guests, please send me a note at webmdpodcast at webmd.net. This is Dr. Neha Pathak for the WebMD Health Discovered Podcast.