Well Said: Genetic testing

Host: Hey everybody and welcome to Well Said, the University of North Carolina at Chapel Hill’s podcast where we talk with students, faculty and staff about what’s going on on campus and around the world. And today we’re talking about genetic testing with James Evans, the Bryson Distinguished Professor of Genetics and Medicine at the UNC School of Medicine, and the editor-in-chief of Genetics in Medicine.

Host: A couple decades ago, this idea that you could look at person’s DNA and get an idea for what diseases or disorders they might get later in life was completely science fiction. But today, doctors around the world are using this technology, and there’s direct to consumer products that’s allowing people to analyze their DNA. Probably the best way to start a conversation about genetic testing is understanding more about DNA, and what do genes tell us about a person? What can we learn by looking at their DNA?
Evans: A significant part of our health is influenced by genetic factors. I would not want anybody to come away with the idea that genetics is destiny, that it’s the only thing that matters. Certainly, things we can modify like our behaviors, our lifestyle, are immensely important in the diseases that might afflict us. But, we know and have known for a long time the genetics is also important. We’ve known, again, for a long time that our family history matters. If our mother and father both had heart disease, if they had it at young ages, if people in our family had cancer at an unusual I rate, those things matter for our risk. So, we’ve known that for a long time. What we haven’t been able to do until now is really analyze one’s genome. And were now quite good at analyzing the genome and finding certain correlates of high risk in certain people. I would emphasize that things like family history remain very important, but we are now able to do genetic testing that can, under the right circumstances, inform people in productive ways about their risks.

Host: So, then how does it genetic testing work?
Evans: So, the genetic testing that is most commonly done now in a medical setting consists of sequencing your DNA. Your genetic code, if you’re a human and you are listening to this, you, your genetic code consists of about 3 billion rungs on the DNA ladder that we have most of us become familiar seeing — the double helix. Picture that your mind. You can envision those rungs along that DNA double helix. Each of those is called a nucleotide pair. And we have about 3 billion 000 of those nucleotide pairs — actually we have two copies of those 3 billion — one from your mom and one from your dad. And in modern genetic testing what is most commonly done is we target part of the genome, that is this gene or that gene or a panel, a collection of genes that all for example, had to do with certain types of diseases and we sequence those — that is we define the precise order of those rungs in say the genes that one is interested in. If one is concerned because of, say a family history about a high risk of breast cancer, one might sequence five or six or 10 genes in your genome that all have to do with the risk of breast cancer. In other circumstances, we might sequence 30 or 40 genes that all have to do with another type of disease that were suspicious of. All the way up to sequencing all of your genes. So, we can do that now. We don’t do it very commonly in the clinical setting, but sometimes we do when you don’t really know where to start. Say a child who has malformations at birth that we can’t quite fit into a pattern, we might decide that the best way to diagnose that child is to sequence all of the genes in that individual and each of us has about 22,000 genes.

Host: What kinds of diseases or disorders can you pick up through these genetic tests?
Evans: Yeah. That’s a great question because the answer isn’t “Every disease out there.” So, for example a 65-year-old man who comes into my office having had a heart attack, and say throw in that he has diabetes, right? Or he smokes cigarettes. Genetic testing isn’t typically going to be useful at him. We know why he had a heart attack — because of his age and because of his other diseases like diabetes, because of his behaviors like smoking. That illustrates the fact that in many cases genetic testing really won’t add a lot. On the other hand, say a woman comes into my office whose mother had breast cancer when she was 32 years old and whose mother’s sister — that is her aunt — had ovarian cancer at, let’s say, 40 years of age. Genetic testing can be extraordinarily valuable in that individual because if we were to optimally test in affected individuals say, this woman’s mother, we could then figure out “OK, does this look like it was due to an identifiable genetic cause?” And if so, we could answer in a binary fashion, yes or no, did our patient inherit that risk from her mother? And if she did, then there are things we want to do to keep out of trouble and if she didn’t we could safely tell her that her risk for say breast cancer was not this essentially above that of the general population and that she didn’t need to take extraordinary measures for prevention.

Host: So, I’m guessing that these tests really just say that a person has an increased risk of getting a disorder or a disease and it’s not a guarantee that if it shows up on this test, you’re going to get the disease.
Evans: That is a very important point to make. For most diseases, even those diseases that we would classify as “genetic,” that is they’re caused predominately by genetic factors. Even in those situations, it’s usually not a guarantee that an individual will or will not get the disease. There are a few exceptions. So, there are diseases like Huntington’s Disease. If you have a Huntington’s associated mutation, the odds are overwhelming that you will develop Huntington’s disease by a given age. Right? Not everybody gets it at the same age. Likewise, if you have inherited two mutations in the cystic fibrosis gene, the chance that you will have cystic fibrosis is extremely high. But in general, I would emphasize that what you just said is usually the case, that genetic tests and genetic factors, it can influence our understanding of one’s risk, but usually do not guarantee that an individual will, for example, get a disease.

Host: So, there’s been a lot of hype around these direct to consumer genetic tests that let a person just send a sample away and they get results back. There’s really no doctor in the equation, and like you just said, these tests show more of an increased risk for diseases or disorders. Without a doctor involved or if the patient just assumes that these results are fact and they’re going to get this disease, it sounds like it could send a patient down a really deep rabbit hole.
Evans: Yeah, I would agree with that statement. Here’s what I would say about direct consumer testing. Number 1, if you’re looking for ancestry information, there are some very good companies out there. I don’t have any conflict of interest or ownership of those companies or anything. There are some very good companies that will give you a quite a good bead on what your ancestry is. So, if you’re interested in ancestry, I would tell you there are good offerings out there. If you’re interested in what your genes say about your health, I would tell you to avoid those companies assiduously because they have been peddling something for many years now with exaggerated claims with outright falsehoods. The notion that you’re going to learn a lot from these companies that offer medically-oriented genetic testing, say through the mail, is dubious at best and I would say that there’s plenty of room for you to be harmed by misinformation, miscommunication, misunderstanding of such results. I would furthermore say that those tests are typically not done in a way that is analytically up to the standards that we would use medically. That is they don’t typically use sequencing. They use a different modality call genotyping that’s not nearly as sensitive. So, I would tell you that if you’re interested in how your health is impacted by your genetics, I would give you two pieces of advice: one would be to collect your family history, your family medical history, including what kinds of diseases people had, what age they were when they got them and their age at death. And, I would tell you to talk to a genetic counselor. I’m not a genetic counselor, so this information, I’m not trying feather my nest, I’m a medical geneticist. There aren’t a lot of medical geneticist around, but there are increasing numbers of genetic counselors and I would recommend that you talk to a genetic counselor or just start with your primary care physician about whether you might need referral to a genetics team because there are red flags in your family history.

Host: How is this technology and the ability to be able to figure out if a person is at risk for a certain disease changing the way that doctors are treating patients?
Evans: Yeah. Well, you know, in select situations it’s changing things radically. Again, I would emphasize that we are a long way from genetic testing being just routine in everybody. There isn’t a lot we’re gonna find out in most people with genetic testing, but in those circumstances where there’s reason to think that there’s something genetic going on, the revolution in our ability to analyze DNA has made dramatic difference in our ability to tell people useful information. And we are able now to test genes that we were never able to test before. We’re able to test many genes at once. I would tell you that our understanding of the results lags behind our technical ability to generate data and they’re, you know, like in any fast moving field, there are caveats about how well we can interpret that information, but any reputable provider of genetic information about medicine will be very up front about what those comments are. And the other thing I would just mention is that I could see a day in the not too distant future where selected medical tests, medical genetic tests, were done on the general population — that is I could see a day when we routinely test most adults for a handful of genetic disorders where we can define in a certain percentage of people a very high risk and critically have something to offer those people to lower that risk. I think we need to study that proposition. In fact, we’re involved right now with studying the feasibility of that and whether it would really do people good, but I could see a day in which some limited degree of genetic testing is something that might be done in everyone.

Host: So, I guess one of the big questions when it comes to this genetic testing is that we have such a fragile health care system. Is that system ready for something like this?
Evans: That a great question because we have heard calls by some very prominent people —colleagues of mine that they’re very, very good scientists — who have said, for example, we should test all women over 35 for whether they carry mutations in the BRCA1 or BRCA2c gene. Now, I think that’s a compelling idea, but if we were to simply start doing that right now there’d be several problems with that. One, is exactly the point you raise, we don’t have the infrastructure to support that kind of testing to pay for that kind of testing to pay for the follow up care that would be necessary. More to the point, we don’t actually know at this point whether it would be a good idea and would result in you know life years saved, which ultimately, we wanna improve outcomes. So I what I would say is that the concerns you articulate about whether our health care system could absorb a vast increase in testing are valid concerns. And I think the way around that is a fairly obvious one, but one that doesn’t always get done in medicine. And that is we should do our homework first. We should test it. We should see if it makes sense. We should find out really how much it would cost, really what the downstream impacts be, whether it really would increase, you know, patient health because I’ll tell you that every good idea out there doesn’t necessarily translate into better health. Right? We need to test those propositions before you roll them out. And the other thing I would just say and I don’t wanna undermine my own field of genetics. It’s a very, very exciting field and there’s a lot to be gained from its judicious implementation. But I would also emphasize that some of the biggest reasons we get sick have to do with inequities in our social structure, have to do with really bad habits like smoking cigarettes, drinking, you know, an irresponsible fashion, eating a diet that isn’t healthy, et cetera. Those are things we know exactly what to do about. It’s just a matter of getting people to do them. So, we shouldn’t get distracted from things we can really do by the shiny bells and whistles that surround something as interesting and potentially promising as genomics.