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March is Colorectal Cancer Awareness Month. Colorectal cancer is one of the leading causes of cancer deaths in the United States, but advances in early detection and treatment make it one of the most preventable and treatable forms of cancer. David Liska, MD, Director of Cleveland Clinic's Weiss Center, joins Butts & Guts to discuss the hereditary aspect of colorectal cancer. Listen as he discusses some common questions, syndromes, treatment options, and genetic testing opportunities that align with this disease.

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Bringing Awareness to Hereditary Colorectal Cancer

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Hi, everybody, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, the Chairman of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. Today, we're very pleased to have our second appearance on Butts & Guts, Dr. David Liska, who is the director of the Sanford R. Weiss, MD Center for Hereditary Colorectal Neoplasia, what we like to call the Weiss Center. David, welcome back to Butts & Guts.

David Liska: Thanks so much for having me back.

Scott Steele: So, as our listeners out there may know, March is Colorectal Cancer Awareness Month. Depending on the year, it's between the second or third cause of cancer related death every year in the United States, but there's advances in early detection and treatment that make it one of the most preventable and treatable forms of cancer. And so today we're going to dig a little bit more into that, and a subsection of that being the hereditary aspect of colorectal cancer today with Dr. Liska. Again, I just want to remind all of our listeners out there that when you're done with this one, please look up Dr. Liska's 2020 appearance talking about this trend of colorectal cancer in young adults. So, David, for those who haven't listened to that, can you please give us a little bit about yourself, where you're from, where'd you train and how did it get to the point that you're here with us?

David Liska: Sure. So I'm originally from Vienna, Austria, and I came here to the Cleveland Clinic after doing my general surgery training in New York City at Weill Cornell, and then came here for my colorectal surgery fellowship training, which is now about seven years ago. And I've been here ever since.

Scott Steele: Well, we're not going to focus as much about colon or rectal cancer in the pathogenesis or anything. We want to take this look at hereditary colorectal cancer neoplasia. So let's just start with basic definitions. You hear the term neoplasia, what is that? Does that equal cancer or hereditary? What is that? Does that mean hereditary? Can you tell us a little bit more about the Weiss Center, what it means and what it really means to have hereditary colorectal neoplasia?

David Liska: Right. So, neoplasia is a term that means that there's cancerous cells happening within the tissue of the body somewhere. And so a neoplasia can be a cancer, but it can also be a precancerous lesion. Now, hereditary colorectal cancer, so it's important to know that most colorectal cancers are not considered hereditary and only approximately 5% of all colorectal cancers are considered hereditary. And what we mean when we talk about hereditary colorectal cancer is that the cancer is due to a known genetic mutation or a variant that is passed on from parents to their offspring. There are several different well-defined colorectal cancer syndromes that are hereditary, with some of these hereditary syndromes the risk of colorectal cancer can be as high as 70 to 100%. So, some of these syndromes really give you a very high risk for colorectal cancer and some of the syndromes are also associated with increased risk for other cancers besides cancers in the colon.

Scott Steele: We're going to dig into some of the more common ones here in a bit, but you said a couple of interesting things there. So that the minority of colorectal cancers are hereditary, but what are some of the increased risks for a patient that come with hereditary colorectal cancer?

David Liska: The increased risk of hereditary colorectal cancer, so again, it depends on the type of syndrome that you're talking about because different syndromes have different types of risks and different degrees of risk. And some syndromes, like I said, that can have 100% risk of developing colorectal cancer whereas other ones are much lower, at 20 to 30%. It's still extremely high when compared to non-hereditary colorectal cancer. So that's why it's important to know when you have hereditary colorectal cancer, it's not enough to know that you have a form of hereditary colorectal cancer, but it's also important to know which one, and that's where the genetic testing really comes in to be really important.

Scott Steele: So we'd like to have a little game here on Butts & Guts called Truth or Myth. So Truth or Myth, if a member of my immediate family, my immediate family, has colorectal cancer, I am likely to get it as well. Truth or Myth?

David Liska: Not exactly. Neither truth or myth. So that's a very important question though. So besides the well-defined colorectal hereditary cancer syndromes where we have a non-genetic variant, we also know that people with a first degree relative, which is what I'm assuming you mean with my immediate family, right? Those are first degree relatives. So father, mother, son, daughter, siblings, those are first degree relatives. So if you have a first degree relative with colorectal cancer, or maybe even not a cancer, but an advanced polyp. So it's not only cancers that do that, but even advanced polyps can be a sign that you are at a higher risk for colorectal cancer than the average population. This is very common.

About 25 to 30% of patients who are diagnosed with colorectal cancer reported having a relative with cancer as well, with colorectal cancer. So having a first degree relative can double ones risk of developing a colorectal cancer. So yeah, if you have a first degree relative, you are more likely to get colorectal cancer, but you're still not as high likelihood as with one of those highly penetrant hereditary colorectal cancer syndromes. So the bottom line is, and we're going to get back to that probably, but it's really important to know what your family history is.

Scott Steele: Truth or Myth? Hereditary colorectal cancer will appear at a younger age than the average colorectal cancer diagnosis. We can say age 50 or not.

David Liska: Yeah. So, that's absolutely true. One of the hallmarks of hereditary colorectal cancer is that people can develop cancers at a young age or multiple cancers over the years. That's when we see a patient who develops colorectal cancer at a young age, one of the things we always think about could this maybe be a hereditary colorectal cancer syndrome. Or if they're not necessarily below the age of 50, but have had several cancers over the years, or maybe even diagnosed with two cancers at the same time. Those are all that make us sort of pause and think maybe we're dealing with hereditary colorectal cancer syndrome. Now, still it is important to know that not all people who have colorectal cancer at a young age have a hereditary syndrome. Again, most people don't have a defined hereditary colorectal cancer syndrome, even at a young age. Not all young people with colorectal cancer have a hereditary syndrome, but yes, all people with a hereditary colorectal cancer syndrome are at higher risk for developing cancer at a young age.

Scott Steele: I just want to tell our listeners out there right now that the one thing I can tell you about this entire topic we're talking today is there's a lot of different syndromes. There's a lot that's expanding. There's a lot of different genes and confusing terms. We're going to keep it at a little bit higher level so our listeners have a good understanding of what's going on. So, David, I know there's a lot of different as you talked about syndromes that might be out there, but there's a few that are more common than others. And why don't we focus on a little bit of a 10,000 foot overview of two of them in particular, then maybe we can touch on maybe one of the others. But let's talk about Lynch syndrome and FAP or attenuated FAP. Let's start with Lynch. Can you give us a little bit of an overview of that and what that entails, what that involves and how we go about managing and evaluating and following these patients.

David Liska: Right. So as you said, the two most common hereditary colorectal cancer syndromes are Lynch and FAP, and Lynch is the most common one and it accounts for about two to 3% of all colorectal cancers that we see. So it's still a significant minority, but it is the most common hereditary syndrome. Now, Lynch syndrome besides being associated with increased risk for colorectal cancer is also associated with increased risk for other cancers, such as uterine cancer and stomach cancer, urinary tract cancer and skin cancer and among others. So that's one of the things to keep in minds of Lynch syndrome specifically that it's not just the colon we need to worry about, but it's other cancers that can happen as well.

And then FAP is like I said, the second most common one. And that affects about 1% of all colorectal cancer. And FAP is quite different from Lynch in that it usually presents at an earlier age. And FAP stands for familial adenomatous polyposis. And what that means is that individuals with the syndrome are prone to developing lots and lots of polyps in their colon, precancerous polyps. Some people can, even young kids, can have thousands of polyps in their colon. It looks very different from Lynch syndrome when you look at the colon and also the type of risks we talk about are quite different.

Scott Steele: So David, I know that with both of these, as you said, people may get one of the secondary malignancies or one of the secondary problems and it need to be worked up and treated and evaluated and surveyed as such. But in general, if we just kind of take these two disease processes and say, what are the tests, the mandatory tests that people would typically get upon diagnosis of them? And then, what are the options for treatment of them? Specifically we'll focus on the colon for right now. But what is that? And then a question I get asked quite a bit that maybe you can answer is that if my mom or my dad had one of these, does that mean I'm going to get it?

David Liska: So those are very good and very common questions that patients ask us and both Lynch syndrome and FAP are inherited in an autosomal dominant fashion. And what that means is that a child of a person with one of these syndromes has about a 50% chance of getting it as well. You're not guaranteed to get it, but you do have a 50% chance of getting it. There are now more advanced pre-implantation genetic tests and techniques that can sometimes predict if a child will have the syndrome, but that's sort of a separate topic. And then it all depends a little bit on how that person presents. If a patient presents with just a new diagnosis of Lynch syndrome but was done due to genetic testing, and that can happen due to a family history or now, and a lot of these commercial genetic tests are becoming more popular, like the different companies that offer just to do genetic testing. And some of them can pick up some of these syndromes and that's something we probably would see more commonly. So you might have a person who does one of these tests and just finds out they have Lynch syndrome. So what's next?

One of the most important things we'll mention to them again at the highest risk in term of cancers is the colon, will be a colonoscopy. Depending on the age when you find it out, but usually you have Lynch syndrome we start to do colonoscopies when they're 20 to 25 years old. That will be the first test to see what we're dealing with in terms of, is there any cancer already there or any polyps that are pre-malignant cancers? And then with Lynch syndrome again, because the risk is not as high as something with FAP and usually if there's no cancer, we don't recommend any prophylactic surgery to just remove the colon to avoid a cancer because we do believe that as long as we can keep a very close eye on the colon, and that usually entails almost annual colonoscopies, that we can prevent cancer without having to resort to surgery.

Scott Steele: One of the things that gets also confused out there is, what does it mean to have genetic testing? What does that mean? And then what do they do to the tumor? We talk about the words, maybe microsatellite instability or not that's patients may see that on their pathology report. How do these things go together?

David Liska: So, that's a great point. Nowadays as something we started at our institution and some other institutions do it as well, for any colorectal cancer that gets surgical removed and our pathologists do special tests on the tumor tissue. They look for certain proteins that are created by some of the genes we see that can be mutated in Lynch syndrome. That's an initial screening test. When that comes back positive, meaning that these proteins are missing in the tumor, that sort of raises a flag then that we are potentially dealing here with Lynch syndrome. The only way to confirm it then though is with genetic testing where usually it's blood, sometimes saliva, but usually blood will get tested for if the gene itself that's responsible for creating that protein, if that's affected with one of the mutations we see in Lynch syndrome. Now the genes that are affected by Lynch syndrome, they're called mismatch repair genes or mismatch repair proteins are the proteins that they make.

And those proteins are in charge of fixing little errors that happen inside the DNA. As a person ages, the body keeps continuously churning out new cells and errors happen in the DNA when that happens. And our body has a defense mechanism for that, which are these mismatch repair proteins that repair any errors that happen in the DNA. When the person has Lynch syndrome, some of these proteins are missing, which then can introduce more mutations and tissues that can then lead to tumors. In a roundabout way here, what I'm saying is that we do a universal screening test on the tumor tissue that looks for these proteins and when they are missing and that tells us, let's look for the genes to see if there's a Lynch syndrome there.

Scott Steele: So David, you are the director of the Weiss Center. Can you give the listeners an overview of the center? What does this encompass, what does this center do?

David Liska: The Weiss Center is really a group of individuals, physicians, genetic counselors, coordinators from many different disciplines. We all have an interest and expertise in taking care of patients with hereditary colorectal cancer syndrome. Now, our goal, our mission in the Weiss Center is to prevent cancer and make sure that nobody dies from colorectal cancer by educating our patients, by doing appropriate surveillance and surgery when needed, and also advance the field through research.

Scott Steele: David, one of the things that the Weiss Center has is a patient registry. What is that? Why is it unique and why is it important? What can it tell the patients as well as physicians?

David Liska: So our hereditary colorectal cancer registry, which are a big part of the Weiss Center, they were started about 40 years ago by Dr. Jagelman, a colorectal surgeon here at the Cleveland Clinic. And that's why they're named the Jagelman Registries. The goal of the registry really is to collect information about individuals with colorectal cancer and their families. This allows us then to continue monitoring and treating patients and their relatives, but also very importantly, learn more about the disease and potentially develop new treatments. At the beginning of this discussion when you talked about how colorectal cancer that's hereditary is pretty rare. We're talking about, FAP 1%, Lynch syndrome two to 3%.

Without having this registry where we can collect and families and the information on what they've gone through, and what we've found in them, you really can't figure out much about these diseases. Many of the genes that cause hereditary colorectal cancer we really discovered just by carefully collecting data on families participating in such registries. The registry is not just important to take care of patients who have them, but really to advance the field so that we can learn more about it and develop new treatments.

Scott Steele: So David, I know we only talked about two of the major ones being FAP and Lynch syndrome, but what's on the horizon as far as additional research or identifying and treating patients with hereditary colorectal cancers?

David Liska: So yeah, we continuously work on developing better ways to prevent cancer while the big important part of our Weiss Center and what we do for our patients is we don't only look to prevent cancer. We also want to maintain the optimum quality of life for our patients with hereditary colorectal cancer. So this includes developing and testing new drugs that can potentially prevent colorectal cancer and thereby, maybe prevent the need for surgery. But also at the same time, we're finding our surgical approach to be able to have minimally invasive surgery, or better care paths around the surgery to make the entire surgical episode less invasive and easier to recover from. We also continuously collect data from our registries to figure out which cancers we need to be screening for and what intervals and what testing modality is the best for a given syndrome.

Scott Steele: Congratulations again on what you are doing with the Weiss Center. What's a final take home message for our listeners here?

David Liska: So, yeah, as I started out, it's really important to know your family history. There's no way of knowing if you have a hereditary colorectal cancer syndrome or even if you don't have a hereditary cancer syndrome, to know what your risk is for developing colorectal cancer, without knowing your family history. It is understandable that some families don't like talking about conditions that afflicted their loved ones, but being aware of one's family history, especially if it affected more than just one family member, can point to a hereditary syndrome that can be tested for. And knowing that you have in this hereditary syndrome can then guide screening that can prevent cancer and save lives.

Scott Steele: Well, that's fantastic stuff. As everyone who listens to Butts & Guts knows, we'd like to wind up with some quick hitters. And David, I asked you four of the kind of standard ones already. So since you're a second guest on, we'll branch out a little bit and ask some new ones. So what's your favorite band or musical group?

David Liska: The Beatles.

Scott Steele: Britney Spears, fantastic. And what's a hidden talent that you have David that we're not aware of?

David Liska: I don't. I can yodel.

Scott Steele: Fantastic.

David Liska: Not really (laughs).

Scott Steele: And so I read a lot of people checking out new series on many different platforms out there. What's a series that we should check out, David, that you feel like, hey, our listeners there maybe you need to check out whether it's on any one of the different networks?

David Liska: Shtisel. I think it was a Netflix.

Scott Steele: It was absolutely on Netflix and a very good one at that. Although I think that that is in subtitles if I remember, right? And then, I talk about what's your favorite thing about Cleveland, but to wind up, what is one of your favorite places in the world to travel? You are from Austria, so what is one of your favorite places to travel?

David Liska: I'm particular to Italy. We used to go there every summer. It was a quick drive down from Austria and filled with great memories.

Scott Steele: Absolutely. And hoping the world will open up and we can all take these opportunities again, if possible. So to learn more about hereditary colorectal cancer, as well as the Weiss Center, please visit clevelandclinic.org/weisscenter. That's clevelandclinic.org/weisscenter. And remember Weiss is, W-E-I-S-S. That's W-E-I-S-S-C-E-N-T-E-R. You can also call the Weiss Center at 216.444.6470. That's 216.444.6470. And for information on colorectal cancer screenings, or to schedule a colonoscopy, please visit clevelandclinic.org/colonoscopy. That's clevelandclinic.org/colonoscopy.

And again, my listeners always understand, I see this all the time, but please remember in times like these it's important for you and your family to continue to receive medical care. And rest assured here at the Cleveland Clinic, we're taking all the necessary precautions to sterilize our facilities and protect our caregivers and patients. So David, thanks so much for joining us on Butts & Guts.

David Liska: Thanks so much.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.

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A Cleveland Clinic podcast exploring your digestive and surgical health from end to end. You’ll learn how to have the best digestive health possible from your gall bladder to your liver and more from our host, Colorectal Surgery Chairman Scott Steele, MD.
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