Genetic Testing

Dr. Roy Jensen: Welcome to Bench To Bedside, a weekly series of live conversations about recent advances in cancer from the research bench to treatment at the patient's bedside. I'm Dr. Roy Jensen, Director of The University of Kansas Cancer Center, and with me is Dr. Eric Rush, clinical geneticist at The University of Kansas Cancer Center and Children's Mercy Hospital. Thanks to our increasing knowledge of cancer genetics, we know that anywhere from 5-10% of all cancers may be hereditary. These cancers are caused by inherited genetic mutations or flaws in genes that control how our cells grow and divide. Such genetic flaws can lead to disorders that increase our risk of developing cancer. With genetic testing for cancer risk, we can assess whether someone with a family history of disease has one of these genetic mutations. For example, many people are aware that the risk of breast and ovarian cancer is significantly increased when there is a mutation in the BRCA1 or BRCA2 gene. What people may not know is that there are many other genes that can influence their risk for a wide variety of different types of cancer. Dr. Rush, could you please explain why some individuals have an increased likelihood of developing a particular cancer based on their genetic makeup?

Dr. Eric Rush: Absolutely. And thank you for having me on this morning, Dr. Jensen. It's known that the majority of cancers are what we call sporadic, meaning that they happen for reasons of environmental exposure, the aging process, a lot of things that we maybe don't understand quite yet. But what we also know is that there are a percentage of patients who do have one gene or sometimes a combination of genes that are not functioning correctly. And when those genes don't function correctly, then there may be a predisposition to certain types of cancer. Sometimes it's just one type of cancer. Many times it's multiple kinds of cancer. For instance, the audience may know somebody who has said that they have inherited the breast cancer gene. And while that's not exactly true because those people haven't inherited a new gene or an additional gene, what they have inherited in those cases is a change to an existing gene which gives them an increased risk for, in that case, breast cancer or potentially other kinds of cancer. Over the last 50 years or so, we've noticed that there are increased predispositions to a number of different kinds of cancer. And over the last 10 years, we've discovered the molecular lesion, the reason why people have a number of these kinds of cancers. And so for that reason, it's a very exciting time to be involved in cancer genetics.

Dr. Roy Jensen: So why would it be important for someone to know if they're at increased risk for cancer?

Dr. Eric Rush: That's a great question, and it depends on the person. We all may have some different motivations for why we might wanna know that we're at increased risk for cancer. Many patients who are coming in, especially those who already have a diagnosis of cancer may be concerned about what is the likely natural history of their cancer? What's likely to happen to them? Many of them are also concerned about what can they do to reduce the risk of other types of cancer? These are very common motivations for people who are ... who have cancer or maybe feel that they're at increased risk for cancer. We also find that many people who come in for testing are also concerned about family members who may be at risk. In particular, people who have children may be concerned about the fact that they might have passed on, inadvertently, a predisposition for cancer to their children. And that's also a very common reason for people to seek this sort of testing. And then lastly, we occasionally do see patients who mostly have altruistic motives for doing this. They want to contribute to human knowledge. They want us to learn more about cancer through their own experiences. And I feel that these are all very reasonable reasons why a person would want to know why they have an increased risk of cancer.

Dr. Roy Jensen: So there are many different types of cancer that can be caused by inherited mutations. Let's focus on colon cancer.

Dr. Eric Rush: Mm-hmm (affirmative).

Dr. Roy Jensen: One of the risk factors is a family history of the disease. Can you share some insight on the common inherited colorectal cancer syndrome?

Dr. Eric Rush: Absolutely. I tend to like to put things into big categories that helps me understand them, and I think that helps patients understand them. I lump colon cancer into two main categories. And the first category and the one that's probably a little better known is one that we call polyposis syndromes or polyposis disorders. And these are patients who have sometimes tens of polyps, sometimes hundreds of polyps, and we know that this tendency to develop polyps also gives a tendency to develop cancer in those polyps. And there are a number of different genes that can cause polyposis syndromes, and the polyps can look a little different. The polyps can be of different numbers, and there may be other risks that are associated with a person having lots of those polyps. But it's known that there is a high risk of people with those polyposis syndromes eventually developing cancer. In some cases, that risk can be virtually 100%. And so for that reason, it's important for us to know if a person has a polyposis syndrome, and if so, what type? The second category of colon cancer that I think about is one called Lynch Syndrome. We used to call Lynch Syndrome a hereditary non-polyposis colon cancer. That's not exactly true because people with Lynch Syndrome do develop some polyps, but just not as many. It's more than in people with Lynch Syndrome, when they do develop polyps, much more likely that those polyps are going to develop into cancer. That tends to be more of the problem with people with Lynch Syndrome. Interestingly, Lynch Syndrome is also incredibly common. We think 1 in 300 people have Lynch Syndrome, and most of them don't know that they have it. And if I might, I would like to put in a plug for Lynch Syndrome Day, which is on March 22nd. And we'll be having an event at the KU Cancer Center that I think everybody is extremely excited about raising awareness for Lynch Syndrome and supporting people who are known to have that condition. So those are the main conditions that I think about with colon cancer. Of course, you can get into a lot of details here, but I think for our audience, I think it's important to know that those are the two main reasons why a person would have colon cancer.

Dr. Roy Jensen: Okay. What would you say it means to be at high risk for colon cancer? And what are some of the groups that are at high risk?

Dr. Eric Rush: Mm-hmm (affirmative)- Also great question. So all of us are at some risk of having colon cancer just by virtue of being human. We're imperfect, and so we have those risks of having cancer. And in people who are not at particularly high risk or who are not known to have a colon cancer predisposition, the risk is about 4-5% we think. Little higher in men than in women, but it's about 4-5%. People with these predisposition syndromes, depending on what type you have, may have an increased risk of as low as 15-20%, which is still three times the ... three to four times the average, to some people who have a risk of 100%, or essentially 100% of having colon cancer and everything in between. We would view all those patients at being high risk for colon cancer whether you're 15% risk or 100% risk. But I think we can all agree there's a big difference between 15% and 100%, and so for that reason, what we do about those conditions is quite a bit difference. For the person who's at 15% risk versus the person who's at virtually 100% risk.

Dr. Roy Jensen: Mm-hmm (affirmative)- So if you're just joining us, we're talking about the genetics of colon cancer and how to identify people who are at higher risk for this disease. And today we have joining us in the studio for his international stage, screen, and Facebook Live debut, Cameron Poindexter. And he's here to take your questions. Remember to share this link with people you think might benefit from our discussion, and use the hashtag #BenchToBedside. So how do we care for those who are at high risk for colon cancer? What do we actually do different for them than we would someone average risk?

Dr. Eric Rush: Quite a lot actually. So those of us who are at average risk will get our screening colonoscopies when we turn 50, and if we do well, every 10 years thereafter. For some of us that may be the end of it. But for people who are at high risk of having colon cancer, we often will start those screening colonoscopies quite a bit earlier, in some cases even during the juvenile and adolescent years for people who are extremely high risk for colon cancer. But in other patients it might be in young adulthood. But surveillance of the risk of colon cancer is one thing that we definitely do. One thing that people might not be aware of is that people with a high risk for colon cancers are often at high risk for other tumors as well, and it's equally important for us to understand, number one, what tumors you're at increased risk for. Because it might not be obvious that people with a certain type of polyposis are at high risk for gastric cancers, but we know that and so we screen them accordingly. Whereas it's also maybe not obvious to that to the people with Lynch Syndrome, or women with Lynch Syndrome I should say, have an increased risk of endometrial cancer, a type of uterine cancer. And so we screen for that as well. So it's screening the colon itself, and then it's screening other organs that we know are at risk. Because we don't want a person with a high risk of colon cancer to have colon cancer of course, but we also don't want them to have other cancers either. Occasionally we do things like prophylactic surgeries. If a person is known to have an extremely high risk for a condition, sometimes it's reasonable to consider surgery to reduce that risk. That's not for everybody, but in some cases it can be reasonable to do. And then lastly, there is a lot of discussion about the use of what we call chemo prevention for polyps. Can giving certain medications reduce the risk of having polyps or reduce the progression of polyps to colon cancer? And there's some evidence that says that it does, even though that's not ... the dose and the frequency are not completely nailed down as far as that's concerned. So there's really quite a lot we can do for people that we know who are at a high risk for colon cancer to make sure that if they do have cancer, we catch it very early. But hopefully they don't have cancer at all because of these surveillance techniques.

Dr. Roy Jensen: Mm-hmm (affirmative)- So that can be a lot of information for a patient to take in. Could you tell us about the role of genetic counseling in conveying this information to the patient?

Dr. Eric Rush: I'd love to. The genetic counselors make my life a lot easier. That is the way that I would start that out. So genetic counselors are genetics professionals who deal with helping patients understand things like their genetic risk and their genetic testing and also to provide counseling and support for those patients when that information is available. What genetic counseling appointment will generally consist of is a lot of information gathering. So a counselor may be interested in family history, in a person's personal history, and we'll put that together into what's called a pedigree. It's kind of a graphical way to express that information. And we'll ... In conjunction with a medical oncologist or geneticist, we'll make decisions as far as what genetic testing and what course of action is appropriate for a patient. And then once that information is available, then that counselor is very skilled at giving that information to the patient in a way that is comfortable for the patient and helps walk them through that process where overwhelming information can be a little more approachable.

Dr. Roy Jensen: Mm-hmm (affirmative).

Dr. Eric Rush: So genetic counselors are really valuable in the management of patients with a high risk of any cancer, not just colon cancer of course.

Dr. Roy Jensen: So many people are concerned about the release of their genetic information and the privacy aspects of this. Could you tell us a little bit about that and how those concerns are allayed?

Dr. Eric Rush: I'd like to. The framework we have is not perfect, but we do have a good framework for protection of genetic information. So many patients may be familiar with HIPPA. And so HIPPA governs the privacy of health information, and genetic information is subject to that. So we keep the same controls on genetic information as we would any other health information to make sure that that information is private. So the patients shouldn't worry that that information is going to inadvertently fall into the wrong hands. In addition, there is a law called ... we call it GINA or the Genetic Information Nondiscrimination Act of 2008, and this is a law that prevents the use of genetic information for discrimination for employment or for health insurance. This is a very important law to protect patients who may have genetic information that they would consider themselves at risk. And so they can't be discriminated against for those things. So GINA is not a perfect law, but it took a very big step in the right direction for protecting patients for health information. So if patients are very concerned about that, I definitely encourage them to take those concerns up with their genetic professional or their oncology professional so a further discussion can happen.

Dr. Roy Jensen: Mm-hmm (affirmative).

Dr. Eric Rush: It's very important.

Dr. Roy Jensen: So if you're just joining us, we're talking about the genetics of colon cancer and how to identify and care for people who are at high risk for this disease. And Cameron Poindexter is here in the studio to take your questions. Do you have any questions for us, Cameron?

Cameron P.: At the current moment we do not have any questions, but if you do have a question, please feel free to comment in the section below and I will be monitoring it and we'll have the doctors answer the question for you.

Dr. Roy Jensen: Alright. Well thank you, Dr. Rush.

Dr. Eric Rush: Thank you.

Dr. Roy Jensen: That's it for today. We'll see you next week, Wednesday at 10 a.m. Thank you and good day.