Transcription:
Lynch Syndrome: Early Detection is the Key

Melanie Cole (Host):  Lynch syndrome is an inherited condition that gives a person a higher risk of cancers of the digestive tract, gynecologic tract, and other organs. My guest today is Dr. Thomas Slavin. He's a clinical geneticist and assistant clinical professor in the department of medical oncology and therapeutics research at City of Hope. Welcome to the show, Dr. Slavin. A lot of people, this is a new one for some people, what is Lynch syndrome?

Dr. Thomas Slavin (Guest):  Lynch syndrome is an inherited predisposition to getting colorectal cancer and other cancers from your family and so it's in our mom and dad’s genetics. It affects probably somewhere around 1 in 500 people per everyone. It's almost as common as, or at least in the ballpark of, similar syndromes like BRCA1 and BRCA2 that people that commonly think of when they think of Angelina Jolie now, who made those really famous. It's something commonly tested for people that get colorectal cancer and we see it all the time.  

Melanie:  So, then, what are some of the signs if you're looking at specific cancers like colorectal cancer or some of the other digestive cancers? Where does Lynch syndrome fit into that picture? Is there now a genetic test? Does the family get tested? Tell us about that.

Dr. Slavin:  Yes, there has been a recommendation that literally every single person that get colon cancer should have at least a tumor test that can hint whether that person may have Lynch syndrome or not. Now, that is not being done currently at all centers; however, in a lot of centers it is. When the test is done, if it comes back abnormal, a lot of people get picked up that way and so they get referred to someone like me to try to figure out if it's really from their mom or dad's genetics. Other ways would be if there is a really strong family history of colon cancer, especially on one side of their family, there's criteria that's called the Amsterdam 1 and Amsterdam 2 criteria to pick up those families. In Amsterdam 2, it picks up even more families because in addition to colon cancer, there is the huge risk for other cancers, particularly for women, uterine cancer. That’s the other big one where almost 70% of women with Lynch syndrome will get uterine cancer.

Melanie:  So, like BRCA1 and BRCA2, Dr. Slavin, people hear about those as you say in the media. People don't understand that everybody has that gene. It's the mutation of the gene that you have or not, so is this similar that way? We're all going to have these gene, the MLH1 and such? And, it's a mutation? Or, do you just not have the gene if you are not at risk for this?

Dr. Slavin:  Good question. Yes, these are exactly like BRCA1 and BRCA2. So, breast cancer gene 1 and breast cancer gene 2. Those were the first genes discovered putting people at a really high risk for breast cancer. Breast cancer gene 1 was the first one. And, at a similar time in genetics, we were identifying a lot of families at high risks for other hereditary cancers syndromes. The other classic syndrome, at that time, was a kind of a friend of Lynch syndrome, in a way. It's called familial Adenomatous Polyposis Syndrome. It's, in a weird way, almost the opposite of Lynch syndrome  because those people get thousands of polyps all through their colon, but the family histories are so striking that it was one of the first other cancer syndromes to get picked up along with BRCA1. Then, Lynch syndrome was identified many, many decades ago, at least by families, and some of the work by Dr. Lynch, who the syndrome is named after now, was really collating those families trying to figure out was there a risk in the family thinking that it was due to a gene. Then, as genetic technologies got better over the decades, being able to identify some of the genes that you brought up, MLH1 and MLSH2, and then there's another gene, MSH6 and PMS2, and some other variations thereof that affect the gene. Now, you are 100% correct. We all have these genes we all have MLH1. We have two copies:  one copy came from our mom; one copy came from our dad. In the majority of people, MLH1 works totally perfect. Its job is to repair DNA. It’s very similar to how BRCA1 and BRCA2 work. It’s a little bit different pathways but it is in this pathway called "mismatch repairs". It just tries to fix our DNA. If there's a problem in that gene, it's almost always inherited from a parent and that does set up for Lynch syndrome. If one gene is not working correctly, you still have a totally normal working copy. You know, the theory is you don't develop the cancer:  the colon cancer ,the endometrial cancer, or whatever cancer we're talking about, until that second copy in that same cell has a problem. So, that's why you see early onset of cancer. I digress a little bit in the sense of talking now about that "the two-hit hypothesis". This was an old cancer hypothesis that's been around a long time by Dr. Knudson and whatever first two is, our cells have all these little proteins that try to fix our DNA. If something happens with one of those copies of the actual fixer itself in the DNA, you are fine because you still have a backup copy. However, the second time or the second hit, essentially, of your other working copy of that same little gene, so we're talking about MLH1. If one copy stops working in your 40s and then in your 70s, the second copy in that same cell line stops working, then you develop colorectal cancer at 70. What happens in Lynch Syndrome and similar to the other hereditary cancer syndromes, because they're mostly tumor suppressor syndromes involving tumor suppressor genes, so trying to keep tumors at bay. You're born with one strike against you. So, you're born and you already have one strike against you. Instead of getting that second hit when you're in your 70s, that second hit really comes in your 30s or 40s in that same cell line. That's why you see really early onset cancers that can be really striking in these families.

Melanie:  So, are there some screening options for Lynch Syndrome? Do you want people to have more colonoscopies than the average person or testing for H pylori? Is there anything that people can do prophylactically to help themselves with these strikes against them, as it were?

Dr. Slavin:  Yes, absolutely. At City of Hope, as you know, we are a national comprehensive cancer network center, so we participate in the guidelines--national comprehensive cancer network guidelines--which have really, in a sense, become kind of global guidelines for these kinds of things. I mean, definitely in the United States but very international adopted guidelines. You know, what I say to my patients with Lynch Syndrome is, our goal is to keep you free of cancer now. You do not need to be theoretically dying of cancer, at least some of the cancers that we can prevent now. There are clearly some cancers that are extremely difficult to prevent in 2016 or even detect early that are apart of Lynch Syndrome, such as the very low likelihood of getting brain cancers and pancreatic cancers. However, even our detection of those is getting better and, overall, they are a very small percentage like 1% to 5% of all the people with Lynch Syndrome. The major cancers, the most frequent that we see such as colon cancer, endometrial cancer, ovarian cancer, stomach cancer, these we should be pretty proactive in our ability to keep people cancer-free. What we recommend for people with Lynch Syndrome is to start getting colonoscopies between 20 and 25 or, 2 to 5 years prior to their earliest point cancer in the family. We recommend, instead of the average U.S. risk person to start colonoscopies at 50 and then every ten years, we recommend starting really at that age that 20 to 25 and then every one to two years. So, it's very tight colon surveillance. Now what that means is it takes years for a colon polyp to turn into cancer and so we should be able to keep someone cancer-free because, theoretically, we should be able to pluck out any polyps that are there prior to it developing cancer. If you're getting very frequent colonoscopies, really, I mean, in theory, we should be able to keep you nice and cancer-free. Now, there's other screening that comes along. We also recommend doing the scope through the mouth and looking at the stomach. Now, the stomach cancers and Lynch Syndrome are a little bit later in onset, so we don't usually recommend that till 30 to 35, unless there's some really early stomach cancer in the family. We may dial it down. Yes, treating H pylori, as you brought up, is the big one. For the uterus and the ovaries, we recommend, right now, the uterus, that consideration of removing the uterus, usually at 35 to 40 or at the end of childbearing in addition to removing the ovaries at that time. In particular, because with ovarian cancer, there's no effective screening, unfortunately, in 2016. That's really held up in studies although this may change over time as well. But, at least right now, to keep people free of ovarian cancer, that's the recommendation. Then, we also perform urine screenings once a year just to see if we can pick up any abnormal cells in the urine that might indicate some of the urinary tract cancers that people can get. Pancreatic cancer, there's some research screening that's going on and we tend not to do that unless there's a family history of pancreatic cancer. Now, we don't change breast cancer surveillance for Lynch Syndrome individuals because this is not thought to be strongly linked to breast cancer. Other than that just making sure that there's nothing going on at least once a year, at least not anything unusual like new headaches waking somebody up from sleep every night; things that could be concerning for a brain tumor. I also do a full neurologic exam when I see people just to make sure everything is working like it's supposed to. I mean, doing that kind of screening on everyone, you know, a planned screening which is really, again, per the NCCN guidelines is pretty good and the goal is to keep people nice and healthy. Personally,, I even have a Lynch Syndrome screening clinic and a surveillance clinic. This is literally what I do in the clinic. So, our goal is to keep people cancer-free and to help protect their family.

Melanie:  What great information, Dr. Slavin, and last question here:  who do they go to see to get all of these screenings? Do they come and see a geneticist? Do they go to an oncologist right off the bat? Who do they go to see?

Dr. Slavin:  I think the most important thing is to have an open dialogue with your treating doctors. That's step one. Step two is really finding someone that has experience in Lynch Syndrome. You know, you don't want necessarily to be the first patient time to someone's ever had with Lynch Syndrome. You want to try to get to somebody that has some expertise. In most places, that would be most cancer centers or really big hospital systems in general because, again, a lot of people with Lynch Syndrome don’t have cancer yet. They may not be plugged into a cancer center at the present time because they just have a family history of cancer. They were just identified with the genetic change that put them there and put them with the molecular diagnostics of Lynch Syndrome. Usually, the person that does the genetic testing, if they've had genetic counseling through a genetic professional, such as a genetic counselor or a clinical geneticist. Those people, if they don't do the screening program themselves, know who does in the community. That's an excellent place to start. Start with the centers that do the genetic testing. Now, there are a lot of patients getting tested through their regular doctors for Lynch Syndrome. I think a good question is, okay, so if it does come back positive, who are you going to send me to? Because, you know, it's good just to have that knowledge in hand prior to always doing that testing. I do always recommend, as well as many guideline committees, having genetic counseling prior to having this testing.  It also makes it a very smooth flow where, if you do get identified with Lynch Syndrome, now everything's already in motion. You can be referred immediately to the right specialist so the next set of questions can all be answered about your management and surveillance. In general, I would say most major cities, now in today's day and age, because Lynch Syndrome is common enough, will definitely have experts in Lynch Syndrome. A lot of times, there are actually gastroenterologists just because they're the ones doing a lot of the screening. You know, I will say though, you heard the whole list of cancers that I put out and hopefully that got across that this is a very constitutional systemic kind of condition. You can get a lot and besides just the colon cancer, there are a lot of other things we would recommend screening for. That's why it's just important, even if you do end up at a gastroenterologist, making sure that they are still thinking about asking you if you have had any new headaches or doing a neurologic exam on you, doing the urine screening, thinking about uterus and ovaries for women so that your care is being handled appropriately. There are also a lot of patient sites out there as well that can help, especially in our age of information.  For instance, we just did a hereditary colon cancer family day where we had a lot of families with Lynch Syndrome come to City of Hope and we did an educational day for families patients and their families. It was that put on through one of the organizations nationally that it is the patient advocacy kind of an organization that connects families with Lynch Syndrome as well. There are some of those out there that are good sources of information because not everyone has access to the National Comprehensive Cancer Network guidelines, obviously, but everybody has access pretty much, in today's day and age, to internet and can get in touch with some of these organizations.

Melanie:  Sure. Well, what a fascinating topic and such great information. I applaud all the good work that you are doing, Dr. Slavin, at City of Hope. Thank you so much for being with us today. You're listening to City of Hope Radio. For more information, you can go to city of hope.org. That's city of hope.org. This is Melanie Cole. Thanks so much for listening.