Lynch Syndrome

So, in general Lynch syndrome is a multi-- what we call multi-cancer syndrome. So, while colon and endometrial cancer are the ones that carry the highest risk for Lynch syndrome, in fact it’s a multi-cancer syndrome where there are other organs that have also carry a high risk of cancer: from ovaries, to the rest of the GI tract, to the urinary tract. So, it has to be approached as such, as a multi-cancer syndrome. The Lynch syndrome is due to mutations in a set of genes that are called mismatch-repair genes. And their job is really fixing particular types of defects in the DNA daughter chains that are created. Those defects do happen on a regular basis as daughter chains keep getting created, our body’s not that perfect, but our body has those mechanisms to really fix those defects. When those genes are mutated, they cannot do their job of fixing those errors, and those errors start propagating in the new cells that are generated, becoming cells that are not well controlled and that’s how cancer evolves in Lynch syndrome. In general, cancers do develop fast in Lynch syndrome, even though the prognosis in general is better, but the key thing for Lynch syndrome is very early diagnosis so that we can catch cancers early. In general the cancer risk varies for colon, for instance, in Lynch syndrome, you can go from 12% for one of the mutations call PMS-2 to about 50% for the more common-- or the genes that carry a higher risk. So, there’s quite a bit of variability. So, it’s important for us to know which is the particular gene that is causing Lynch syndrome. And the other types of cancers we talk about also vary depending on the type of gene. For instance, the endometrial cancers have a high association with MSX-6, another mismatch repair gene. So, those are important details so Lynch syndrome as a whole is an entity, but it has a lot of flavors and often they depend on the particular gene that is affected. And, when it comes to Lynch syndrome we’ve identified individual who carry the genetic defects. We do have surveillance strategies, chemo preventive strategies, and also surgical interventions that can prevent cancer. For colon, colonoscopy is a well-accepted procedure that does help prevent colon cancer. It has to be done very-- every one to two years to make sure that we catch the cancers early enough because as we said those cancers evolve fast. For endometrial and ovarian cancer risk often it comes down to discussing hysterectomy after childbearing age most of the time. So, they are interventions that are really tailored to the patients. Aspirin as a chemo preventive agent has been found to be a very effective agent when taken in high doses. So, there are studies going on right now trying to identify lower doses that have a significant preventive effect for cancer too. So, there are things on the horizon and the chemo preventive world too. So, in general, we have learned a lot about Lynch syndrome, we’re still learning a lot, but we do know how to effectively prevent cancer in Lynch syndrome, and that is why it’s so important to diagnose it. And that’s why it’s important to diagnose it in individuals who never had cancer before so we can actually prevent the development of cancers.

 

We need to make a lot of noise. We just need to get the word out and people need to talk about it. And there need to be more Lynch Syndrome chapters and Lynch Syndrome International, because if one in 279 people have Lynch syndrome, and 95% of them don't know, that's a lot of people who are going to be hurt, or could be hurt, or could undergo, you know, unnecessary pain and suffering.

I was reading through the paperwork and read that I had Lynch syndrome, but I had not been told. And I had no idea what that was. So I looked it up, which was always a bad thing, but it was evening. So my husband and I looked at information about Lynch syndrome and then called the next day to say, “what is this?” And I was not told that I was being tested. That apparently it's some routine tests that's done, only genetic testing is not routine to me. So I would have been less caught off guard I think if I had known and had signed consent to say yes. Now, it may have been written into consent, I have no idea. And I haven't followed up on it because, bottom line is, I have it and I can't change it, so.

I know there are guidelines through the NIH, but Lynch is still being discovered in a lot of ways. We haven't quite figured out exactly how often somebody needs to get screened in order to prevent these different cancers from forming. So it needs to be-- you need to consider the guidelines but add a little bit of balance based on your situation and how you feel about yourself and what your lifestyle is.

You know, it’s one of those things. For as much as we know, we don't know. And I think that everybody's still trying to figure this thing called Lynch syndrome out. Because it's like a moving target. It's changed a lot in the time period when I was first diagnosed, in terms of what cancers they think are affiliated with it and what the percentages are, chance of you getting it. That seems to have slid up and down some.
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And I'll keep an eye on it. I keep going to a specialist who specializes in Lynch syndrome, every couple of years, to see if there's anything new on the forefront, new discoveries. That, plus the genetic counselors seem to know, too. So it's a work in progress, I think, for everybody.

How has it changed for you as a clinician to give people a Lynch diagnosis?
Right, so it really has evolved tremendously from 10 years ago, or so, where having a Lynch syndrome diagnosis and the particular gene that was causing it made little difference to us and we all thought that they all had a very high risk of cancer and therefore they really had to be counselled in a very similar way, to now that we’ve learned so much more about the specific risks by gene that actually we’re starting to propose to no longer talk about Lynch syndrome in general but saying emolage 1 Lynch syndrome, emissige 2 Lynch syndrome, emissige 6 Lynch syndrome, because what it means having one mutation versus another is very different. And that’s what we’re trying to tell our patients and that’s why little by little we’re tailoring more surveillance and recommendations to their own specific mutations. That is really more of a personalized approach, and as we learn more, we’re really developing surveillance recommendations more tailored to those specific genes. And we’ll hear more. As we learn more about modifiers and other things probably be able to narrow the choices for every single person even more. So again, what we were saying several years ago, based on the knowledge at that time, has changed quite a bit now, and I’m very sure in a few years it’s going to be very different from what we are seeing today. So, I think that emphasizes the importance of keeping in touch with cancer genetics programs for patients, because what we told one may change. It’s extremely likely that it’s going to change in the future, and so they can benefit from more updated information.

Cause it is not a guarantee that I am going to get cancer. It's not a guarantee I'm going to develop one of these, but I kind of take it to be that way. It's going to happen. The goal here is to find it faster than otherwise, giving me better chances to treat it, to fight it. You know.
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Just the volume of more screenings that it means for me as a female, you know, spilling over into ovarian, endometrial, some bladder. All of this stuff kind of connected in the reproductive system. Those screenings are-- I don't want to say more difficult than colon and stomach, but not as certain in the outcomes of them. And still can be pretty uncomfortable and difficult. And so it adds a bigger list of things for me to tackle.

If I was facing a 20% increase in the risk of my having cancer, but it might or might not happen, I think that probably would affect me more. But since I can go get a colonoscopy, and largely be free of the worry of whether I might get it or not, I believe I'm kind of free of that. So no, it has not affected my own sense of mortality or risk or concern. I don’t think-- I don't have a concern with that. I will simply get my regular, just like getting my regular tetanus booster or whatever comes up. I'll do that one when I need it because it's so predictable.