The connection between genes and colon cancer

MD Anderson Cancer Center
Date: 05-07-12


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Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas, M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing thelatest information on reducing your family's cancer risk. I'm your host, Lisa Garvin and our guest today is Dr. Eduardo Vilar-Sanchez. He is an Assistant Professor of Clinical Cancer Prevention here at M. D. Anderson and we are going to talk about the genetic implications of colorectal cancer. Well, welcome!

Dr. Vilar-Sanchez: Thank you, Lisa.

Lisa Garvin: Apparently, there are some genetic predispositions to colon cancer, correct?

Dr. Vilar-Sanchez: That's correct. We will say that colon cancer is a disease that affects general population, but one of the main risk factors to have colon cancer is familial cancer risk, so people that will, will see among their family members some aggregation of colon cancers and cancers also related with colon cancer, those individuals may be at a higher risk to develop colon cancer and they may be willing to check with their doctors to accurately estimate the risk, if the risk is above or not the general population, but yes.

Lisa Garvin: For the patients that we see at M. D. Anderson, about what percentage would have a genetic component to their colon cancer.

Dr. Vilar-Sanchez: It's difficult to estimate thinking about precisely of the population in M. D. Anderson because we are a tertiary referral center, but I will say that across the board, generally speaking, around 5% of the total of colorectal cancers arise on the basis of genetic, some genetic predisposition.

Lisa Garvin: And while we're talking about colorectal, let's kind of be clear about it. Are we talking not only about colon, but anal and rectal cancers as well?

Dr. Vilar-Sanchez: We're talking about colon and rectum. Anal cancer is a different disease so we're talking about colon and rectum.

Lisa Garvin: Now let's talk about the, the genetic mutations that we know about. There are a coupe of genetic, I'm sorry, let me start that from the top. So there are a couple of well known genetic mutations for colorectal cancer, let's talk about those and let's start with what we call FAP or familial aden... I don't even know if I'm saying it right, familial adenomatous.

Dr. Vilar-Sanchez: Adenomatous.

Lisa Garvin: Polyposis or FAP, let's talk about FAP.

Dr. Vilar-Sanchez: So FAP is an inherited condition that predispose individuals to have colorectal cancer. We will say that those people typically present with hundreds to thousands of polyps that are [inaudible] in the basically the upper and the lower GI tract. So they not only have polyps, which are the premalignant lesions that predispose, that will develop into colon cancer, they not only have polyps in the colon and rectum but also grow polyps in the duodenum and some extent in the stomach as well, but we'll see, we'll say that those individuals if the polyps are not removed, will develop by all means colon cancer, so the lifetime risk of an individual diagnosed with FAP, the lifetime risk of colon cancer is approximately 100% so at some point these people need to have remove the colon that happens usually after teenager age, I mean, and that's something that will vary some one cases to the other, it depends also on the type of mutations and obviously will depend on the counseling of the appropriate team which basically is formed by a gastroenterologist, genetic counselors, and the surgeons who will develop the best approach and will determine how extent has to be the surgery because there are different surgical approaches for total colectomy, but we'll, we'll say that those people need to have removed the colon at some point in their life sooner rather than later to avoid the development of colon cancer. This is an inherited condition, as you were saying very well Lisa, the form of inheritance is called autosomal dominance so is, it's going to be passed from one generation to the other from just one of the progenitors either to the father or the mother and the main gene that is involved in familial adenomatous polyposis is the gene called APC.

Lisa Garvin: Now this gene is it what a 50% chance that they'll pass this off to their offspring?

Dr. Vilar-Sanchez: Yes.

Lisa Garvin: Now say if there is no genetic history or people aren't aware of their genetic history, how would they know that they have FAP?

Dr. Vilar-Sanchez: That is an intelligent question. If there is no family history and there are some, there are important number of cases of people with familial adenomatous polyposis that have the mutation in a way that we will call it de novo, so they are the first people, the first time in the among the family that they develop the disease, who won't know, I mean, it's because the symptoms of the polyps are very generic. They may have diarrhea sometimes they present with some bleeding. Obviously, if there is some bleeding and the blood is on the stool, those people will go to the primary care physician or a gastroenterologist and will get the colonoscopy, but until there is no development of symptoms such as bleeding, obstruction, or diarrhea, we won't know because, again, these people are, the majority of them are going to develop colon cancer before the average age of screening with colonoscopy which is 50 so, yeah.

Lisa Garvin: Because it seems to me that maybe somebody would say okay well, my father or grandfather had colon cancer, but they're not necessarily connecting the dots genetically. Do you know what I mean?

Dr. Vilar-Sanchez: Yes, for sure. I mean in particular, in the particular case of familial adenomatous polyposis, it's, it's relatively more infrequent that they will have grandfather with colon cancer and they wouldn't know because they tend to present with cancer at a younger age and when I say in a younger age it's something like 30's or even 40's that will raise a, a, the red flag for them to go somewhere and to, to seek expertise advise. But yes, I mean, obviously familial, I mean, looking at the picture, the whole picture of family members is something that may prone to people to find out more and they should ask their primary care physicians so that's, that's an important thing on, on average risk people around age 40, people they should approach their primary care physicians and, and say well, I am interested on estimating my risk of colon cancer and the primary care physician, and this is not something fancy just with the standard approach normal interview they should be able to roughly assess the risk of that individual person. And when I am saying assess the risk, it will be to account for that information is there any family member that has been diagnosed with colon cancer or other related cancers, by the way, uterine cancer and things like that are also linked to other familial conditions that we will touch base in a moment such as Lynch syndrome then other factors such as what type of diet are you doing, I mean, is your diet rich in meat or red meat or processed meat? Is your diet low in vegetable intake? Is your diet low in fiber, I mean, in fiber? Those are kind of some of the environmental risks, typical environmental risk factors. Vitamin D intake, folate intake, again, low diets on that have a higher chances to develop colon cancer and this is general environmental estimation. Other risk factors is there any personal history of adenomas for people that have had already a first screening colonoscopy after age 50? Do you have any personal history of colon cancer? That is also important. Some of our audience may not know that survivors of colorectal cancer need more intensive surveillance than the general population because they are also at risk of secondary colorectal cancers and also an especial population is people that have been diagnosed with IBD - inflammatory bowel disease. Those are also at increased risk for colon cancer so and that's something that any general practitioner, primary care physician will do on a regular, on a regular visit and just estimate roughly do these
people need to get colonoscopies before age 50 or do these people need to be referred to a gastroenterologist or do these people need genetic counseling? So.

Lisa Garvin: And let's talk about Lynch syndrome, you brought it up earlier that's another genetic predisposition. Whatis Lynch syndrome?

Dr. Vilar-Sanchez: So Lynch syndrome is has been known before as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. This is another genetic condition that predisposed people to develop colorectal cancer apart from FAP, which are the, the
two main syndromes predisposing to colorectal cancer. Why we are using now Lynch syndrome instead of HNPCC? Because we have learned that these people also develop polyps so it is not nonpolyposis now. We've, we have found that people diagnosed with Lynch syndrome also grow polyps. They don't grow polyps in the same number as people with FAP. They will have several polyps not hundred or thousands, but also this is a genetic condition that is based on mutations in what is called mismatch repair genes and is not, again, going back to the FAP comparison, it's not only one gene there are four genes, which are MLH1, MSH2, MSH6, and PMS2 roughly, a mutation in one of those four genes predispose individuals to develop colon cancer and therefore being diagnosed with Lynch syndrome. It's another autosomal dominant condition as FAP and not only put people at risk to develop colon cancer also put females in risk to develop endometrial cancer and that is something that we have developed a special expertise here in M. D. Anderson as well. Other cancers related with the diagnosis of Lynch syndrome and people are also in risk for that diagnosed with Lynch syndrome are urinary tract cancers and ovarian cancer as well, although the risk for those are lower compared to colorectal and, and endometrial cancer.

Lisa Garvin: Now as far as screening goes, if people know they have this genetic predisposition, how does that change their screening guidelines?

Dr. Vilar-Sanchez: Oh, it change, I mean, first of all, if someone has a family member or a relative that has been diagnosed with Lynch syndrome, they should get, they should be referred to a genetic counselor so a cancer genetic clinics. What is the procedure that they need to get screened, if, for example, in the case of colon cancer if they need to have colonoscopy, if they need to start with colonoscopy at a younger age, so let's say instead of 50 years of age if they need to get colonoscopies at the age of 40, you know, that the general population that do not have polyps after the first screening colonoscopy need another one ten years later, it is not the case in these people, eventually they will need to have another colonoscopy sooner, sooner than that and the frequencies also that can be more or less tailored from one family to the other depending on the ages and diagnosis on the frequency of the cancers. So it has a lot of potential to change screening recommendations and also further interventions, so...

Lisa Garvin: And given what we know about these genes, we know they exist and we know the mutations, is there any sort of chemopreventive measures that can be taken with these?

Dr. Vilar-Sanchez: Unfortunately, there is no chemo prevention with drugs at this point for Lynch syndrome that's one of the things that we are trying to do on a research basis. There are some studies that have been released recently about the beneficial effects of aspirin to prevent colon cancer in Lynch syndrome population. Right now, there are several clinical trials that are, are, I will say that are waiting to be activated to understand better what is the best agent to use and what is the best dose and the best sequence or schedule for those drugs. So there is no hard recommendation at this point about chemoprevention drugs. On a research basis that is basically what I am trying to do on, on my, on my research program on my lab, we're trying to identify new targets in Lynch syndrome patients and to see if we can find a drug toward those targets that we can utilize to prevent the development of colon cancer or other cancer and there is also other groups here in M. D. Anderson that are working with Lynch syndrome families developing chemoprevention to strive to use for endometrial cancer as well.

Lisa Garvin: What about targeted therapies once a person is diagnosed? I mean are you working on therapies that find those genetic mutations or those cell receptors?

Dr. Vilar-Sanchez: Yeah. That's something part of my interest in the research arena. We are trying to identify new targets in colorectal cancers that arise in patients diagnosed with Lynch syndrome that are sometimes directly related with the mismatch repair genes or the targets are related with the instability that is, that is introduced in the genome by the mismatch repair deficiency, and although we don't have any final recommendations yet, we are in the process of developing all of this. We, we have several lines of research to develop a specific targeted interventions in these, in these cases.

Lisa Garvin: Great. Thank you very much.

Dr. Vilar-Sanchez: Welcome.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact Ask M. D. Anderson at 1877-MDA-6789 or online at Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.

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