Hear a Patient Power interview with Amie Blanco, a genetic counselor in the UCSF Cancer Genetics and Prevention Program at Mount Zion, discussing screening and preventive measures for hereditary colon cancer.
Hello and welcome to Patient Power. I'm Andrew Schorr. We are happy that this is sponsored by UCSF Medical Center as we connect you with leading experts related to very important significant health conditions.
Today we're going to talk about colorectal cancer. This is, I believe, the second leading cause of cancer death when you take colon, rectal cancer and other related cancers. My mother died of it at 77 years old, and it affected our family a lot. So the question is, is there a genetic connection? How do you figure that out? If there is, what do you do about it?
Our guest today is Amie Blanco. She's a genetic counselor in the Cancer Risk Program at UCSF, and she specializes in helping families with this concern. Amie, thank you so much for being with us.
It's my pleasure. Thank you for having me.
We have many, many people who are affected by colorectal cancer. What percentage is a situation where there may be a genetic culprit, if you will, or at least a risk? How do you identify that?
Let me clarify some terms first, Andrew, for our listeners.
First, all cancers are in fact genetic, meaning all cancers occur due to the buildup of genetic mutations in a single cell that eventually became a cancer. What we focus on here are individuals who have hereditary risk for cancer, meaning they're born with a higher chance to develop cancer compared to their neighbors or their coworkers.
It doesn't mean they'll get it, but they're at higher risk of it.
Right, they have a higher chance, correct. In general, the vast majority of all cancers are what we could consider sporadic. They happen because of increasing age, maybe environmental exposures, and also a component of luck to be honest with you, but about five to ten percent of all cancers will in fact have a hereditary component meaning a gene trait being passed down from parent to child. In colorectal cancer there is also a third category. So we have sporadic cancer, we have this hereditary cancer, but there's also a third category that we call familial colon cancer, and this is where there are multiple individuals in a family with colon cancer, but it is not caused by a genetic mutation in a gene that we currently know about that we can do a gene test for.
In familial colon cancer we see that the risk for colon cancer in somebody's lifetime approaches perhaps 20 percent. In hereditary colorectal cancer, however, the lifetime risk for colon cancer can be as high as 80 percent or, in one particular syndrome, as high as 100 percent unless we intervene.
Wow, now Amie I'll just mention that I think about that a lot because my mother died at age 77. My father who happily lived to be 92, he would have colonoscopies, and they would not infrequently find precancerous polyps, and they'd snip them out, and his dad, my paternal grandfather, had been treated for rectal cancer. So I've thought about this. Is that that familial situation you were describing?
Exactly, exactly. What you're describing in your family is what we would call this common familial colon cancer, and if we look at every individual in the United States with colon cancer approximately 30 percent of them are going to have a close relative with colon cancer. So we do know that colon cancer has one of the strongest familial connections. So it is important to know about your family history and that would determine of course how often people go for colonoscopies.
Right, well let's take it further through. You mentioned though there's this other group where they may even have 100 percent risk or an 80 percent risk. Tell us about those folks and how they're identified in the first place.
Yes, good question. When we think about the hereditary colorectal cancers, they're typically divided into two main groups. One group is what we call the polyposis syndrome. That simply means individuals that have a propensity to develop lots and lots of colorectal polyps. The other group is what we would call nonpolyposis colon cancer, meaning cancer develops in an individual from a single polyp rather than lots and lots of polyps.
Now, if we go back to the polyposis group the most common syndrome is called familial adenomatous polyposis, and we abbreviate that FAP because it's quite a mouthful. It simply means a syndrome where individuals have a very high chance to develop lots and lot s of polyps — I mean hundreds to thousands of colorectal polyps — that are of the precancerous type, what we call adenomas. And this is a hereditary condition, therefore it can run in families.
With individuals who have FAP, we typically see hundreds to thousands of polyps start to develop as early as the teenage years and sometimes it can be a little bit later, developing in the forties or fifties as well. It can be variable, but these individuals have a striking clinical picture in that there are numerous colorectal adenomas. When somebody presents with lots of colon polyps, it of course raises the concern of this familial condition, and in fact if we look at the family history most of the time there will be other relatives with early colon cancers or who were known to have lots of polyps.
About one-third of the time this condition can just start new in that person, meaning that it was an error in the egg or sperm cell that became that individual, but their parents themselves were not affected with the condition. So we have a hereditary condition that's starting with this person with all of the polyps, and their descendents after them — their children, their grandchildren — are at risk for inheriting FAP.
OK, I've got a question for you right there.
So let's say someone like that comes to, is referred to UCSF whether they're the first person in the family or not, and then we're going to talk about testing in a minute, but you determine that this is their situation, and you know that 100 percent of the time or close to that it becomes cancer and that their offspring may well be at risk or if they have siblings and they weren't the first one, there could be others, then what conversation does the family have, and what action is taken?
Yes, good question. So the first thing we do is construct a detailed family tree or what we call a pedigree to try and get a feel for whether or not this appears to be a dominantly inherited trait or if it could be a trait that is recessively inherited. because one of these polyposis conditions actually can be recessively inherited and therefore looks like it skips generations. Once we've established that it looks like one of our known hereditary syndromes such as FAP, we offer the individual a genetic test. A genetic test is simply a blood test where the cells in the blood are analyzed to see if we can identify a specific gene mutation, most often in a gene called APC, which would explain their clinical picture of lots and lots of colorectal adenomas.
If we are able to identify that mutation, and I would say about 80 percent of the time we are in individuals with FAP, we can then offer genetic testing to their relatives — their siblings, their children — to help determine who is at risk for developing all these lots of polyps and who is off the hook. It allows us to tailor our screening guidelines. We don't need to be recommending additional colonoscopies at very young ages if an individual in a family tests negative for the mutation that is in their relative, but those individuals that test positive for this gene mutation will need to start colonoscopy quite young actually. Our recommendation is by the age of 12 to begin colonoscopy to be screening for the presence of these colorectal adenomas.
Once somebody develops too many colon adenomas for our gastroenterologist to remove by doing a colonoscopy, so usually an individual will have somewhere between 30 to 100, then they will need to go ahead and have a colectomy meaning removing the colon before cancer develops to in fact prevent colon cancer from happening, and that is unfortunately at this point the only way that we can prevent colorectal cancer in FAP.
Okay Amie, let's take the other side of the coin. So I understand there's another inherited higher risk for colon cancer where you don't have all these hundreds or thousands of polyps. What's that called, and what do you do then?
Yes, in general we call that category hereditary nonpolyposis colon cancer, and that is again where individuals would have a higher risk to develop colon cancer based upon having an inherited trait that was passed down from a parent. They have colon cancer that develops in a single polyp but not from hundreds or thousands of polyps. So the individual looks just like everybody else in the population in that there isn't anything in their colon that we can see that would make us suspicious that it's hereditary.
So the things that we look for in families that have nonpolyposis colon cancer are young ages of cancer diagnosis. The average age in hereditary nonpolyposis colon cancer is approximately 45 years, so we see young onset colon cancer. We also see other types of cancers in families with hereditary non polyposis, in particular what we call endometrial cancer or cancer of the lining of the uterus in women, and women have up to about a 60 percent chance to develop that type of cancer if in fact they do have Lynch syndrome, and men and women of course have an increased risk to develop colorectal cancer, men slightly higher than women, maybe approximately 80 percent in their lifetime. Women are a little bit lower, maybe about 60 percent in their lifetime for developing colorectal cancer.
So again we look closely at the family history to see if there are any features that suggest this hereditary condition. Some people call the condition "Lynch syndrome" and that is simply because hereditary nonpolyposis colorectal cancer can be a little bit of a misnomer. Here's a hereditary syndrome where there are other types of cancer that can occur, such as endometrial cancer in women, and it has been confusing for women for example to go to their doctor. They have endometrial cancer and they have a diagnosis of hereditary nonpolyposis colon cancer. Doctors have kind of looked at them sometimes and thought they were crazy, but in fact they were correct. They just didn't have colon cancer; they had endometrial cancer.
Right, right, and named for Dr. Lynch who's done research on this. Now again, do you have a genetic test so if someone comes in with that and you want to see is this really what's going on and what about other family members, the same as what we talked about with FAP?
It's a similar process. One of the interesting features of patients who have Lynch syndrome is that their tumors show a specific feature that we call microsatellite instability, and basically there are regions in our genes that are made up of repeated letters or repeated bases, and remember our genetic code is spelled out in A, C, G, and T. So these repeated regions in our genome are highly susceptible to acquiring mutations, either insertions or deletions, when an individual has Lynch syndrome. It's a basic pathology that occurs due to the type of gene mutations that they carry.
This feature, microsatellite instability, can be seen in their tumors. So our first step is usually to analyze the colorectal tumors or the endometrial tumors in the pathology laboratory to see if this feature that we call microsatellite instability is present. If it is present then we go ahead and offer genetic testing for one of the three genes that are currently commercially available. These genes that cause Lynch syndrome are a family of genes that are called mismatched repair genes, and it comprises approximately as many as six different genes, and at this point we know that four of these genes in fact can cause Lynch Syndrome when there is a mutation, but we can really only do gene testing for three of them clinically at the moment.
Okay Amie, so there we are. So one way or the other via pathology or the other tests you say this is what's going on here. Then you look at that with other family members and what do they do? So in one case, the FAP case, we said may get to the point where somebody needs their colon removed and now maybe deal with the colon cancer risk. Here we're talking about a constellation of cancers. Is it just a lot of screening and surveillance?
Yes. In general our recommendations in families that have Lynch syndrome include beginning colonoscopy starting at the age of 20 years, and they repeat that colonoscopy every one to two years for the rest of their life. We do know that the cancers that occur in the colon in individuals with Lynch syndrome grow at a much faster rate than they do in the general population. So the screening interval needs to be very short because if we wait three years that can be too long between there being nothing seen in the colon and a full blown cancer.
What about the other cancers though — endometrial, ovarian, etc?
Yes, so our recommendation for endometrial cancer and ovarian cancer are based on the best known screening tests that we currently have, and I will say that screening for gynecologic cancers is not particularly sensitive in identifying these cancers; however, there has been some evidence to suggest that doing what we call endometrial biopsy, this is where the lining of the uterus is biopsied in several different locations, can help to identify early cancer or even precancer in women with Lynch syndrome.
So our recommendation is starting at about the age of 25 to 30 years of age to begin having endometrial biopsies with a gynecologist who's experienced in this type of a procedure as well as having a transvaginal ultrasound to not only look at the ovaries but to look at the lining of the uterus and then we recommend a blood screen called CA125, which is a marker for ovarian cancer, and again these screening tests for ovarian cancer, such as the ultrasound and the CA125, have not been proven to be particularly helpful, but they're the best that we've got right now, so that's what we recommend.
Because our screening is not so good in Lynch syndrome or in general for those types of cancers, it is recommended that women who are completed with childbearing, they no longer plan to have any children or maybe they're already post menopausal, we would recommend that they remove the uterus and the ovaries to prevent cancer, and our center in collaboration with MD Anderson Cancer Center have published data to indicate that there's a 100 percent reduction in the risk for ovarian and endometrial cancer when women have these surgeries if they have Lynch syndrome.
That's what it's about — cancer prevention. We just have a minute or so left Amie. So obviously your center, the UCSF Cancer Risk Program, is very devoted to this and sounds like is helping lead the way. If someone has this concern — maybe they haven't been treated at UCSF — it sounds like a consultation with a genetic counselor such as yourself might either give them a plan or give them peace of mind.
Yes, we'd be more than happy to talk with anybody who has questions or concerns about their own personal diagnosis of cancer or a family history of cancer. They can reach us by calling (415) 885-7779. You can also find more information about our program online.
That's great information. I'll just mention here's another number for people. The overall physician referral service for UCSF is (888) 689-UCSF, or (888) 689-8273, and that can help connect you with the broad range of UCSF providers. Amie Blanco, genetic counselor at the UCSF Cancer Prevention Program, thank you for helping us understand prevention of hereditary colorectal cancer, diagnosis of it, helping people understand what they're dealing with. We appreciate your time today.
It was my pleasure.
This is what we do on Patient Power sponsored by UCSF, and it always bowls me over when the understanding is there to help us really make better decisions for ourselves and our family. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.
Recorded September 2008
Reviewed by health care specialists at UCSF Medical Center.
This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.
Cancer Genetics and Prevention Program at Mount Zion
1600 Divisadero St., Second Floor
San Francisco, CA 94143-1714
Phone: (415) 885-7779
Fax: (415) 885-3787
Center for Colorectal Surgery
2330 Post St., Suite 260
San Francisco, CA 94115-1799
Phone: (415) 885-3606
Fax: (415) 885-7678