Host
Heather Simonsen, MA
Public Affairs Senior Manager
Huntsman Cancer Institute
Director, Utah Population Database
Professor in the Departments of Medicine and Human Genetics at the University of Utah Spencer Fox Eccles School of Medicine
Professor and Division Chief of the Division of Genetic Epidemiology in the Department of Medicine
at Spencer Fox Eccles School of Medicine
The UPDB: Understanding Disease Prevention and Survival (00:50)
Heather Simonsen: You're listening to Delivering a Cancer-Free frontier podcast.
Assorted Voices: To create and provide better treatments. Today, we can bring these discoveries and the science-based medicine to people in need around the state, region and the world. I feel like the future is very bright, and I can't even imagine what cancer care is going to look like over the next 50 years. To continue that journey to eradicate cancer from the face of the earth.
Heather Simonsen: Hello and welcome to delivering a cancer free frontier. I'm your host, Heather Simonson, we're going to start today's episode with Dr Nicola Camp.
Nicola Camp: I go by Nicki.
Heather Simonsen: She's an investigator here at Huntsman Cancer Institute and a professor of internal medicine at the University of Utah.
Nicola Camp: I came to the university about 27 years ago from England. Still have my accent. You may hear it. I am a mathematician, statistician, and proud to be the director of the Utah population database, or UPDB.
Heather Simonsen: The Utah Population Database is housed here at Huntsman Cancer Institute. It's an incredible resource, something that quite literally has changed how the world approaches cancer research and prevention.
Nicola Camp: So, the Utah Population Database is, as you might notice from the name, population based. It's also longitudinal and a multi-source data resource. But let me break that down for you. So, population-based means that we try and represent the whole of Utah, the whole population. Longitudinal simply means data over time. So, we're able to look at people over time. That's important, because we want to look at survival. We want to look at people who don't get disease, so we compare people with or without that helps us look for risk factors. And multi-source just there's lots of sources of data that come to us.
Heather Simonsen: At its heart, the UPDB is a massive genealogy resource.
Nicola Camp: It is billions of records. So, it's generally partitioned into many databases that all communicate with each other. We have teams of data engineers. We have genealogy that goes back a century or more. In some cases, we have cancer data for 60 years. We have other health data for 30 years, and we use it to understand disease prevention and survival.
Heather Simonsen: Now, all this information is crucial to getting to the heart of why cancer happens.
Nicola Camp: The Huntsman Cancer Institute's goal is a world without cancer. And how do we get there? So, we have to understand cancer from its beginnings, and we need to figure out how we can educate people to reduce, to prevent, to help people be healthy if they get cancers. So UPDB has many strengths towards kind of these very important goals. So, prevention is who gets the disease, who doesn't? So, we're able to look at that. What are the risk factors? Some of them are inherited and genetic. So, we're able to do that with the genealogy. We can understand what runs in families, and if people happen to get cancer, we can study the best care strategies. What are the factors that help with survival and keeping people healthy?
Heather Simonsen: And it's the reason why more inherited cancer genes have been found here than anywhere else in the world.
Nicola Camp: It really is…it's unparalleled in the US, and there are very few resources like it in in the world. So, the reason why it's so impactful is we can ask and answer questions that others really just simply can't do.
Heather Simonsen: On today's episode, we're delving into the Utah population database, how it works, how it was founded, how it changed our understanding of genetics and cancer…and where it can take us in the future.
Four Visionaries (4:30)
Heather Simonsen: The story of what is now the Utah Population Database began in the 1960s and 1970s.
Nicola Camp: I actually think it's fair to say that it starts with an amazing community here in Utah, one that's really interested in genealogy and family.
Heather Simonsen: Nicki Camp also credits four visionaries. One was surgeon Charles Smart.
Nicola Camp: He understood the importance of understanding cancer surveillance.
Heather Simonsen: He started the Utah Cancer Registry. Utah was one of the first states to be a part of the National Cancer Registries across the country. Then there was Mark Skolnick.
Nicola Camp: I would call him a genetic epidemiologist today; the terms have changed over time. He really wanted to understand how diseases cancer ran in families. He really thought about this idea of pulling the genealogy and the cancer registry together.
Heather Simonsen: Roger Williams…
Nicola Camp: …who was a fabulous cardiologist in internal medicine here, but he understood that he could use what was in the hospital records with the genealogies.
Heather Simonsen: And Lee Bean.
Nicola Camp: He was a demographer who was very interested in, how does cancer change over time? How does it change with people's demographics? Does it influence longevity, fertility, all of those other things. So again, from a demographics perspective. And all four of those people really came together and really generated a lot of interest and excitement in ultimately what became the UPDB.
Lisa Cannon-Albright: So, we just called it the Utah Genealogy. And yeah, I came to Utah early enough that I actually physically saw it being built.
Heather Simonsen: This is Lisa Cannon-Albright.
Lisa Cannon-Albright: I would say, the definition of what I do…the title, I would say, is statistical geneticist.
Heather Simonsen: Lisa is also a researcher at Huntsman Cancer Institute and a professor in the Department of Internal Medicine in the Division of Epidemiology.
Lisa Cannon-Albright: So, I use genetic data, usually in the form of pedigrees—
Heather Simonsen: —which is basically a massive family tree.
Lisa Cannon-Albright: A pedigree that I study might be 12 generations deep, and it could easily have 30,000 individuals who all have that same founder 12 generations ago. It's a lot of people. Big families are so powerful for genetics, and you know, they're not studied as much as you might think, as valuable as they are, but that's just because data on extended, deep families is just not generally as available as it has been to me.
Heather Simonsen: She says she fell in love with statistics when she was in college.
Lisa Cannon-Albright: I really credit my mom, my parents, but really primarily my mom, with always telling me that math was the thing I needed to understand and do math. And I was like, oh my gosh, statistics, it's like a toolbox, and I can carry it to whatever set of data I want to and use it. Like this is really the door and the key. And what my mom was talking about.
Lisa Cannon-Albright: I was a statistician for an insurance company, and I just really prefer to forget all about that. I mean, it was the most boring. It was so awful. But, you know, I just thought, you gotta get a job and make a living.
Heather Simonsen: But then her sister in Utah sent her an article.
Lisa Cannon-Albright: About this guy in Utah who was building a computerized genealogy to study the genetics of cancer. I saw that, and I was like, wow, that is really pretty cool. Maybe I should go check that out.
Heather Simonsen: She came to Utah and started a master's in biostatistics.
Lisa Cannon-Albright: And a couple of my professors actually worked for this person that I had read about who was building the genealogy, Mark Skolnick —
Heather Simonsen: — who Nicki Camp cites as one of the visionaries behind the UPDB.
Lisa Cannon-Albright: So, I just went over one day and I said, I'm getting a master's, but you're doing what I want to do. And I mean, I still remember his office. He had this big old wooden desk. He had this, like, really ugly visitor's chair that was, like, red and sparkly. I mean, it was the 70s. And, I mean, I still remember he was telling me what he was going to do, and in my head, I was like, this is it. You found it. You found what you want to do. And this guy has the tools and the knowledge and the enthusiasm. And I never looked back like from that day. I was so lucky.
Finding the Genes that Cause Cancer (9:38)
Lisa Cannon-Albright: When I met Mark, that's what he said. We’re trying to find the genes that cause cancer. There weren't a lot of people even who believed that it was genes that caused cancer.
Nicola Camp: There were a lot of naysayers.
Heather Simonsen: This is Nicki Camp again.
Nicola Camp: Especially because cancer is actually quite common. And so, I think it was understood at the time that there were these very rare disorders that were so obvious, even to like, you know, the lay person, oh, gosh, look, the dad got it. Now the daughter has it. Oh, and now the granddaughter has it. And those are rare and very highly penetrant, meaning that if you get the gene, then you're almost certain to get the disease. So those types of things were kind of like, yes, we know those are genetic. But something as common as breast cancer? One in eight women get it, right? You know, much lower in men. But they were like, no, it's environment, it's viral, it's just random, right? These were the things that people were like…no, you can't. And really, there was, there was a cohort of people, which include Mark Skolnick here, who just were like, no, I really, truly believe this is genetic. And understanding that it kind of occurred more often in family members was the first clue. But of course, that doesn't have to be genetics. And so, it really took people who believed that that was the case. And this is in a lot of science, right? You can walk away from anything that you're doing, because it takes time, energy and a belief that you think you're seeing the pieces, and you think they fit together, that you keep going.
Heather Simonsen: A big step in the early 1980s was to link the cancer records to the genealogical data.
Lisa Cannon-Albright: Back in those days, we were very much creating our resource. That is, we had to identify the families we wanted to study, and it was very much focused on breast cancer. The computer was in the computer room. Distantly, I don't even think it was on the same floor they would be up typing the genealogy data into these terminals that was collecting it and doing the record linking on the fly and building this genealogy, which ended up 1.3 or 1.5 million people. I think it was about six generations deep.
Nicola Camp: What is genealogy? It's a massive, big family tree. So, imagine that in front of you. A cancer registry, so all the cancers that have been diagnosed or treated in Utah. Take all of those cancers and throw them on this family tree, and suddenly, in front of your eyes, you can see that it isn't just a random set of people in on this genealogy. There are clusters. There are these groups. People who are closer relatives have more cancer, and then there are other places where there are gaps and people don't have cancer. So, what does clustering mean? It means that close relatives who have cancer, other relatives have cancer. So, maybe it's genetic. So, we start with that, and then we say, okay, well, if we think it's genetic, how do we find the gene?
Lisa Cannon-Albright: With breast cancer, you know, I have to say those families were just like so dense with early onset, it was just very clear the families that we were studying for breast cancer were different.
Heather Simonsen: So once all this information was compiled, clinical coordinators asked families most affected by breast cancer if they'd like to participate in the study.
Lisa Cannon-Albright: In Utah, people are just happy to help. Oh, I'm in a family that has a lot of breast cancer, and you want to study me? Absolutely. Can I bring my sisters and their kids? You know, it's just, it was just amazing.
Nicola Camp: Shout out to the Utah population. The people who live here care about their families, right? They want to pay it forward, because finding genes takes decades. But we had people who were…participation rates here to be in these studies were through the roof compared to other places, because people wanted to be involved.
Lisa Cannon-Albright: And so, we got blood samples, and later we used those to extract DNA. Half of theirs came from mom and half of it came from dad. So, the idea was, we'll identify what they got from mom and what they got from dad and see if there are any genetic markers that travel through the pedigree, that travel with the disease. If you find them traveling together, you've just found the neighborhood of the breast cancer gene.
A Major Discovery: BRCA1 and BRCA2 (14:43)
Heather Simonsen: It took decades for all this incredible scientific labor to come to fruition. But when it did, it made a huge impact.
Lisa Cannon-Albright: The Utah families that we studied, this resource that we had built, this was the resource that was used to find the first breast cancer gene, BRC1, then BRCA2.
Heather Simonsen: BRCA1 and BRCA2 are inherited cancer genes, perhaps the most well-known cancer genes. People who inherit a mutated version of these genes are more likely to get both breast and ovarian cancer. According to the American Cancer Society, more than 60% of women who inherit a harmful variation of those genes will develop breast cancer in their lifetime. The complete story of how BRCA1 and BRCA2 were found is much more complicated. But the data in the UPDB that Mark Skolnick and coworkers were compiling in the 70s and 80s was the backbone of the discovery.
Lisa Cannon-Albright: You know, when things happen, you don't stop and celebrate the moment, because you don't actually realize it's the moment until much later. And so now I take a great deal of pride, because really, you know what our group contributed to is world changing, life changing… but at the time, it was just, you know, wow, we did it. Yeah, yeah, my husband, my kids, they're very proud. It's, it's very sweet.
Heather Simonsen: The discoveries of BRCA1 and BRCA2 genes were a game changer for researchers’ ability to understand cancer at its source and how we approach prevention. That is, how we can stop cancer from occurring in the first place. Director Nicki Camp says the BRCA genes were just the beginning for the Utah Population Database. But the resource continues to evolve and grow.
The UPDB: How it Works (17:01)
Nicola Camp: So, one thing we probably can't emphasize enough is the importance that a resource like UPDB had on genetic discovery in cancer. And UPDB and really that early work that Mark Skolnick and the others did really solidify this idea that, no, it runs in families. I mean, we've definitively, kind of made that discovery here. And, of course, that just kick started so many other questions. Okay, so if it's familial, which just means runs in family, is it genetic? Because, of course, there are lots of things we share, diet, we share environment. Is that familiarity, is it genetics? So, you know, the UPDB itself does not have DNA. We don't have a bio bank, but we helped design the studies, powerful studies that were able with, again, with the amazing participation of the community, to put us on the map as being the place that found breast cancer genes, ovarian cancer genes, prostate cancer genes, colorectal cancer genes, neurofibromatosis, melanoma. I mean, the list… more genes here than anywhere. And it literally is because of this kind of recipe that that we have in terms of amazing data, but also an amazing community that's invested in making a difference.
Heather Simonsen: Yeah, and you know, one thing that's really unique about Huntsman Cancer Institute is that more genes for inherited cancers were discovered here than anywhere else in the world. As you know, it's such an amazing resource and so unique and first of its kind. But how specifically do scientists use it in the lab for cancer research?
Nicola Camp: Okay, so we look at clustering, still, both cancers, multiple cancers, cancers and non-cancer phenotypes. Because, of course, cancer patients get other diseases. How does that occur? We look at cancer cohorts, so populations of people with cancer, cancer survivors. Therapies can damage parts of the body that then increase risk. So, understanding what those vulnerabilities are and how people can avoid and understand their vulnerabilities. I'll give you an example, which I think will probably resonate with lots of us. So, kids who get leukemia, they can get compromised lungs, and we have bad air days here in Utah, right? And we know that people who have asthma and others are…we get those reports on the radio, keep these kids who are vulnerable. Well, research here is showing that perhaps those children with leukemia should be part of those groups. So that was kind of like a first discovery of things like that. And you know, those are the types of things that can influence national guidelines to keep kids safe.
Heather Simonsen: Right. And like, back to the BRCA1 and 2 genes, if you know that runs in your family, you know your doctor can recommend more aggressive screening to make sure that you're still healthy, right?
Nicola Camp: Absolutely. So, there are guidelines that genetic counselors will use when they're advising people of their risk. And there are actually two main factors in that. The first factor has nothing to do with genetics. It's family history. It's like, who in your family had what cancer at what age, right? And we can do that just with what we have in the UPDB, right? Because that is, that's family history. The other piece is, if someone in your family already is known to have a mutation, a change in the BRCA1 or 2 or other gene that increases risk, that obviously is part of the equation too. So, we share half of our genes with our parents. So, if my mom was to have a BRCA1 mutation, I have a 50/50 chance of having it. So, if other people have had genetic testing that is important to understand. Who was it? How far away were they in terms of relationship? I share more with my parents and my siblings than I do with my cousins, for example. But also, that configuration, that pattern of which family members had which cancer, and that's what genetic counselors will work with. And both of those pieces we have contributed to. I can give you a statistic here, because I found a paper just recently. Just for BRCA1and 2, there are a quarter of a million people annually who get tested so they can understand their risk, and if necessary, you know, avoid getting cancers. And that's amazing thinking that that came from right here.
Heather Simonsen: Can you give us some some other examples? Or did you do you think you mentioned most of them? You mentioned breast cancer, colorectal cancer. Are there any other examples of breakthroughs? Or did you cover them all?
Nicola Camp: No, I would need a very long list to cover them all. So, the ones I'm mentioning are ones that were found, in some ways, long enough ago that they make it through all of the different steps to actually get to a clinic. There are other genes that have been found— hematological malignancies, brain cancers, various others that have happened that are just in that pipeline, right? Because it's a high bar to move from a research discovery through making sure that, you know, we want to do no harm. So, I think there's a…there are many I think that are probably still to come. There's also many that I think will take a little longer to find because of complexities. And that's kind of what we're chipping away at now in terms of genetics, is a lot of the early discoveries, I think, arguably, if we look back, are genes that, by themselves, with nothing else happening, give people a really high risk. But if you can imagine, there may be genes that really increase your risk, but only in a certain context, maybe only if you have a poor diet, or maybe if you don't get enough exercise, or maybe if you're exposed to some kind of exposure in your area. And that requires us to think of all those other non-genetic factors at the same time when we're doing the discovery. So now it becomes a much more complicated kind of discovery process. So, and that's so…you know, we've made a lot of discoveries. I think there's a lot still to come, and I think it's going to be new techniques and new methods using this amazing data that we have. For example, AI may actually, you know, be part of our next generation of discoveries.
Heather Simonsen: Right? Because the future is so bright in that regard. I mean, to have instant access and to be able to cross reference data with the use of AI so quickly, I would imagine there's so much potential there.
Nicola Camp: Yeah, I think there's a lot of potential. Like I was saying, that really is the strength of things. You know, computers can look at so many different things all at once that humans really can't. And when what you're looking for is that…you're looking for a pattern that then, as humans, we can see that pattern. And then we can start digging in, but it's given us a place to look. Just like way back when they suddenly realized there were clustering in families, that then gave the impetus to move to looking for genetics and how we designed a study. The same thing will happen. We'll find something. It will tell us how to design the specific studies that can then ask the more specific questions that will lead to the discovery. So, it won't take humans out of the equation, but it will help us know where to look.
Heather Simonsen: And how many researchers are using the database currently?
Nicola Camp: Oh, we remain very popular. So right now, I think there's about 250 different research groups that have permissions in place to be able to request data sets. And of course, each research group is several people, so it's thousands of researchers, even just here at the University of Utah, and many of those will have collaborators of experts elsewhere that come in and work together. We generally get about 100 requests a year from those people to put together new data sets, to ask new questions, and then we help them write and publish their work so it gets out there in the in the field, so it can make a difference and move along that conveyor belt from first discovery through to clinical impact. We also have what's called an idea meeting, and we do about one of those every week. So, these are new people who suddenly have found us for whatever reason, and we meet with them for an hour, and they talk about what they're interested in, and we talk about how we might be able to help them. So, an important point is that while we steward the data, we do not do the approvals to use the data. And in fact, in the 80s, the governor, through an executive order, put in place an additional ethical body at the university that works in our institutional review board, so an additional committee that reviews anybody who wants to access the data. So, we have that kind of division of the stewardship and the dispersal data to investigators and the ethical oversight and the access piece.
The Next Frontier: The Future of the UPDB (26:48)
Heather Simonsen: And what's the next frontier would you say? I mean, what's yet to be discovered?
Nicola Camp: Oh, goodness me. I mean, I think going back to that complexity we were talking about, I think being able to kind of deconstruct that complexity is going to be that's a huge piece that we need to do. I think the other thing that we haven't talked a lot about but is another huge strength of the Utah Population Database, is just how long it's been here. At the beginning, I told you it was a longitudinal database, right? And it is. And I think that area of, well…what was the risks that happened, you know, while you develop as a child, as an adolescent, how does that influence the risk to cancers, which mostly happen in later life? Because, obviously we need to know that, because that will guide how we, you know, how we nurture our children to avoid some of the things later on. And I think this idea of the breadth and thinking about that kind of lifelong ability that we have to really think about, you know, how do we keep our population healthy, from the very young to the very old.
Heather Simonsen: I think that's so important. And especially, you know, it's like treating the whole patient throughout their lives, and not only the patient, but the family. And I mean it's a big part of our mission here at Huntsman Cancer Institute. So, everything that you're saying really resonates. And people who may be listening to this might wonder, how does this benefit me? What would you say to people who are listening like, how does all this amazing science…like how can it potentially benefit the average Utahn?
Nicola Camp: So, I think one of the things I would point out is because what we can do here are population-based studies. The discoveries made are relevant to our population. It's important to understand that, you know, research is one of the very first steps. That research and discovery is the very first step of a long journey until it actually really impacts. Is it going to… is a discovery made today going to help somebody tomorrow? No, it isn't. Is it going to help them in 10 years? Maybe. Is it going to help their kids? Probably. Right? So, there's a long investment here, but the importance is that it's here and it's relevant to our population. And largely it's also relevant to the world. I mean, we've shown that with the genes that were found here, they're not just Utah centric, but I think it's important to know that, first and foremost, the things that we're finding are relevant to the people.
Heather Simonsen: Thank you to Dr. Nicki Camp and Dr. Lisa Cannon-Albright for joining us today. Information in the UPDB is protected using the highest industry standards, including protections for IT security and patient privacy. Access to UPDB data is highly restricted and involves rigorous reviews of research teams and their intent, ethics and usage plan. Funds from the federal government and private donors, including Huntsman Cancer Foundation, have been crucial for the discoveries made with the UPDB. To our dedicated listeners, we're so thankful for your support. For additional resources, be sure to check out our show notes, and if you want to stay connected with us and be the first to know about upcoming episodes, subscribe on your favorite podcast platform. Please log onto Apple Podcasts and leave us a five-star review. This helps other people like you find this podcast. If you have questions, comments, suggestions for future episodes or a personal story you'd like to share, please visit our website, Huntsman cancer.org. Theme music composed by Mix at Six Studio. Additional music from Artlist. I'm your host, Heather Simonsen. A special thanks to Huntsman Cancer Institute's Communications and Public Affairs team.