Childhood cancer
Fighting a parent’s worst nightmare
This time we had the opportunity to converse with the Principal Investigator of the 10,000 Families Study, Logan Spector, Ph.D. As Principal Investigator, Dr. Spector is the leader of a team of researchers that guide all activities related to this Minnesota family-based study.
Logan is Director of the Division of Pediatric Epidemiology and Clinical Research and a Professor in the Department of Pediatrics at the University of Minnesota Medical School.
This is what we asked and what Logan told us:
Your biography says that you have a doctoral degree in Epidemiology and your research work is focused on childhood cancer. Could you help us understand this a little better?
For instance, what is Epidemiology?
A simple way to describe this concept is to say that Epidemiology is the study of who, when, where, why, and how people get the disease. Another way to describe it is to say that it is the study of disease in populations, as opposed to what is studied under a microscope or in the lab. Basically, epidemiologists study why people get diseases on the population level.
How did you decide to study Epidemiology?
I was a biology major in college. I always knew that I wanted to be a scientist since I was in middle school. But studying biology I realized that I didn’t like the lab as much. So I looked for a branch of science that would let me do research but wouldn’t tie me to a bench. Eventually, I realized that this branch had a name - Epidemiology!
How did you decide to focus your Epidemiology research on childhood cancers?
When I went to Emory University for my Ph.D., I wanted to study infectious diseases. In fact, I spent about one and a half years on a dissertation looking at tuberculosis in a rural Florida community and whether it would be transmitted in schools. Then when that didn’t work I started looking for other dissertation topics. Someone connected me with the vaccine safety branch of the Centers for Disease Control and Prevention (CDC), which is close to Emory University. They wanted someone to look at regular vaccines and whether they could modify the risk of pediatric leukemia, starting with Acute Lymphoblastic Leukemia (ALL). This grew out of an abundance of caution by CDC when the incorrect assumption that vaccines cause autism first appeared, so the CDC decided to look at the association between vaccines and other childhood diseases.
I decided that I was really interested in pediatric cancers because kids shouldn’t be getting cancer and there was not a lot known about what causes them --so it seemed like there was a lot of room for me to make a mark on the field.
When I was doing my research I realized that there were a lot of papers coming out from the University of Minnesota, from the unit I now run, the Division of Pediatric Epidemiology and Clinical Research. The reason they were able to concentrate on this specialized field was because of the strong philanthropy base here in Minnesota, the Children's Cancer Research Fund that is still funding part of my research. When I started learning about pediatric cancer I realized that it is a very fascinating field on top of helping a very vulnerable population, which also makes me happy.
Why is it important to study rare childhood cancers?
They are rare especially compared to adult cancers, but pediatric cancer is the leading cause of death due to disease in young children. It pales in comparison to motor vehicle accidents, which are the leading cause of death, but in terms of diseases, cancer is number one. There are about 400,000 kids a year worldwide who develop cancer, so it is not an insignificant problem. If we mean to do well by the world’s children, we have to study the diseases that affect them; otherwise, we would be leaving these kids with life-threatening illnesses without any care.
Could you share with us what you are learning about the links between genetics, environment, and lifestyle/behavior in your cancer research?
I’ve been studying the causes of pediatric cancer for over 20 years. When I got into the field, I thought children are uniquely vulnerable to environmental toxins and that would be the answer. Although they are vulnerable, we don’t have a lot of good examples (apart from radiation) of the environmental causes of childhood cancer. We do have some very strong evidence for environmental causes like air pollution. Environmental impact does happen, but not as strong as people would assume. During my career, we have had the revolution in genomics, and it turns out that a small portion of kids had mutations and what I call “bad news” genes, but in some cancers like bone cancer, up to a third of the patients have mutations and bad news genes. However, to our great surprise common variation that any human might have is more associated with pediatric cancer than adult cancer.
There is also a role for sheer chance, unexpected occurrence. As far as the interaction between gene and environment, we don’t have enough data in pediatric cancers yet, in part because it has to be examined in large sample sizes. In some cases, the sample estimate exceeds the number of kids that have developed cancer in the last 100 years. We don’t have any good examples yet but may be able to find some in the near future.
For us to understand better, Could you share with us about one study in particular in this area and what you’ve learned?
I conducted the largest study to-date looking at conception In Vitro Fertilization (IVF) and childhood cancer. This was an important study to do for a couple of reasons: #1, until the late 80s-early 90s, in vitro conception was not possible, so there were no humans who had spent their earliest moments in a laboratory in a petri dish (circular, transparent lab dish). Since then, people have wanted to study different outcomes in those kids. Pediatric cancer I already said is rare, and IVF is only about 1.5% of births. So our solution was to start a very large cohort study, similar to the 10,000 Families Study: take a group of people that could be at risk, and we follow over time to see who develops the disease. We linked records of 250,000 kids who were conceived by IVF to their birth records and cancer registries, and we demonstrated that for the most part there was no increase in risk of cancer among those who were conceived in vitro compared to natural conception, but there was a doubling of risk for rare liver cancer that I study. This was important because there was a totally new exposure in the population that needed to be understood. I also like to think that we reassured parents that had a child by IVF or were considering having a child by IVF that, at least in regards to cancer, IVF is largely safe.
Could you tell us about what you are working on that is especially new and potentially groundbreaking?
I have a new grant starting in which we will conduct what I think of as a natural history study about in utero development of leukemia. This could lead to screening for pre-leukemia and potentially early detection and even someday prevention entirely of leukemia. We are working with the Children’s Oncology Group and identified about 300 kids that stored cord blood at birth and who have leukemia. Other researchers have done this using samples where they backtrack leukemia, meaning they look at the tumor genetics and then look to see if there are signs of it in the cord blood. We are going to do it at a much larger scale and much finer detail. We are going to pinpoint the cell type where these mutations occur and thrive, and we are going to figure out which occur in utero and which happen after birth. Potentially it means that we could isolate a group of kids who are at the highest risk of leukemia, follow them over time, and figure out what it is that makes it progress from pre-leukemia to overt leukemia. After that, we can think about prevention. That is a very exciting line of research.
In addition to this great study that you just told us about, what else gives you hope when it comes to childhood cancer?
There’s a 10-15-year $50 Million-a-year appropriation that Congress made for childhood cancer research. It’s not so much the amount of money that gives me hope but the fact that under the last administration Congress managed to pass this bill in a bipartisan fashion. Even in divided times, people can come together to address childhood cancer. That gives me hope!
Is there exciting news in your area of research you would like to share with our audience?
There’s a rare liver cancer that my research group happens to specialize in studying: hepatoblastoma. However it’s becoming less rare. In fact, it is the childhood cancer with the fastest rising incidence, as we documented two years ago. We’re closing in on the world's first Genome-Wide Association Studies (GWAS) of this disease. The GWAS might have revealed the reason for the rising rate. It cannot be population genetics because population genetics don’t change that fast. The variant that we found is related to type 1 diabetes and obesity. What these data are telling us is that this cancer is related to maternal obesity, which is rising around the world. So, we may have discovered why this cancer is becoming more common globally.
Tell us about your work with the 10,000 Families Study, what is your job with the study?
I am the Principal Investigator; although we have a group leadership model, someone has to declare that the buck stops here, so it stops with me. Ultimately I have responsibility for making final decisions, but truly we have a consensus-based group leadership model.
How does 10KFS contribute to your own research goals?
My field is pediatric cancer, and certainly, I don’t think 10KFS could be a vehicle for studying pediatric cancer as an outcome. However, we know pediatric cancer starts in utero, and potentially the mother’s behavior and exposure during pregnancy and the father’s behavior and exposure prior to conception can affect the risk of pediatric cancer. We are also discovering there are early-life factors related to late-life cancer. So my hope is that by studying families we can get at developmental origins of both cancer and non-cancer diseases. I’m very interested in disease initiation in utero, not just pediatric cancers.
Where do you see 10KFS’ greatest potential as a study?
I point to the Framingham Heart Study, which started in a small town in Massachusetts and initially was just going to research heart disease for a couple of years. The researchers ended up forming such a great relationship with the town that they followed people's health over decades, so without setting-out to, they created this incredible resource that grew over time. Unlike Framingham, I like to think that we are starting out creating this resource intentionally, and we are picking a medium-size state: Minnesota.
Let's talk about another of your projects
You are one of the co-founders of the Driven to Discover (D2D) project at the Minnesota State Fair. Can you share information about what D2D is, and how and why you started it?
It is a space for University of Minnesota researchers to make contact with the public at the State Fair, either to do studies on-the-spot or to locate people to do more extensive studies at the University. I arrived in Minnesota in early August of 2002, and a family friend said, “Hey, you’ve got to go to the State Fair,” and when I got there I said “Hey, there are a lot of people here,” and since I study people, I thought it would be a great place to do some research. I kept that in the back of my mind, and 10 or 11 years ago we started the Gopher Kids Study where we enrolled nearly 600 kids in the space of 6 hours at the Fair. That was a great experience and showed us that people would participate, but we needed our own space and we couldn’t justify buying space just for our study, so we opened it up to the entire University. We started in a shack built in 1953, not a very nice space, and still, people came and participated. Eventually, we convinced the University to invest in a new space: which is well designed, big, airy, open, and most importantly it has a roof. That is what D2D is, just space for University researchers to be out there with the public.
What value have you seen come out of D2D?
We have had dozens of papers come out of State Fair studies. We have had numerous grant applications and quite a few Ph.D. students who have done a portion of their dissertation at D2D. Other than last year, when the State Fair was canceled for the first time since 1946 due to COVID-19, we have been very full with faculty who want to be there; many come year after year!
Other than 2020, the 10,000 Families Study has been at D2D every year since it launched in 2017, inviting people to join the study. Now we know the State Fair will be back for a pretty normal 12-day run in 2021 from Aug 26 to Sept 6, can you tell us: What will 10KFS be doing there this year?
We’re doing a combination. As always, we are going to be talking to passersby about the study, which we love to introduce people to. At the same time, 10KFS is a commitment and it’s tough to introduce people to a big study and get their commitment all at once. So ahead of the Fair we are also going to invite people to join the study, and for a limited number of people, as many as we can afford, we are going to offer a free admission ticket. If they go through signing up for the study, doing their health questionnaire, and completing their consent and HIPAA forms, we will send them an electronic ticket, so they can come to see us at the Fair, any day between 9 AM and 2 PM. All we ask for is a blood sample from their finger. The idea is to attract as many people as we can this way. The Fair is very popular, and there is a lot of publicity, so we hope to ride on the Fair’s coat-tails.
For more information about this time-limited promotion for new Study participants, please contact 10KFS at [email protected].
How can people get involved in the 10,000 Families Study, and why should they?
The reasons they should can be personal, but I hope at-base most people want to help others, and by letting themselves be examined and followed for their health over time, that will help us understand the determinants of health and disease. The other reason people might participate is that the info we collect is medical-grade, and we will return their results to people. We also hope eventually to look at genetics and have discussed returning that information to people, though we are not there yet.
How was your research affected by the cancellation of the State Fair last year?
For a while the University was stopping anything that involved working on campus or seeing people, and only recently is it really opening up. It made it really difficult to do anything that required face-to-face contact. Last year we missed the opportunity of talking with the public, but this year we plan to make up for it.
If people attend the State Fair, why should they visit the D2D building?
Well, you actually get to meet the researchers, and they are very happy to explain the science. You will have a first look at how a small portion of science is done.
Do you have any last things you want our audience to know?
We don’t want to be seen as stiffs in white coats. We are researchers, but we are your friends and neighbors. We want to have a genuine relationship with our participants.
For more conversations about health watch our Facebook Live June 2020 with Logan:
What is worse, grandma's cake recipe or her genes?
