Research on Cancer!
What to know and how to help!
Our 10,000 Families researchers provide expertise in different areas of research. In our last newsletter we featured two 10KFS researchers who are involved in COVID-19 research. This time we are excited to introduce our researcher Heather Nelson, PhD, MPH.
Heather is a Professor in the University of Minnesota School of Public Health’s Division of Epidemiology and Community Health and Co-Leader of the Screening, Prevention, Etiology, & Cancer Survivorship (SPECS) Program in the University’s Masonic Cancer Center.
Here is Heather’s story and and her contributions to science in cancer, genetics, and immunity:
How did you get started in cancer biology, and why is it an important field?
A long time ago, when I was a graduate student, I did my training in very basic cancer biology, and we were studying what happens when genes become mutated in tumors. So then I started asking questions about how that happens in people: okay we understand how it works in an experiment in a lab, but is it the same in people? We took what we learned in experiments and then used epidemiology--the study of populations. There were many of us starting to think that way and it was the beginning of a new field called molecular epidemiology, which was combining laboratory science and population science. It’s very mainstream now, but back then it wasn’t.
I think that for everyone doing cancer research, many of whom come from different disciplines, understanding the fundamentals of cancer biology helps us ask smart questions.
Your main research focus now is how immunity intersects with cancer. Can you tell us about that and how you decided to study that?
We are all very different in our immune function, and some of that is about genetics, and some of it is about the environment we live in. Around 5 years ago my mother got breast cancer. I had not really experienced cancer at a personal level until then. She got really sick and ended up in the hospital because she was so sick from chemotherapy. Then I started thinking “what is going on here?” It seemed like it was more than just the chemotherapy, and I started thinking a lot about viruses, and that’s where most of my research is now. She came out of it okay, but it just really changed how I was thinking about cancer.
Not everyone who gets chemotherapy gets sick the same way; some people get very sick, and some people tolerate it better. Maybe it has to do with their health before they get cancer, maybe it has to do with viruses we live with that come back out. When you have cancer you have a new experience with these viruses because you’re immune-suppressed, meaning that your ability to fight infections and other diseases is reduced. So, I have asked myself: how does that matter for when you’re having treatment? and going forward: does it matter in your long-term outcomes and how you feel? These are things we’re interested in finding out.
Let’s back up a bit. Could you tell us what immune function is and why it matters? We can think about our immune system as if it were a community, and there are different roles within the community. There are some cell types that are the first responders--they show-up to the emergency. There are other types that are the support team. There are other types that are the story keepers that have the long-term memory of what has happened. How we experience life shapes our immune system community, and that impacts how we respond to new things. We’re learning that viruses are really important in shaping our immune system community. So in addition to thinking about how viruses might matter once we have cancer, I’m also interested in how viruses matter before we get cancer because if our immune systems are weak we are prone to cancer.
We’re all still thinking about COVID-19, can you tell us how immune function connects to COVID-19?
Sure. Let’s take someone with diabetes: their immune community will have a certain look shaped by having diabetes; there’s inflammation and other things which impacts the cell types we talked about before. Then there’s a new threat like COVID-19, and how that person’s immune community looks will matter for how well it responds to the new threat. That might be one of the reasons why people with certain pre-existing conditions are doing poorly with COVID-19.
On the other hand, say I don’t have preexisting conditions, but I encounter COVID-19. My COVID-19 infection then will shape what my immune community looks like, so I will have some long-term cells that remember COVID-19. Everybody responds a little differently to the virus, which could leave a stamp on you going forward. That stamp might shape what happens with cancer in the future, for better or for worse, and we won’t know that for awhile.
This conversation is very intriguing! Could you now tell us about a study you are working on in the area of immune function and what you’ve learned?
Back to thinking about viruses and cancer: At the time someone is diagnosed, they usually have a lot of inflammation related to their tumor, and they’re typically not well, which makes viruses that are usually quiet come back. Then when that person gets treatment, their immune system is suppressed and viruses can again come back. We decided to look at this in people with head and neck cancer and a common herpes virus (cytomegalovirus); over half of us have it by the time we’re adults. It’s typically not a big deal, but we wanted to know: when people have cancer, does it become active again and become a big deal? We can think about it like chickenpox (which is actually a herpes virus), you have it as a kid, and then it goes into hiding and later comes back as shingles. We wanted to ask something similar, whether this other herpes virus comes back out of hiding when people have cancer.
In about 30% of the patients in our study, the virus was reproducing when they were diagnosed, and nobody knew. A couple months into therapy, about 60% of the patients had this virus come out--so our hunch about the virus just hiding was right. The next step is to see if managing the virus makes people feel better--and if that matters for their cancer outcomes.
Now let’s talk about genetics. How do genetics and environment interact with each other?
There are different ways of thinking about it. Some genetic differences matter without environment; there are large genetic differences that are sort of deterministic for whether you get cancer or not. There is new research looking at the smaller differences between us, and when you add these small differences all together that means risk--called polygenic risk score. The other way of thinking about it is there are some genetic differences between us that don’t matter at all until you’re exposed to something environmental. Let’s take the example of sun exposure: We have genes that determine how much red pigment and how much black pigment you have. Those differences don’t mean a lot for skin cancer risk unless you add in the sun component: the more red pigment you have, the more likely you are to develop skin cancer.
Oh, so how about behavior and lifestyle? You can’t change your genetics, so we should think about where we can make changes that have an impact: you can modify risk. There’s a lot of research happening around genetics and personalized screening. For example, if I know that I have a much higher risk of cardiovascular disease or cancer, that should make me want to change my day-to-day habits, but it also should make me want to seek more preventive healthcare. For instance, I could choose to get screened for a disease more often.
From your point of view, what could be beneficial, or risky, about genetics research? Genetics can be empowering for you to have your healthiest life. People have chosen to learn on their own with companies such as 23 and Me. There are things you can find out, like what drugs you might not be able to tolerate very well.
We should think about genetic research as both personal empowerment and community empowerment. But we also have to acknowledge that some communities have been exploited by research, and genetic research in particular can be exploitative, and we must make every effort to make sure that doesn’t happen again. On the other hand, some communities have not been represented in research, which has also led to disparities because what we have learned about white urban communities may not apply well to other communities. We need to work to ensure that BIPOC communities (Black, Indigenous, People of Color), people living with disabilities, and people in rural areas can participate so they can benefit as well.
Can you tell us how all these factors--genetics, environmental exposures, behavior, and immune function--work together?
We have to think of them as a system, so none of them are in isolation and none is more important than the other. That’s why we have to work in teams. Some people will come to the research with interest or expertise in environment or immunity or genetics, and when we bring their expertise together, we can ask better questions about health and get better answers. We have these exposures in our environment that probably impact our immune function. One of the important jobs of the immune system is to scan and see viruses or bacteria or pre-cancer cells and remove them, so anything that disturbs that balance can make us susceptible to COVID-19 or cancer. It could be something in the environment, it could be our genetic make-up, it could be the viruses we’ve been exposed to in the past. There’s constant interaction between environment shaping immune function and events which further shape our immune function.
How do these things connect to the 10,000 Families Study? This is one of the ways 10KFS could be really powerful. If we start at childhood and we’re regularly measuring what you are exposed to, both in the environment and viruses, we can learn about how your immune system looks. If we do this over and over, we will understand what that means for health and disease.
