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Cancer has touched many of our lives. But what causes it? And how do treatments work? National Cancer Research Month in May gives us an opportunity to see how learning about the disease improves our chances to conquer it.
As cells grow and divide in our many tissues and organs, they copy all their DNA, the instructions that tell our bodies how to work. But their copying is not perfect. As time goes on, our DNA collects little changes called variants. If a cell collects certain variants—or a lot of them—it can grow out of control and become cancer.
Variants differ in different types of cancer. Some variants that increase our risk for cancer are inherited from our parents. These variants are already in our DNA when we are born.
To understand how variants cause cancer, first we need to know how our cells work. The cells in our tissues and organs are like a marching band. They march in line, form the right patterns, and follow rules to produce a perfectly orchestrated corps.
To achieve this choreographed routine, cells keep close control on how often they reproduce. When it’s time for a child’s legs to grow longer, for example, bones and muscle cells grow and then divide to make more of themselves. Cells control how fast they reproduce too. Some tissues, such as hair, grow and divide fast. Others, like our brain, grow very slowly.
When the Band Marches On and On and On
The copies of DNA in new cells need to be accurate. Sometimes things in our environment, like UV light or cigarette smoke, can damage DNA. Our cells have a way to check the quality of the DNA. They then fix errors or kill cells that have gone bad.
But the fix-it process isn’t perfect. Variants can get through. The older we get, or the more our cells reproduce, the more such variants can build up.
With enough trouble-causing variants, the perfectly orchestrated marching band wanders out of sync. The drummer might be slightly ahead of the beat. With cancer, the cells start growing out of control. They ignore the band leader’s baton. Eventually, the cancer cells take over healthy tissue and organs.
A common treatment for cancer, chemotherapy, takes advantage of the fast, unchecked growth of cancer cells. The drugs target cells when they try to divide, so they will kill more fast-growing cells, like cancer cells. But other fast-growing healthy cells, like hair, can also die. That’s why some people lose their hair during chemotherapy treatment.
Cancer Research Can Lead to Better Treatment
Years of research have helped scientists get better at finding variants in the DNA of cancer cells. And they can develop drugs that take aim at cells carrying those variants. This progress has helped increase the number of treatments we can use against cancer.
Some drugs go after particular variants with the help of the immune system. The immune system protects us from infectious agents like viruses by making antibodies against them. Researchers aim antibody-based drugs against variants. Some of these drugs will cause cancer cells to self-destruct. Others will call in immune system cells that are part of the body’s quality control system. Such drugs help the immune cells wipe out the bad cells. (Extra curious? The generic names of these kinds of drugs end in “-mab” for “monoclonal antibody,” but not all “-mab” drugs are for cancer.)
You may have heard that some COVID-19 vaccines are based on mRNA. COVID vaccine researchers based their designs on a developmental cancer vaccine. The idea behind mRNA vaccines for cancer is to rally the immune system to fight the out-of-control cells. The COVID-19 vaccines helped researchers learn more about this kind of technology.
Other research angles look for what’s common between different cancers. Often, researchers focus on a particular type of cancer. They then test different potential drugs on the same cancer in a lot of people. But sometimes the same variants show up in different cancers. In that case, maybe a drug originally developed for lung cancer will work to treat pancreatic cancer.
For example, a variant called the NRG1 fusion is most often found in lung cancers. But a 47-year-old man also had the NRG1 fusion variant in his pancreatic cancer. That allowed the man to enroll in a study that was testing a drug to fight cancers caused by the NRG1 fusion variant. This drug uses an antibody to find cells with the NRG1 fusion variant and wipes them out. Typical treatments had not worked for him. But early results from the study showed his cancer improving.
All of Us researchers are looking for answers to some important questions about cancer. Among other topics, they’re using All of Us data to explore access to health care for cancer survivors. A recent study looked at how people follow up with cancer care. The researchers found that up to 10% of All of Us participants who had cancer didn’t get treatment or follow-up care because they couldn’t afford it. Studies like this are possible because participants like you have been generous with your health, lifestyle, and other data.
If you’re interested in learning about other types of projects that researchers are doing with All of Us data, whether related to cancer or not, check out the Research Hub’s project list.
More than 491,000 participants who have completed the consent process.
More than 337,000 participants fully enrolled.*
More than 1,480 research projects are using All of Us data.
*Fully enrolled participants are those who have shared their health information with All of Us, including giving blood and urine or saliva samples.
All of Us participants are helping to build one of the largest and most diverse health research databases. And All of Us wants to make sure that health, lifestyle, and DNA data get used widely. A group of Researcher Ambassadors are going to help with that.
The Researcher Ambassadors are scientists who are already using the All of Us database. They don’t work for All of Us or for NIH. They help spread the word about the program to other researchers.
All of Us selected researchers who were especially excited about the program for the job. The Researcher Ambassador Network is currently made up of half a dozen scientists. We’d like to introduce you to Ky’Era Actkins, Ph.D., and Josh Matacotta, Psy.D., M.A., two of those scientists.
Meet Ky’Era Actkins, Ph.D.
Dr. Actkins is a visiting postdoctoral researcher at Vanderbilt University Medical Center in Nashville, Tennessee. She sees her ambassador role as a bridge. She wants to connect skilled researchers with ways to get the most out of the All of Us database. In this new role, Dr. Actkins is eager to learn more about the ins and outs of the program.
“I’m really excited about learning more about what’s to come and getting information to other people. Because the program has helped my research a lot,” says Dr. Actkins. “It’s really exciting to see what other ideas are out there.”
Dr. Actkins dug into the All of Us database to study polycystic ovary syndrome, or PCOS. PCOS is a hormonal disorder. Infertility is a common outcome of PCOS. People with PCOS are also more likely to develop type 2 diabetes and high blood pressure.
Dr. Actkins hopes to find clues about what causes PCOS. She says doctors also need better ways to diagnose the syndrome. The symptoms are so varied that large groups are needed for research.
“It can actually be very difficult to find a large number of women to study PCOS,” says Dr. Actkins. The program’s large database is one of the many advantages she sees in All of Us.
Meet Josh Matacotta, Psy.D., M.A.
Dr. Matacotta is a researcher who teaches health sciences students at Western University of Health Sciences in Pomona, California. Dr. Matacotta sees his work with health sciences students as part of his outreach. He encourages them to use All of Us to explore scientific ideas. It’s a great resource for students who want to perform research but are very busy seeing patients in the clinic, he says.
“I have told my students how wonderful it is that the All of Us dataset exists,” Dr. Matacotta says. “It lets students start projects earlier and wrap them up faster. The data has been collected. It’s well organized. It’s curated extensively before it gets to the researcher.”
Dr. Matacotta studies people with HIV infections and mental health conditions. Current treatments can keep HIV in check and prevent spread. Dr. Matacotta wants to know whether people with HIV still experience stigma the way they did in the past. He uses All of Us electronic health records and survey data to explore a connection between stigma and depression.
Dr. Matacotta applauds how All of Us sees participants as partners. “Participants aren’t passive volunteers. They’re playing a key role,” he says. “And I think what’s critical to the program’s success is that we’re all collaborating.”
Collaborating with hundreds of thousands of participants might seem hard to do, but researchers like Dr. Actkins and Dr. Matacotta know it makes All of Us special. So, they spread the news about the program, hoping everyone will want to be a part of it.
If you are an All of Us participant, you may have given us blood or saliva samples. Have you ever wondered how researchers can use the DNA from those samples to learn more about health? As of mid-March, All of Us researchers may be using your samples to do just that. Researchers can now perform studies with nearly 100,000 participant genomes.
A genome is a person’s complete set of DNA. Our genome holds our genes and other DNA that make us who we are. To make discoveries, many researchers are using that DNA data to perform studies called genome-wide association studies (GWAS).
What is a GWAS?
A GWAS (pronounced “jee-woss”) is a type of study that helps researchers find links between our genes and our risk for certain diseases. These studies look at changes, also called variations, in thousands of genes across the genome.
Think of yourself as a cake and your genome as a cake recipe. Your genes are all the ingredients that come together to make the cake. In this example, gene variants are differences in the ingredients from the original recipe. As bakers know, sometimes when you change the ingredients, something may go wrong with your cake. Maybe it’s too crumbly or too sweet. Similarly, some variants in genes can raise your risk of having certain medical problems.
However, sometimes when you change ingredients, your cake tastes even better than the original. Genetic variants can do the same. Some variants can help protect you from disease.
Another thing can happen, too. If you change the recipe ever so slightly, the cake can taste exactly the same. Your genes can do this as well. Some of your genes may have variants that never lead to noticeable changes in your health. Researchers can use GWAS to find out which variants might raise a person’s risk of developing diseases or other health problems, and which ones won’t.
To use GWAS to learn about disease, the first step is to compare gene variants in two groups of people. One group has a disease and one group doesn’t. If a genetic variant occurs more often in the group that has the disease, it could mean the variant plays a role in causing that disease. But it’s not always that easy.
Sometimes, the variants aren’t the direct cause of the disease. Imagine that scientists find a change in a gene that occurs more often in a group of people with lung cancer. It could be that the variant makes cancer more likely to form in the lungs. Or the variant could be linked to addiction, making someone more likely to smoke cigarettes. This too could make a person more likely to have lung cancer. Because there are so many possibilities, GWAS serve as a guide, often creating more scientific questions for researchers to explore.
Scientists who sign up to work with All of Us data can use computer programming tools to analyze the thousands of genomes in our database. Because we remove names and other identifying information from the data to protect participant privacy, the researchers will not know whose genomes they are studying. But they will know one thing for certain: the genomes they are studying reflect the diversity of the United States.
Why does diversity of GWAS participants matter?
Scientists performed the first GWAS in 2005. Since then, fewer than 5% of GWAS participants around the world have come from non-European populations. That means right now, most findings from GWAS only apply to people of European descent. All of Us is working hard to change that.
The assortment of genomes in our database are diverse. Nearly 50% come from participants who belong to racial or ethnic minority groups. And more than 80% come from members of groups that have been left out of medical research in the past. That includes members of the LGBTQ+ community, people with disabilities, and people who live in rural areas. Data from these groups gives scientists the opportunity to make new discoveries. They can look for changes in genes that are linked to diseases in non-European populations. They also can learn more about how our unique circumstances influence our health.
Findings from GWAS that use the All of Us database could open the door to new discoveries. That could help lead to better, more personalized health care for everyone. In the future, information about differences in our genes may also help doctors prescribe medicine that works best for each person.
To Our Participants: Thank You!
We want to thank our participant partners for all you have contributed to health research with us so far. As we continue working with researchers, the data you have provided may be used to answer real questions about health conditions that affect thousands or millions of people. We are so grateful that you continue to be a part of the All of Us Research Program. And we can’t wait to continue making discoveries with you.
Voices of All of Us: Billy Caceres
Billy A. Caceres, Ph.D., R.N, was one of the earliest researchers to begin using genomic data within All of Us’ Controlled Tier. His work using All of Us data will provide insights into health disparities among participants who are sexual and gender minorities. Learn more about his research using All of Us data and how Dr. Caceres’ background influences his work in the latest Voices of All of Us feature.
The All of Us Journey Exhibit
All of Us hits the road! The All of Us Journey bus helps visitors from different communities learn about precision medicine research. Visitors can see the power of participation in health research firsthand. You can even sign up to be an All of Us participant, if you choose to. The bus is currently in Knoxville, Tennessee. Find out whether the All of Us Journey is coming to a city near you!
All of Us Celebrates Our Fourth Anniversary
On May 6, we celebrated All of Us’ fourth anniversary. We have accomplished so much over these last 4 years. We’ve built one of the most diverse genomics databases. More than 2,000 researchers have registered to use our data. So far, 116,627 participants have received an invite to get their genetic ancestry and trait results. And nearly 500,000 people have begun their participation journey with All of Us. We wouldn’t be celebrating all of these accomplishments without you. Thank you for all you’ve done and continue to do with us. Our work isn’t done yet, and we can’t wait to celebrate many more anniversaries with you.