At 48, Jenny Singleton got breast cancer. At 66, her mother did, too.
"When my breast cancer was diagnosed, I immediately thought we must have a gene for it," Jenny Singleton said. "So I was tested and I didn't have the BRCA gene. And so that's often left me wondering, well, then why is it that my mom and I both got breast cancer?"
Cancer susceptibility genes are estimated to account for only 5 to 10 percent of breast cancers overall. Now the Singletons and thousands of other families are part of a study that is looking to see if there is evidence that environmental exposures in the uterus during pregnancy could account for some breast cancers later in life.
Barbara Cohn, director of the Child Health and Development Studies, looks through participant files collected over 56 years.
Epidemiologist Barbara Cohn is leading this research. Cohn is the director of the Child Health and Development Studies project in Oakland, Calif.
From 1959 to 1967, the group's researchers enrolled some 20,000 pregnant women — including Jenny's mother, Bernice — in a long-term study to track their health and the health of their children.
Over the past five decades, the researchers have tracked those families, using the data to investigate everything from the effects of smoking and exposure to pesticides during pregnancy, to possible causes of schizophrenia.
Cohn is using blood samples taken during pregnancy to test her hypothesis that pregnancy is a particularly vulnerable time to be exposed to environmental chemicals. "To our knowledge, we're doing the very first what I call 'womb to breast cancer' study in the world," she said.
Health researchers in this field sometimes say that genetics load the gun, but the environment pulls the trigger. But finding that trigger is hard. Cohn is hoping to pinpoint chemicals in the pregnant mothers' blood that might be associated with a greater risk of breast cancer in their daughters, more than 50 years after they were born.
Standard labs conduct this kind of research by testing for the presence of specific chemicals, one by one — a labor-intensive process. "One chemical at a time is never probably going to give us the whole answer," Cohn said.
That's why Cohn has turned to Dean Jones, director of the clinical biomarkers laboratory at Emory University in Atlanta. His lab uses ultra-high-resolution mass spectrometer to analyze tens of thousands of chemicals at once using just a drop of blood. His team has also developed computerized algorithms to analyze how the body processes the chemicals it is exposed to.
The sum of those exposures to environmental risk factors over a lifetime is something that Jones and other researchers call the "exposome."
Find other stories in the Living Cancer series at WNYC.org.
Jones said that "sequencing the human genome was the easy part; now we're trying to sequence the human exposome." Jones and others are trying to come up with a map of how our bodies react to all of those exposures. His lab is part of the first exposome center funded by the National Institute of Environmental Health Sciences.
Cohn and Jones' collaboration is just beginning to show some results. When Jones tested Cohn's study samples, he found that the mothers of daughters with cancer had irregularities in the way they appeared to metabolize linoleate, an essential fatty acid. Jones doesn't know yet why or how an exposure could trigger that problem. But if he can understand the mechanism, he'll have a shot at figuring out how to prevent or reverse the change.
Jones' goal is to be able to analyze a million chemicals someday and come up with an affordable clinical test that doctors could use routinely to predict health outcomes based on specific biomarkers, "so that we can develop what I call a health forecasting system," Jones says.
The research and technology aren't there yet, but Cohn and Jones are determined to get them closer.
Our series is produced with member station WNYC, and with WETA, whose documentary Cancer: The Emperor of All Maladies will air on PBS in March.
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Transcript
DAVID GREENE, HOST:
We are returning to our series Living Cancer produced with member station WNYC. Our focus this morning - research into breast cancer and figuring out what, if anything, in our day-to-day environment causes it. This kind of research has proceeded slowly, but that's beginning to change.
A new field is emerging that aims to look at the totality of our lifelong exposures to the environment. Scientists call it exposome, how our genes interact with substances in the air we breathe, the food we eat, the chemicals we absorb. Paige Cowett from member station WNYC visited two researchers who are undertaking a massive study, starting with tens of thousands of samples taken from women over the last 55 years.
PAIGE COWETT, BYLINE: One of the women in this big study is Jenny Singleton. She got breast cancer at age 48. So did her mother at age 66.
JENNY SINGLETON: And, of course, when my breast cancer was diagnosed, I immediately thought we must have a gene for it. That must be the case. So I was tested. I didn't have the BRCA gene.
COWETT: And that's left her wondering.
SINGLETON: Why is it that my mom and I both got breast cancer? And so, Barbara, do you have an answer for us yet (laughter)?
COWETT: Barbara is Barbara Cohn, an epidemiologist who's in charge of the study on child health and development.
BARBARA COHN: If I did, I wouldn't maybe have to send you any more questionnaires ever again.
COWETT: The questionnaires are part of Cohn's study. It started way back in 1959 to track women's health from pregnancy onward. Twenty-thousand pregnant women enrolled, and when their kids were born, they were enrolled, too. Jenny Singleton is one of those kids.
All right. Should we go to the fridge?
To see where the Singleton samples are stored, I went to the bio repository at UC Berkeley. There are 300,000 vials of blood, urine and saliva here in giant nitrogen tanks and in rows and rows of deep freezers.
And how cold is it in there?
UNIDENTIFIED WOMAN #1: This is minus 80 degrees Celsius. So really cold.
COWETT: The samples from the study have been collected over the past 55 years, and they've been used to investigate a lot of things - the effects of smoking during pregnancy, exposure to pesticides, possible root causes of schizophrenia. And now Barbara Cohn is using them to study breast cancer.
COHN: To our knowledge, we're doing the very first, what I call, womb-to-breast-cancer study in the world.
COWETT: Cohn wants to find out if chemical exposures while you're in the womb might contribute to getting breast cancer later. She's testing a hypothesis that the timing of exposures is important, that it's not just if you're exposed to chemicals, but when, that there are moments when women are most vulnerable.
COHN: We are finding relationships between environmental chemicals in the blood of mothers and the breast cancer risk of daughters.
COWETT: But even if there seems to be a relationship between one kind of chemical and an increased risk, Cohn can't say that it caused cancer. Those chemicals might just be bystanders. The line you hear from cancer researchers in this field is your genetics load the gun, the environment pulls the trigger. But finding the trigger is hard. And Cohn needs much more firepower in the lab if she's going to sort through all the possibilities and nail it down.
COHN: One chemical at a time is never, probably, going to give us the whole answer.
COWETT: Standard labs can't test more than a few chemicals at a time without using up more precious sample than Cohn has. So she has to choose which chemicals to test for one by one. That's why she turned to Dean Jones and his team at the clinical biomarkers lab at Emory University. They've been doing something totally new that should speed things up a lot.
DEAN JONES: This is a high-resolution mass spectrometer.
COWETT: Jones and an assistant are showing Cohn a $750,000 machine that can analyze tens of thousands of chemicals with a single drop of blood. And using that same sample, he can also measure how a person's body responds to those exposures.
UNIDENTIFIED WOMAN #2: So now we're actually running 66 samples in a 24-hour time period.
COHN: I mean, that's amazing.
UNIDENTIFIED WOMAN #2: Yeah.
COHN: This study wouldn't even be remotely possible even two years ago.
UNIDENTIFIED WOMAN #2: Right, right.
COWETT: The combination of being able to detect so many chemicals in a single analysis and being able to understand how the person metabolized them means that Dean Jones could get much closer to understanding whether a chemical exposure could lead to cancer. And when he tested Cohn's samples, he started to see a difference between the mothers whose daughters got cancer and the mothers of daughters who stayed well.
JONES: We see an illustration of the pathways that are potentially contributing to or marking that difference.
COWETT: He sees what he calls a dysregulation - something out of whack. The mothers whose daughters got breast cancer metabolized an essential fatty acid, linoleate, differently from the mothers whose daughters didn't get sick. He doesn't yet know why or how this difference is linked to the disease, whether it has to do with environmental chemicals or not. But if he can find out why that process faltered, he'll be a giant step closer to being able to predict or reverse that change and possibly prevent cancer. It's a monumental task.
JONES: Sequencing the human genome was the easy part. Now we're trying to sequence the human exposome.
COWETT: The exposome, the entirety of all of our lifelong environmental exposures, a map of how our bodies react to all of those encounters. The idea is, if you have a map of exposures, you could find a detour around cancer.
COHN: This is the holy grail. And I would love to say we're going to find it next week. I doubt it.
JONES: I don't think it's impossible. The challenge is to get an affordable test so that we can develop what I call a health forecasting system.
COWETT: What he means is a blood test that would reveal biomarkers of risk, changes in your body that indicate that disease is coming. And while genetic biomarkers like BRCA 1 are useful, what's needed is a marker that can help you avoid an exposure at a critical time or alter a process in your body to avoid risk. That's the holy grail.
JONES: I think the challenge is really the unknown. That's the excitement that I have about the new technologies, is it really gives us the ability to know.
COWETT: And knowing more about how people process chemical exposures also means that regulators would know more about the health risks of products before they make it to the shelves in the first place. That knowledge isn't there yet. But Barbara Cohn and Dean Jones think they're getting close. For NPR News, I'm Paige Cowett in New York.
(SOUNDBITE OF MUSIC)
GREENE: And Paige's story if part of our series Living Cancer. It is produced with mentioned WNYC and with WETA, whose documentary, "Cancer: The Emperor Of All Maladies," will air on PBS next month. Transcript provided by NPR, Copyright NPR.
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