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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.

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."

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.

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