Linking Environmental Chemicals to Disease

The team found significant associations between people with diabetes and their exposure to heptachlor epoxide, a pesticide that was partially banned in 1988, and also to gamma-tocopherol, an ingredient that appears in some versions of vitamin E.

Specifically, people with detectable levels of heptachlor epoxide in their blood were more likely to have sugar levels in their blood associated with diabetes–with an odds ratio of 1.7. For the gamma-tocopherol form of vitamin E the odds ratio was 1.5. In contrast, high beta-carotene levels were slightly protective against diabetes with an odds ratio of 0.6.

“We’ve known for decades that environmental factors play a major role in diseases like diabetes, cancer and heart disease,” said Jeremy Berg, PhD, to Science Daily. He’s the director of the National Institute of General Medical Sciences, which partially supported the research. “By enabling us to measure the impact of these factors, this new approach will shed light on how genes and the environment influence our health and could provide insights into new ways to control some of our nation’s most serious health problems.”

Butte and coauthors Chirag Patel and Jayanta Bhattacharya have borrowed a page from genome-wide association studies that compare populations with and without a disease or trait (cancer, blue eyes) and scan the DNA of the people in that population to ferret out genetic markers that have a high statistical correlation with that trait.

Researchers can then use statistics to determine risk factors for people who carry a genetic variation associated with the trait, providing a probability of, say, a 20 percent higher than average risk that a person will have a heart attack, or an eight-times risk that they will one day suffer from macular degeneration.

Epidemiologists and public health experts have long collected data linking or trying to link environmental exposures of toxins – everything from herbicides to dioxins and cigarette smoke – to cancer and other diseases. Nearly all of these studies, however, are reactions to known or suspected exposures in a home or workplace; to pollution emergencies; and to other specific instances where people have or may have come into contact with a specific toxin.

Other traditional studies are hypothesis-driven efforts to solve epidemiological mysteries such as why breast cancer rates are unusually high in certain regions of the country, or why autism rates are rapidly increasing.

What makes the EWAS different is that Butte’s team has rather ingeniously suggested an approach that can detect associations previously unsuspected using an approach that uniformly investigates hundreds or thousands of chemicals in the environment.

This approach could help solve a conundrum that has vexed investigators for decades: how to sort through and to understand the human impact of nearly 80,000 human-produced chemicals listed by the Environmental Protection Agency–many of which show up inside of people in trace amounts that have proven difficult to test for harmful effects.

(I have been tested for over 300 chemicals inside of me, and have detectable levels of several pesticides, heavy metals, dioxins, and much more. What this means for me or for anyone else is unclear since scientists have so far been unable to test the harm – or lack of harm – of trace amounts of these chemicals inside people).

EWAS will also allow researchers to better understand the impact of thousands of dietary “chemicals” that people ingest–from vitamins and supplements to sugars.

One caution: the EWAS approach has the same downside as GWAS studies, which offer statistical correlations that need to be clinically validated in real people to see if there is a true link between a genetic marker and a risk factor for a disease, or, in this case, between a chemical in the environment and a disease. For instance, recent clinical tests for certain GWAS markers associated with heart attack were found to be less important for determining risk than other factors such as family history.

Assuming the statistical models are replicated and validated by other researchers, EWAS analyses could provide a wealth of target chemicals to clinically investigate for true linkages with disease.

“This approach catapults us from being forced to ask very simple, directed questions about environment and disease into a new realm in which we can look at many, many variables simultaneously and without bias,” said Atul Butte to Science Daily. “In the future, we’ll be able to analyze the effectof genes and environment together, to find, perhaps, that a specific gene increases the risk of a disease only if the person is also drinking polluted well water.”