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Superfund researchers propose exposome paradigm

By Rebecca Wilson
December 2010

Stephen Rappaport, Ph.D.
Rappaport is director and principal investigator of the Berkeley Center for Exposure Biology, a multidisciplinary program with the goal of developing a new generation of biomarkers and biosensors for environmental epidemiology. (Photo courtesy of Stephen Rappaport)

Martyn Smith, Ph.D.
Smith, above, and Rappaport are two of the co-directors of the Berkeley Genes and Environment Laboratory where they study the adverse effects of chemicals on human health and how genetic variation contributes to these effects and disease susceptibility. (Photo courtesy of Martyn Smith)

NIEHS Superfund Research Program (SRP) grantees Stephen Rappaport, Ph.D., and Martyn Smith, Ph.D., published a perspective on environmental health study design in the Oct. 22 edition of Science magazine. In the perspective, Rappaport and Smith, who are researchers in the University of California-Berkeley SRP (http://superfund.berkeley.edu/) Exit NIEHS, offer a fundamental - and possibly controversial - proposal for changing the way epidemiologists measure environmental exposure.

The article, titled "Environment and Disease Risks," (http://www.sciencemag.org/cgi/content/summary%20/330/6003/460) Exit NIEHS presents a compelling argument that a more complete and objective picture is needed in order to help investigators discover the major causes of chronic diseases by better accounting for an individual's total environmental exposure, or exposome.

Although current evidence indicates that environmental, not genetic, factors are primarily responsible for the risks of developing chronic diseases, Rappaport and Smith point out that epidemiologists use sophisticated genome-wide association studies (GWAS) to investigate disease prevalence while relying upon participant questionnaires to identify environmental exposures. The researchers add that the inherent inaccuracy and imprecision in questionnaire data diminish the value of detailed - and costly - genetic data and can lead to biased inferences regarding gene-environment interactions.

To remedy some of these biases, Rappaport (http://ehs.sph.berkeley.edu/people/rappaport.htm) Exit NIEHS and Smith (http://ehs.sph.berkeley.edu/people/smithm.htm) Exit NIEHS suggest that scientists adopt the concept of the exposome to conduct the environmental equivalent of GWAS.

The exposome

Originally defined by Christopher Wild, Ph.D., director of the World Health Organization's International Agency for Research on Cancer, the exposome represents the totality of environmental exposures received by a person from conception onward. Rappaport and Smith stress that the exposome includes all toxic chemicals present in a person's internal chemical environment where disease processes originate. Evaluating the exposome is important because internal chemical environment reflects the combined effects of contaminants from air, water, and food, as well as toxic chemicals produced in the body as a result of inflammation, oxidative stress, lipid peroxidation, infections, gut flora, and other natural processes.

The authors state that peoples' exposomes can be characterized using either a top-down or a bottom-up strategy at each time point of interest. While a bottom-up strategy would entail measuring all chemicals in each external source of a person's exposure, a top-down approach would focus on all chemicals - or toxicant classes - in a subject's blood. Rappaport and Smith recommend the top-down approach because it is more efficient and would detect all toxicants in the internal chemical environment, not just those from air, water, and food. They suggest that initial studies could use archived blood samples from large prospective cohort studies for proof of concept.

Rappaport and Smith argue, "Characterizing the exposome represents a technological challenge like that of the human genome project," and the tools and technologies required to accomplish the task could well "motivate the development of commercial devices for screening important environmental exposure in blood samples." They conclude by speculating that the marriage of exposomes and genomes would lead to powerful studies able to closely examine gene-environment interactions and their role in the prevalence of chronic disease. "Such a union," they add, "might even push the nature-versus-nurture debate toward resolution."

Citation: Rappaport SM, Smith MT (http://www.sciencemag.org/cgi/content/summary%20/330/6003/460) Exit NIEHS. 2010. Environment and Disease Risks. Science 330(6003):460-461. Summary (http://www.niehs.nih.gov/news/newsletter/2010/december/science-extramural.cfm#two)

(Rebecca Wilson is an environmental health information specialist for MDB, Inc., a contractor for the NIEHS Superfund Research Program and Worker Education and Training Program.)



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