Genetics and the Environment - The Environmental Genome Project

In many instances it is difficult to understand how genes manage to assert themselves over the myriad of complications imposed by the environment. The Environmental Genome Project (EGP) was launched by the National Institute of Environmental Health Sciences (NIEHS, which is one of the twenty-seven institutes and centers of the NIH) in 1998. The EGP aims to improve understanding of human genetic susceptibility to environmental exposures, including gaining an understanding of how individuals differ in their susceptibility to environmental agents and how these susceptibilities change over time. Figure 4.2 shows the interrelationship of human health and disease to environmental exposures, susceptibility, time, and age.

To date, EGP researchers are investigating sensitivities to selected environmental agents such as chemicals and pharmaceuticals using gene identification and testing. The results of this research will assist in protecting sensitive populations at potentially lower regulatory costs and will help to direct public health policy by assisting regulators to determine whether existing and proposed environmental regulations are appropriate and in the best interest of public health. Genetic research will also aid in calculating the number of people who benefit from regulatory action.

The first of three phases of research focuses on polymorphic variants in a range of 200 genes, mainly targeted to those that regulate DNA repair and the cell cycle. During phase I, the NIEHS developed a publicly accessible database of human DNA variation, initiated studies of human haplotypes (sets of alleles or markers on short chromosome segments), and established a program that uses mouse models to help understand functional analysis of human environmentally associated disease genes. Phase I resulted in the identification of many thousands of polymorphisms in several hundred genes and also included investigation of the ethical, legal, and social issues related to EGP research and the development of technology and informatics (the science of information management applied to the information needs of health care workers and patients) to support the project.

FIGURE 4.2
Human genetic susceptibility to environmental exposures
SOURCE: "The Mission of the EGP," in Environmental Genome Project, U.S. Department of Health and Human Services, National Institutes of Health, The National Institute of Environmental Health Sciences, May 5, 2005 (accessed February 7, 2005)

The second phase of the project will include identification and research of genes regulating metabolism, signal transduction (conversion of a signal of one type into another), and apoptosis (programmed cell death). Ultimately, the EGP will resequence at least 554 genes identified by the NIEHS scientific community, and additional genes may be added over time. The NIEHS also plans targeted screening of certain populations that are at high risk of developing specific diseases.

According to Kenneth Olden, the NIEHS director, the project's first phase is complete, and researchers have resequenced and cataloged 200 environmentally responsive genes, identifying links to vascular disease, leukemia, and other conditions that affect the quality and length of life of many Americans. One of the project's results has been the identification of a gene variation that will assist in identifying individuals at increased risk for prostate cancer. The discovery that the NKX3.1 gene is involved in the disease process provides researchers with a specific set of DNA pathways to target for more effective therapies. In a news release issued April 16, 2003, Olden stated that "under the Institute's leadership, the Environmental Genome Project has enabled the health science community to take a major step forward in understanding and potentially preventing environmentally induced disease in susceptible individuals. We have great hope about our ability to map environmental factors in disease."

Phase II of the EPG focused on analyses of the polymorphisms identified during phase I. A June 2004 symposium focused on recent findings concerning the function of DNA repair and cell cycle control genes and how these functions are altered by naturally occurring polymorphisms in the human population. The EGP symposium presented research studies intended to help identify and characterize polymorphisms relevant for environment-related diseases.

The results of EGP research about the interaction between genes and the environment will likely have an enormous impact on health care. Testing for genes that indicate environmental susceptibility will be particularly beneficial if known prevention techniques and therapies exist. Knowledge of their genetic identities will alert people at higher than average risk of developing specific diseases to take precautions to avoid risk factors and may help to reduce the occurrence of conditions such as asthma, diabetes, heart disease, breast and colon cancer, and Parkinson's.

The EGP also informs decision making by providing data and evidence-based recommendations to resolve the debate over regulating toxic substances such as pesticides and mercury. Some industry observers and states claim that regulatory agencies issue guidelines and apply sanctions in response to public outcries rather than scientific evidence—they believe the industry may be overregulated because decision-makers lack objective scientific data. Resolutions passed in 1998 and 1999 by seven states—Colorado, Georgia, Kansas, Missouri, Michigan, Pennsylvania, and Wyoming—expressed this concern. These resolutions urged the Environmental Protection Agency (EPA) to use sound science, to make no decisions unless adequate data is available, and to avoid actions that will have adverse economic effects when evaluating or instituting new pesticide standards under the Food Quality Protection Act.

On December 19, 2003, the EPA, in a decision informed by findings of the EGP, signed a rule to reduce mercury emissions from power plants. During 2003 and 2004, thirty-nine states proposed regulations or passed legislation to reduce mercury emissions to air, land, and water. Resolutions and acts (bills enacted into law) addressed a wide range of issues, including banning the sale of certain mercury-containing products, enacting product-labeling legislation, establishing disposal bans and establishing education, and collection programs for mercury and mercury-containing products.