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Expanding Genome Integrity Assays to Population Studies

The Expanding Genome Integrity Assays to Population Studies consortium was formed through a solicitation (RFA-ES-17-006) in 2017, issued by NIEHS and the National Cancer Institute (NCI). It supports cooperative agreements to develop and pilot test assays that will facilitate the wider use of genome integrity investigation into epidemiological and population studies. Genome integrity, here, refers to DNA repair (i.e., BER, NER, DR, or DDR), genome instability, and mutagenesis linked to exposures and variations in DNA repair capacity.

A constant barrage of harmful environmental chemicals — such as in air pollution and cigarette smoke — or from diet, such as high sugar intake, harms our DNA, leading to disease in some people but little to no noticeable effects in others. The ability to defend or restore DNA is at the heart of environmental health and our ability to reach a long, healthy life.

Through earlier initiatives, NIEHS took steps to bridge the gap from laboratory advances to human studies, which have helped establish promising methods of determining genome integrity at the level of the individual. Building on these earlier achievements, NIEHS and NCI issued the Request for Application based on recommendations of an expert panel (Nagel, et al. Mutat. Res. 2017. 800-802:14-28) to improve existing and develop new genome integrity tools to meet the needs of epidemiological studies.

Epidemiological, clinical, or population investigations involving human subjects focused on associations between environmental stressors and the risk of environmentally influenced disorders will benefit from new approaches to measure responses to environmental exposures. Relevant assays include measures of overall DNA repair capacity or of individual repair pathways, mutagenesis, and genome instability, as well as innovative measures of repair at the chromosomal level, provided that the endpoint reflects individual capacity to prevent or respond to damage.

Among the expected outcomes of this program are assays that have been pilot tested in human studies and provide information on an individual’s ability to repair damage to DNA or chromosomes that can lead to diseases and premature aging, as well as an individual’s response to cancer therapies.