Expanding Genome Integrity Assays to Population Studies
The consortium, Expanding Genome Integrity Assays to Population Studies, was formed through a solicitation (RFA-ES-17-006) in 2017, issued by the National Institute of Environmental Health Sciences (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 or cigarette smoke, or from diet, such as high sugar intake, harms our DNA, leading to disease in some 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 population studies, which have assisted in establishing promising methods of determining genome integrity capacity. 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 on existing and new genome integrity tools to meet the needs of epidemiological studies. Epidemiological, clinical, or population investigations involving human subjects are focused on associations between environmental stressors and the risk of environmentally influenced disorders, and integrated with supporting studies of assay development.
Relevant assays include measures of overall DNA repair capacity or of individual repair pathways, mutagenesis, 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 are assays that have been pilot tested on various human populations, as well as animal and cell models, which provide a working measure of ability to ward off or repair damage to DNA or chromosomes and the likely consequences of such damage. The human studies and clinical research that utilize established or prototypic assays of genome integrity are required with a focus on evaluating and optimizing tools to determine indicators and biomarkers of altered genome integrity and the interpretation of results.