Omics biomarkers to study the internal exposome: the case of air pollution

Abstract

The majority of chronic diseases are likely to be the result of the combination of environmental exposures and human genetics. The exposome concept was proposed to increase our knowledge regarding the potential role of environment in the causation of disease. The exposome is a paradigm involving the study of all environmental exposures (e.g., air pollutants, chemical contaminants, diet or life style factors) and associated biological responses from conception until death. Once environmental exposures enter the human body they and their biological consequences become part of the internal exposome, which can be measured by OMICS technologies. Investigating perturbations in the internal exposome can provide information on direct measures of exposure or on physiological perturbations that are indicative of a certain exposure. Studying the internal exposome can provide biological underpinnings for empirically observed exposure-disease associations. In this thesis, we focused on air pollution, a high priority environmental pollutant responsible for 7 million premature deaths worldwide each year. Air pollution is recognized as a human carcinogen associated with lung cancer. It is also a major risk factor for other acute and chronic diseases including cardiovascular disease and chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. The overall aim of this thesis is to study three OMICS platforms (proteomics, transcriptomics, and DNA-methylomics) in relation to exposure to air pollution in order to have a better understanding of the biological processes that link air pollution exposure to health effects. When successful such analyses might contribute to generating insights on air pollution induced health effects, identifying air pollutant specific biological pathways, and detecting biomarkers of early disease.