Keynote Abstract




Paolo Vineis
Imperial College London
The internal exposome – a global approach to a better understanding of human disease.

It is generally accepted that the majority of important chronic diseases are likely to result from the combination of environmental exposures to chemical and physical stressors and human genetics. There is also evidence that the effects are location-specific and influenced by lifestyle and socioeconomic characteristics. Although information on both environmental and genetic causes of disease is growing as a result of large-scale epidemiological research, exposure data (including diet, lifestyle, environmental and occupational factors) is often fragmentary (in time and depth), non-standardized, at crude resolution and often does not include estimates at the level of the individual. The information on environmental factors is often incomplete or inaccurate and the subsequent estimation of overall risks associated with these factors is severely hindered. As a result, important associations can go undetected. This limitation has recently been framed within the context of the exposome, the environmental counterpart of the genome. The concept of the exposome refers to the totality of environmental exposures from conception onwards and has been described in detail elsewhere including its external and internal components (Wild, 2005; Rappaport and Smith, 2010; Anon, 2016; Vineis et al.,2009). The exposome approach has been proposed to improve the identification of environmental risk factors for disease, by applying to epidemiological research new tools emerging from exposure sciences and high-throughput omic technologies. Environmental contaminants have been argued to lead to the perturbation of one or more “Adverse Outcome Pathways” which consist of a sequence of events including molecular initiating events, biochemical responses, cellular responses, tissue organ responses, individual responses and lastly population responses. Pathway perturbation can be used as a conceptual framework for organising and evaluating the strength of existing evidence concerning steps necessary for progressing from molecular initiating events to an adverse outcome. Pathway perturbation makes particularly sense within the causal model called the “sufficient-component-cause framework”. This considers exposures or hits that together lead to the outcome under consideration. The model provides a way to account for how multiple factors, whether environmental exposures or genes, combine to result in disease in an individual or population. Another important component of the “pathway perturbation” paradigm is the life-course approach. The early stages of life allow individuals to build up their ability to respond to strains of different kinds (chemical, physical, biological and psychological) and this response “build-up” constitutes a “reserve” that allows variable resilience, very often depending on socio-economic status in addition to environmental and behavioural agents. These concepts have been systematically developed in the context of the US National Academy of Sciences 2st Century Risk Assessment report (NAS 2017), that refers extensively to the exposome.

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