Exposome

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The exposome encompasses the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome, first proposed in 2005 by a cancer epidemiologist. The concept of the exposome and how to assess it has led to lively discussions with varied views. As of 2016 it may not be possible to measure or model the full exposome, several European projects such as HELIX, EXPOsOMICS, and HEALS and the U.S. initiative HERCULES have started to make first attempts.

Definition[edit]

The exposome encompasses the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome. It was first proposed in 2005 by a cancer epidemiologist, in an article entitled "Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology".[1] The concept of the exposome and how to assess it has led to lively discussions with varied views in 2010,[2][3]2012[4][5][6][7][8][9] and 2014,[10][11]

In his 2005 article Wild stated, "At its most complete, the exposome encompasses life-course environmental exposures (including lifestyle factors), from the prenatal period onwards." The concept was first proposed to draw attention to the need for better and more complete environmental exposure data for causal research, in order to balance the investment in genetics. Per Wild even incomplete versions of the exposome could be useful to epidemiology. In 2012 Wild outlined methods, including personal sensors, biomarkers and 'omics' technologies, to better define the exposome.[4] He described three overlapping domains within the exposome:

  1. a general external environment including the urban environment, education, climate factors, social capital, stress,
  2. a specific external environment with specific contaminants, radiation, infections, lifestyle factors (e.g. tobacco, alcohol), diet, physical activity, etc.
  3. an internal environment to include internal biological factors such as metabolic factors, hormones, gut microflora, inflammation, oxidative stress.

In late 2013 this definition was explained in greater depth in the first book on the exposome.[12][13] In 2014, the same author revised the definition to include the body's response with its endogenous metabolic processes which alter processing of chemicals.[14]

Measurement[edit]

For complex disorders specific genetic causes appear to only account for 10-30% of the disease incidence, but there has been no standard or systematic way to measure the influence of environmental exposures. Some studies into the interaction of genetic and environmental factors in the incidence of diabetes have demonstrated that "environment-wide association studies" (EWAS, or exposome-wide association studies) may be feasible.[15][16] However, it is not clear what data sets are most appropriate to represent the value of "E".[17]

In July 2017, saliva was suggested as a practical specimen to measure the human exposome, and because it is easy to collect, to analyse it repeatedly in longitudinal EWAS. The authors found concentrations of 1,233 chemicals and 169 metabolites had been detected in saliva per their literature and saliva–metabolome database review, which fit into 49 metabolic pathways.[18]

Research initiatives[edit]

As of 2016 it may not be possible to measure or model the full exposome, but several European projects have started to make first attempts. In 2012, the European Commission awarded two large-grants to pursue exposome-related research.[19]

The HELIX project at the Barcelona-based Centre for Research in Environmental Epidemiology will attempt[when?] to develop an early life exposome, noting that the first exposures occur during development.[9][20] It will build upon six existing birth cohorts across Europe and measure the exposome at key prenatal and early childhood time points, through the use of GIS, personal sensors, biomarkers and omics platforms.

A second project, Exposomics, based at Imperial College London will use[when?] smartphones which utilize GPS and environmental sensors to assess exposures.[21][19][22]

In late 2013, a major initiative called the "Health and Environment-Wide Associations based on Large Scale population Surveys" or HEALS began. Touted as the largest environmental health-related study in Europe, HEALS proposes to adopt a paradigm defined by interactions between DNA sequence, epigenetic DNA modifications, gene expression and environmental factors.[23]

In December 2011, the US National Academy of Sciences hosted a meeting entitled "Emerging Technologies for Measuring Individual Exposomes."[24] A Centers for Disease Control and Prevention overview "Exposome and Exposomics" outlines the three priority areas for researching the occupational exposome as identified by the National Institute for Occupational Safety and Health.[7] The National Institutes of Health (NIH) has invested in technologies supporting exposome-related research, including biosensors, and supports research on gene-environment interactions.[25][26] In May, 2013, the National Institute of Environmental Health Sciences (NIEHS) awarded a Core Center Grant to Emory University´s exposome project HERCULES. [27]

Proposed Human Exposome Project (HEP)[edit]

The idea of a Human Exposome Project, analogous to the Human Genome Project, has been proposed and discussed in numerous scientific meetings, but as of 2017 no such project exists. Given the lack of clarity on how science would go about pursuing such a project, support has been lacking.[28] Reports on the issue include:

Related fields[edit]

The concept of exposome has contributed to the 2010 proposal of a new paradigm in disease phenotype, "the unique disease principle": Every individual has a unique disease process different from any other individual, considering uniqueness of the exposome and its unique influence on molecular pathologic processes including alterations in the interactome.[32] This principle was first described in neoplastic diseases as "the unique tumor principle".[33] Based on this unique disease principle, the interdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathology and epidemiology.[34]

See also[edit]

References[edit]

  1. ^ Wild, CP (Aug 2005). "Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology". Cancer Epidemiology, Biomarkers & Prevention. 14 (8): 1847–50. PMID 16103423. doi:10.1158/1055-9965.EPI-05-0456. 
  2. ^ Rappaport SM, Smith MT (2010). "Epidemiology. Environment and disease risks". Science. 330 (6003): 460–461. doi:10.1126/science.1192603. 
  3. ^ Rappaport SM (2011). "Implications of the exposome for exposure science". J Expo Sci Environ Epidemiol. 21 (1): 5–9. doi:10.1038/jes.2010.50. 
  4. ^ a b Wild, CP (Feb 2012). "The exposome: from concept to utility". International Journal of Epidemiology. 41 (1): 24–32. PMID 22296988. doi:10.1093/ije/dyr236. 
  5. ^ Peters A, Hoek G, Katsouyanni K (2012). "Understanding the link between environmental exposures and health: does the exposome promise too much?". Epidemiol Community Health. 66: 103–105. doi:10.1136/jech-2011-200643. 
  6. ^ Buck Louis GM, Sundaram R (2012). "Exposome: time for transformative research". Stat Med. 31 (22): 2569–75. doi:10.1002/sim.5496. 
  7. ^ a b Centers for Disease Control and Prevention (2012). "Exposome and Exposomics". Retrieved 5 March 2013.
  8. ^ Buck Louis G. M.; Yeung E.; Sundaram R.; et al. (2013). "The Exposome – Exciting Opportunities for Discoveries in Reproductive and Perinatal Epidemiology". Paediatric and Perinatal Epidemiology. 27: 229–236. doi:10.1111/ppe.12040. 
  9. ^ a b Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, et al. "The Human Early-Life Exposome (HELIX): Project Rationale and Design". Environ Health Perspect. doi:10.1289/ehp.1307204. 
  10. ^ Miller Gary W.; Jones Dean P (2014). "The Nature of Nurture: Refining the Definition of the Exposome". Toxicological Sciences. 137 (1): 1–2. PMC 3871934Freely accessible. PMID 24213143. doi:10.1093/toxsci/kft251. 
  11. ^ Porta M, editor. Greenland S, Hernán M, dos Santos Silva I, Last JM, associate editors (2014). A dictionary of epidemiology, 6th. edition. New York: Oxford University Press. ISBN 9780199976737
  12. ^ Gary Miller (2 December 2013). "The Exposome: A Primer". Elsevier. p. 118. ISBN 978-0124172173. Retrieved 16 January 2014. 
  13. ^ Gary Miller (20 November 2013). "G x E = ?". Sci Connect. Elsevier. Retrieved 16 January 2014. 
  14. ^ Miller Gary W.; Jones Dean P. (January 2014). "The Nature of Nurture: Refining the Definition of the Exposome". Toxicological Sciences. 137 (1): 1–2. PMC 3871934Freely accessible. PMID 24213143. doi:10.1093/toxsci/kft251. 
  15. ^ Patel, CJ; Bhattacharya, J; Butte, AJ (May 20, 2010). "An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus.". PLoS ONE. 5 (5): e10746. PMC 2873978Freely accessible. PMID 20505766. doi:10.1371/journal.pone.0010746. 
  16. ^ Patel, CJ; Chen, R; Kodama, K; Ioannidis, JP; Butte, AJ (20 January 2013). "Systematic identification of interaction effects between genome- and environment-wide associations in type 2 diabetes mellitus" (PDF). Human Genetics. 132 (5): 495–508. PMC 3625410Freely accessible. PMID 23334806. doi:10.1007/s00439-012-1258-z. Retrieved 4 March 2015. [dead link]
  17. ^ Smith Martyn T.; Rappaport Stephen M. (August 2009). "Building Exposure Biology Centers to Put the E into "G × E" Interaction Studies". Environmental Health Perspectives. 117 (8): A334–A335. PMC 2721881Freely accessible. PMID 19672377. doi:10.1289/ehp.12812. 
  18. ^ Vincent Bessonneau, Janusz Pawliszyn, and Stephen M. Rappaport. The Saliva Exposome for Monitoring of Individuals’ Health Trajectories. Environ Health Perspect; JUly 2917, Vol 125, issue 7, DOI:10.1289/EHP1011
  19. ^ a b Callaway, Ewen (27 November 2012). "Daily dose of toxics to be tracked". Nature. Retrieved 4 March 2013. 
  20. ^ HELIX | Building the early life exposome EU
  21. ^ "Imperial College News.". Retrieved 21 January 2013. 
  22. ^ About Exposomics EU
  23. ^ "HEALS-EU.". Retrieved 16 January 2014. 
  24. ^ "National Academy of Sciences meeting". Retrieved 21 January 2013. 
  25. ^ "NIEHS Gene-Environment studies". Retrieved 21 January 2013. 
  26. ^ "Genes and Environment Initiative". Retrieved 21 January 2013. 
  27. ^ "Emory HERCULES Exposome Center". Retrieved 15 January 2014. 
  28. ^ Arnaud, Celia Henry (16 August 2010). "Exposing The Exposome". Chemical & Engineering News, Vol. 88, No. 33, pp. 42-44. American Chemical Society. Retrieved 5 March 2013.
  29. ^ Lioy, PJ; Rappaport, SM (Nov 2011). "Exposure science and the exposome: an opportunity for coherence in the environmental health sciences". Environmental Health Perspectives. 119 (11): A466–7. PMC 3226514Freely accessible. PMID 22171373. doi:10.1289/ehp.1104387. 
  30. ^ "NRC report supports NIEHS vision of the exposome". Retrieved 21 January 2013. 
  31. ^ "Exposure Science in the 21st Century: A Vision and a Strategy". Retrieved 21 January 2013. 
  32. ^ Ogino S, Lochhead P, Chan AT, et al. (2013). "Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease". Mod Pathol. 26: 465–484. PMC 3637979Freely accessible. PMID 23307060. doi:10.1038/modpathol.2012.214. 
  33. ^ Ogino S, Fuchs CS, Giovannucci E (2012). "How many molecular subtypes? Implications of the unique tumor principle in personalized medicine". Expert Rev Mol Diagn. 12: 621–628. PMC 3492839Freely accessible. PMID 22845482. doi:10.1586/erm.12.46. 
  34. ^ Ogino S, Stampfer M (2010). "Lifestyle factors and microsatellite instability in colorectal cancer: the evolving field of molecular pathological epidemiology". J Natl Cancer Inst. 102: 365–367. PMC 2841039Freely accessible. PMID 20208016. doi:10.1093/jnci/djq031.