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Roadmap for investigating epigenome deregulation and environmental origins of cancer |
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| Authors: | Zdenko Herceg Christopher P. Wild Athena Sklias Lavinia Casati Susan J. Duthie Rebecca Fry Jean‐Pierre Issa Richard Kellermayer Igor Koturbash Yukata Kondo Johanna Lepeule Sheila C.S. Lima Carmen J Marsit Vardhman Rakyan Richard Saffery Jack A. Taylor Andrew E. Teschendorff Toshikazu Ushijima Paolo Vineis Cheryl Lyn Walker Robert A. Waterland Joe Wiemels Srikant Ambatipudi Davide Degli Esposti Hector Hernandez‐Vargas |
| Affiliation: | 1. International Agency for Research on Cancer (IARC), 150 Cours Albert‐Thomas, Lyon, FranceZ.H. and A.G. contributed equally to this work;2. International Agency for Research on Cancer (IARC), 150 Cours Albert‐Thomas, Lyon, France;3. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy;4. School of Pharmacy and Life Sciences, The Robert Gordon University, Aberdeen, United Kingdom;5. Gillings School of Global Public Health, UNC, Chapel Hill, NC;6. Fels Institute for Cancer Research & Molecular Biology, Philadelphia, PA;7. Texas Children's Hospital, Baylor College of Medicine, TX;8. University of Arkansas for Medical Sciences, AR;9. Aichi Cancer Center Research Institute, Nagoya, Japan;10. INSERM, Albert Bonniot Institute, Grenoble, France;11. National Cancer Institute (INCA), Rio de Janeiro, Brazil;12. Emory University, Atlanta, GA;13. Centre for Genomics and Child Health, Blizard Institute, London, United Kingdom;14. Murdoch Childrens Research Institute, Melbourne, Australia;15. National Institute of Health, NC;16. Statistical Cancer Genomics, UCL Cancer Institute & Dept. of Woman's Cancer, University College London, United Kingdom;17. CAS‐MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Shanghai, China;18. National Cancer Center Research Institute, Tokyo, Japan;19. MRC/PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK;20. Departments of Molecular & Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX;21. Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, TX;22. UCSF School of Medicine, Epidemiology & Biostatistics, San Francisco, CA |
| Abstract: | The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene–environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor‐specific (“fingerprints”) that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed and advances in epigenomics that may help in understanding the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed and how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment. |
| Keywords: | epigenetics environment cancer molecular mechanisms research gaps perspectives biomarkers |