Epigenetic misprogramming is an essential component of cancer development.
DNA methylation-based risk-prediction models provide novel opportunities for risk-tailored screening and prevention of cancer.
Multidisciplinary collaborative research is needed to overcome the scientific challenges associated with the discovery of DNA methylation markers for risk-prediction, such as identifying surrogate tissues and developing novel analytical methods.
Implementation of epigenome-based risk-tailored screening and prevention programmes requires several ethical, legal, social, organizational and economic challenges to be addressed in addition to the engagement of policymakers, health-care professionals and the public.
The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements. However, the development and implementation of DNA methylation-based risk-prediction tests poses considerable challenges. In particular, the cell type specificity of DNA methylation and the extensive cellular heterogeneity of the easily accessible surrogate cells that might contain information relevant to less accessible tissues necessitates the use of novel methods in order to account for these confounding issues. Furthermore, the engagement of the scientific community with health-care professionals, policymakers and the public is required in order to identify and address the organizational, ethical, legal, social and economic challenges associated with the routine use of epigenetic testing.
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The authors' research is supported by the European Union's Horizon 2020 Programme (H2020/2014-2020) under grant agreement number 634570 (Project FORECEE: www.forecee.eu/). M.W. also receives support from the European Research Council (ERC Advanced Grant ERC-BRCA) and The Eve Appeal (www.eveappeal.org.uk/). The authors acknowledge the support of the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre.
The authors declare no competing financial interests.
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Widschwendter, M., Jones, A., Evans, I. et al. Epigenome-based cancer risk prediction: rationale, opportunities and challenges. Nat Rev Clin Oncol 15, 292–309 (2018). https://doi.org/10.1038/nrclinonc.2018.30
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