Epigenome-based cancer risk prediction: Rationale, opportunities and challenges

Martin Widschwendter, Allison Jones, Iona Evans, Daniel Reisel, Joakim Dillner, Karin Sundström, Ewout W. Steyerberg, Yvonne Vergouwe, Odette Wegwarth, Felix G. Rebitschek, Uwe Siebert, Gaby Sroczynski, Inez D. De Beaufort, Ineke Bolt, David Cibula, Michal Zikan, Line Bjørge, Nicoletta Colombo, Nadia Harbeck, Frank DudbridgeAnne Marie Tasse, Bartha M. Knoppers, Yann Joly, Andrew E. Teschendorff, Nora Pashayan

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)292-309
Number of pages18
JournalNature Reviews Clinical Oncology
Volume15
Issue number5
DOIs
Publication statusPublished - May 1 2018

ASJC Scopus subject areas

  • Oncology

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    Widschwendter, M., Jones, A., Evans, I., Reisel, D., Dillner, J., Sundström, K., Steyerberg, E. W., Vergouwe, Y., Wegwarth, O., Rebitschek, F. G., Siebert, U., Sroczynski, G., De Beaufort, I. D., Bolt, I., Cibula, D., Zikan, M., Bjørge, L., Colombo, N., Harbeck, N., ... Pashayan, N. (2018). Epigenome-based cancer risk prediction: Rationale, opportunities and challenges. Nature Reviews Clinical Oncology, 15(5), 292-309. https://doi.org/10.1038/nrclinonc.2018.30