TY - JOUR
T1 - Epigenome-based cancer risk prediction
T2 - Rationale, opportunities and challenges
AU - Widschwendter, Martin
AU - Jones, Allison
AU - Evans, Iona
AU - Reisel, Daniel
AU - Dillner, Joakim
AU - Sundström, Karin
AU - Steyerberg, Ewout W.
AU - Vergouwe, Yvonne
AU - Wegwarth, Odette
AU - Rebitschek, Felix G.
AU - Siebert, Uwe
AU - Sroczynski, Gaby
AU - De Beaufort, Inez D.
AU - Bolt, Ineke
AU - Cibula, David
AU - Zikan, Michal
AU - Bjørge, Line
AU - Colombo, Nicoletta
AU - Harbeck, Nadia
AU - Dudbridge, Frank
AU - Tasse, Anne Marie
AU - Knoppers, Bartha M.
AU - Joly, Yann
AU - Teschendorff, Andrew E.
AU - Pashayan, Nora
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045578014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045578014&partnerID=8YFLogxK
U2 - 10.1038/nrclinonc.2018.30
DO - 10.1038/nrclinonc.2018.30
M3 - Review article
AN - SCOPUS:85045578014
VL - 15
SP - 292
EP - 309
JO - Nature Reviews Clinical Oncology
JF - Nature Reviews Clinical Oncology
SN - 1759-4774
IS - 5
ER -