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Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study

Widschwendter, M; Apostolidou, S; Raum, E; Rothenbacher, D; Fiegl, H; Menon, U; Stegmaier, C; ... Brenner, H; + view all (2008) Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study. PLOS ONE , 3 (7) , Article e2656. 10.1371/journal.pone.0002656. Green open access

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Abstract

Background: Epigenetic changes are emerging as one of the most important events in carcinogenesis. Two alterations in the pattern of DNA methylation in breast cancer (BC) have been previously reported; active estrogen receptor-a (ER-a) is associated with decreased methylation of ER-a target (ERT) genes, and polycomb group target (PCGT) genes are more likely than other genes to have promoter DNA hypermethylation in cancer. However, whether DNA methylation in normal unrelated cells is associated with BC risk and whether these imprints can be related to factors which can be modified by the environment, is unclear.Methodology/Principal Findings: Using quantitative methylation analysis in a case-control study (n = 1,083) we found that DNA methylation of peripheral blood cell DNA provides good prediction of BC risk. We also report that invasive ductal and invasive lobular BC is characterized by two different sets of genes, the latter particular by genes involved in the differentiation of the mesenchyme (PITX2, TITF1, GDNF and MYOD1). Finally we demonstrate that only ERT genes predict ER positive BC; lack of peripheral blood cell DNA methylation of ZNF217 predicted BC independent of age and family history (odds ratio 1.49; 95% confidence interval 1.12-1.97; P = 0.006) and was associated with ER-a bioactivity in the corresponding serum.Conclusion/Significance: This first large-scale epigenotyping study demonstrates that DNA methylation may serve as a link between the environment and the genome. Factors that can be modulated by the environment (like estrogens) leave an imprint in the DNA of cells that are unrelated to the target organ and indicate the predisposition to develop a cancer. Further research will need to demonstrate whether DNA methylation profiles will be able to serve as a new tool to predict the risk of developing chronic diseases with sufficient accuracy to guide preventive measures.

Type: Article
Title: Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0002656
Publisher version: http://dx.doi.org/10.1371/journal.pone.0002656
Language: English
Additional information: © 2008 Widschwendter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The work described in this manuscript was supported by The Eve Appeal and The Oak Foundation and grants from the European Union and the FWF Austrian Science Fund (awarded to M. Widschwendter) and by a grant from the Baden-Württemberg Ministry of Research, Science and Arts (awarded to H. Brenner). The funders did not play any role in the design or conduct of the study.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/141838
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