Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study.
<h4>Background</h4>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-alpha (ER-alpha) is associated with decreased methylat...
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2008
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oai:doaj.org-article:f98b68ae969e4058864bfe51b49ad4072021-11-25T06:11:35ZEpigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study.1932-620310.1371/journal.pone.0002656https://doaj.org/article/f98b68ae969e4058864bfe51b49ad4072008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18628976/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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-alpha (ER-alpha) is associated with decreased methylation of ER-alpha 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.<h4>Methodology/principal findings</h4>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-alpha bioactivity in the corresponding serum.<h4>Conclusion/significance</h4>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.Martin WidschwendterSophia ApostolidouElke RaumDietrich RothenbacherHeidi FieglUsha MenonChrista StegmaierIan J JacobsHermann BrennerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 7, p e2656 (2008) |
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Medicine R Science Q Martin Widschwendter Sophia Apostolidou Elke Raum Dietrich Rothenbacher Heidi Fiegl Usha Menon Christa Stegmaier Ian J Jacobs Hermann Brenner Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| description |
<h4>Background</h4>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-alpha (ER-alpha) is associated with decreased methylation of ER-alpha 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.<h4>Methodology/principal findings</h4>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-alpha bioactivity in the corresponding serum.<h4>Conclusion/significance</h4>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. |
| format |
article |
| author |
Martin Widschwendter Sophia Apostolidou Elke Raum Dietrich Rothenbacher Heidi Fiegl Usha Menon Christa Stegmaier Ian J Jacobs Hermann Brenner |
| author_facet |
Martin Widschwendter Sophia Apostolidou Elke Raum Dietrich Rothenbacher Heidi Fiegl Usha Menon Christa Stegmaier Ian J Jacobs Hermann Brenner |
| author_sort |
Martin Widschwendter |
| title |
Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| title_short |
Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| title_full |
Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| title_fullStr |
Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| title_full_unstemmed |
Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. |
| title_sort |
epigenotyping in peripheral blood cell dna and breast cancer risk: a proof of principle study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/f98b68ae969e4058864bfe51b49ad407 |
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