Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. Export

@article{citeulike:6071608, 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-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. 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-alpha 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.}, author = {Widschwendter, Martin and Apostolidou, Sophia and Raum, Elke and Rothenbacher, Dietrich and Fiegl, Heidi and Menon, Usha and Stegmaier, Christa and Jacobs, Ian J. and Brenner, Hermann}, citeulike-article-id = {6071608}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0002656}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18628976}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18628976}, doi = {10.1371/journal.pone.0002656}, issn = {1932-6203}, journal = {PloS one}, keywords = {association, breast, epigenetics, gene\_specific\_methylation, hr, methylation, peripheral\_blood, polycomb}, number = {7}, posted-at = {2009-11-04 21:44:12}, priority = {2}, title = {Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study.}, url = {http://dx.doi.org/10.1371/journal.pone.0002656}, volume = {3}, year = {2008} }

TY - JOUR ID - citeulike:6071608 L3 - citeulike-article-id:6071608 N2 - 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-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. 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-alpha 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. IS - 7 JF - PloS one SN - 1932-6203 TI - Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. VL - 3 KW - association KW - breast KW - epigenetics KW - gene_specific_methylation KW - hr KW - methylation KW - peripheral_blood KW - polycomb AU - Widschwendter, Martin AU - Apostolidou, Sophia AU - Raum, Elke AU - Rothenbacher, Dietrich AU - Fiegl, Heidi AU - Menon, Usha AU - Stegmaier, Christa AU - Jacobs, Ian AU - Brenner, Hermann PY - 2008/// UR - http://dx.doi.org/10.1371/journal.pone.0002656 ER -