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@ARTICLE{Neumeyer:143280,
      author       = {S. M. Neumeyer$^*$ and O. Popanda$^*$ and D. Edelmann$^*$
                      and K. Butterbach$^*$ and C. Toth and W. Roth and H. Bläker
                      and R. Jiang$^*$ and E. Herpel and C. Jäkel$^*$ and P.
                      Schmezer$^*$ and L. Jansen$^*$ and E. Alwers$^*$ and A.
                      Benner$^*$ and B. Burwinkel$^*$ and M. Hoffmeister$^*$ and
                      H. Brenner$^*$ and J. Chang-Claude$^*$},
      title        = {{G}enome-wide {DNA} methylation differences according to
                      oestrogen receptor beta status in colorectal cancer.},
      journal      = {Epigenetics},
      volume       = {14},
      number       = {5},
      issn         = {1559-2308},
      address      = {Austin, Tex.},
      publisher    = {Landes Bioscience},
      reportid     = {DKFZ-2019-00878},
      pages        = {477-493},
      year         = {2019},
      abstract     = {Involvement of sex hormones in colorectal cancer (CRC)
                      development has been linked to oestrogen receptor β (ERβ).
                      Expression of ERβ is found reduced in tumour tissue and
                      inversely related to mortality. However, mechanisms are not
                      well understood. Our study aimed to detect differentially
                      methylated genes associated with ERβ expression, which
                      could point to mechanisms by which ERβ could influence risk
                      and prognosis of CRC. Epigenome-wide DNA methylation
                      profiling was performed using Illumina HumanMethylation450k
                      BeadChip arrays in two independent tumour sample sets of CRC
                      patients recruited in 2003-2010 by the German DACHS study
                      (discovery cohort n = 917, replication cohort n = 907).
                      ERβ expression was measured using immunohistochemistry and
                      scored as negative, moderate and high. Differentially
                      methylated CpG sites and genomic regions were determined
                      using limma in the R-package RnBeads. For the comparison of
                      tumours with moderate/high ERβ versus negative expression,
                      differentially methylated CpG sites were identified but not
                      confirmed by replication. Comparing tumours of high with
                      tumours of negative ERβ expression revealed 2,904
                      differentially methylated CpG sites of which 403 were
                      replicated (FDR adjusted p-value<0.05). Replicated CpGs were
                      annotated to genes such as CD36, HK1 or LRP5. A survival
                      analysis indicates that 30 of the replicated CpGs are also
                      associated with overall survival (FDR-adjusted
                      p-value<0.05). The regional analysis identified 60
                      differentially methylated promotor regions. The
                      epigenome-wide analysis identified both novel genes as well
                      as genes already implicated in CRC. Follow-up mechanistic
                      studies to better understand the regulatory role of ERβ
                      could inform potential targets for improving treatment or
                      prevention of CRC.},
      cin          = {C020 / B370 / C060 / C070 / L101 / L501},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331 / I:(DE-He78)B370-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)C070-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)L501-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30931802},
      doi          = {10.1080/15592294.2019.1595998},
      url          = {https://inrepo02.dkfz.de/record/143280},
}