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@ARTICLE{Schttker:127475,
      author       = {B. Schöttker$^*$ and Y. Zhang$^*$ and J. Heiss$^*$ and K.
                      Butterbach$^*$ and E. H. J. M. Jansen and M.
                      Bewerunge-Hudler$^*$ and K.-U. Saum$^*$ and B. Holleczek and
                      H. Brenner$^*$},
      title        = {{D}iscovery of a novel epigenetic cancer marker related to
                      the oxidative status of human blood.},
      journal      = {Genes, chromosomes $\&$ cancer},
      volume       = {54},
      number       = {9},
      issn         = {1045-2257},
      address      = {New York, NY},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-03498},
      pages        = {583 - 594},
      year         = {2015},
      abstract     = {Long-lasting oxidative stress exposure may lead to
                      relatively stable epigenetic modifications of the DNA in
                      order to activate anti-oxidative defence mechanisms.
                      Oxidative stress related DNA methylation may therefore be
                      associated (causally or as a by-product) with cancer. We
                      measured derivatives of reactive oxygen metabolites (D-ROM),
                      total thiol levels (TTL) and DNA methylation with the
                      Illumina Infinium 450K BeadChip in three samples of German
                      individuals aged ≥50 years: n = 1,000 ESTHER study
                      baseline participants (DNA methylation only), n = 99
                      ESTHER eight-year follow-up participants and n = 142
                      participants of the BLITZ study. The correlation coefficient
                      of methylation at cg10342304 and D-ROM in the ESTHER 8-year
                      follow-up sample (r = -0.427; P = 1 × 10(-5)) was
                      replicated with a P-value indicating statistical
                      significance after correction for multiple testing in the
                      BLITZ sample (r = -0.192; P = 0.022). The
                      association was robust to adjusting for potential
                      confounders. In the ESTHER baseline sample, the hazard ratio
                      for cancer development in 11 years of follow-up comparing
                      bottom and top quartile of DNA methylation at cg10342304 was
                      1.86 $(95\%-confidence-interval$ 1.01-3.43). In summary,
                      this first epigenome-wide screening and replication study
                      with oxidative status markers observed a negative
                      correlation of D-ROM levels and DNA methylation at
                      cg10342304 in two independent cohorts. This CpG site is
                      located in the body region of the nucleoredoxin gene. The
                      nucleoredoxin protein is a redox-dependent inhibitor of the
                      Wnt/ß-catenin signaling pathway, a well-characterized
                      cancer pathway. If the observed CpG-cancer association can
                      be successfully replicated by other studies, this epigenetic
                      marker could be an interesting biomarker of cancer risk.},
      keywords     = {Biomarkers, Tumor (NLM Chemicals) / Reactive Oxygen Species
                      (NLM Chemicals)},
      cin          = {C070 / W110 / G110},
      ddc          = {570},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)W110-20160331 /
                      I:(DE-He78)G110-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26173806},
      doi          = {10.1002/gcc.22271},
      url          = {https://inrepo02.dkfz.de/record/127475},
}