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@ARTICLE{Gao:142933,
      author       = {X. Gao$^*$ and Y. Zhang$^*$ and B. Burwinkel$^*$ and Y.
                      Xuan$^*$ and B. Holleczek and H. Brenner$^*$ and B.
                      Schöttker$^*$},
      title        = {{T}he associations of {DNA} methylation alterations in
                      oxidative stress-related genes with cancer incidence and
                      mortality outcomes: a population-based cohort study.},
      journal      = {Clinical epigenetics},
      volume       = {11},
      number       = {1},
      issn         = {1868-7083},
      address      = {[S.l.]},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2019-00561},
      pages        = {14},
      year         = {2019},
      abstract     = {Reactive oxygen species may be involved in epigenetic gene
                      activation or silencing. We aimed to identify CpG sites, at
                      which DNA methylation is related to urinary 8-isoprostane
                      levels (biomarker of lipid peroxidation) and cancer or
                      mortality outcomes. This investigation was based on a
                      German, population-based cohort with linkage to cancer and
                      mortality registry data (2000-2016).Blood DNA methylation in
                      promoter regions of 519 genes, known to be involved in
                      pathways from oxidative stress (OS) to cancer, was obtained
                      at the cohort's baseline examination. Inverse associations
                      of DNA methylation at cg25365794 (ALOXE3) and cg08862778
                      (MTOR) with 8-isoprostane levels were observed in a
                      derivation set (n = 1000) and validated in two
                      independent subsets of the cohort (n = 548 and
                      n = 741). Multivariate regression models were used to
                      evaluate the associations of DNA methylation at the two CpG
                      sites with lung, colorectal, prostate, breast, and overall
                      cancer incidence as well as CVD, cancer, and all-cause
                      mortality. DNA methylation at cg25365794 (ALOXE3) was
                      inversely associated with lung and prostate cancer
                      incidence. DNA methylation at cg08862778 (MTOR) was
                      associated with a $43\%$ lower breast cancer incidence in
                      the top vs. bottom tertile.The finding for ALOXE3 may not be
                      causal. As ALOXE3 is mainly expressed in skin tissue, the
                      observed association might reflect the fact that both DNA
                      methylation at the ALOXE3 gene and urinary 8-isoprostane
                      concentrations depend on the level of OS in tissues.
                      Contrarily, the finding for the MTOR gene and breast cancer
                      is biologically plausible because the MTOR protein plays an
                      important role in PI3K/Akt signaling, which is a pathway
                      related to cancer development and cell senescence.},
      cin          = {C070 / C120 / C080 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)C080-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30678711},
      pmc          = {pmc:PMC6346508},
      doi          = {10.1186/s13148-018-0604-y},
      url          = {https://inrepo02.dkfz.de/record/142933},
}