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@ARTICLE{Mandle:288812,
      author       = {H. B. Mandle and M. Jenab and M. J. Gunter and A.
                      Tjønneland and A. Olsen and C. C. Dahm and J. Zhang and
                      P.-E. Sugier and J. Rothwell and G. Severi and R. Kaaks$^*$
                      and V. A. Katzke$^*$ and M. B. Schulze and G. Masala and S.
                      Sieri and S. Panico and C. Sacerdote and C. Bonet and M.-J.
                      Sánchez and P. Amiano and J. M. Huerta and M. Guevara and
                      R. Palmqvist and T. Löwenmark and A. Perez-Cornago and E.
                      Weiderpass and A. K. Heath and A. J. Cross and P. Vineis and
                      D. J. Hughes and V. Fedirko},
      title        = {{I}nflammation and {G}ut {B}arrier {F}unction-{R}elated
                      {G}enes and {C}olorectal {C}ancer {R}isk in {W}estern
                      {E}uropean {P}opulations.},
      journal      = {Mutagenesis},
      volume       = {40},
      number       = {1},
      issn         = {0267-8357},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2024-00483},
      pages        = {48-60},
      year         = {2025},
      note         = {2025 Mar 15;40(1):48-60},
      abstract     = {Gut barrier dysfunction and related inflammation are known
                      to be associated with the development and progression of
                      colorectal cancer (CRC). We investigated associations of 292
                      single-nucleotide polymorphisms (SNPs) from 27 genes related
                      to endotoxins/lipopolysaccharide (LPS) sensing and
                      tolerance, mucin synthesis, inflammation, and Crohn's
                      disease with colon and rectal cancer risks. Incident CRC
                      cases (N=1,374; colon=871, rectum=503) were matched 1:1 to
                      controls nested within the European Prospective
                      Investigation into Cancer and Nutrition cohort. Previously
                      measured serum concentrations of gut barrier function and
                      inflammation biomarkers (flagellin/LPS-specific
                      immunoglobulins and C-reactive protein [CRP]) were available
                      for a sub-set of participants (Ncases=1,001; Ncontrols=667).
                      Forty-two unique SNPs from 19 different genes were
                      associated with serum biomarkers at Punadjusted≤0.05 among
                      controls. Among SNPs associated with a gut permeability
                      score, 24 SNPs were in genes related to LPS sensing and
                      mucin synthesis. Nine out of 12 SNPs associated with CRP
                      were in genes related to inflammation or Crohn's disease.
                      TLR4 was associated with colon cancer at the SNP level (nine
                      SNPs, all Punadjusted≤0.04) and at the gene level
                      (Punadjusted≤0.01). TLR4 rs10759934 was associated with
                      rectal cancer but not colon cancer. Similarly, IL10 was
                      associated with rectal cancer risk at a SNP and gene level
                      (both Punadjusted ≤ 0.01), but not colon cancer. Genes and
                      SNPs were selected a priori therefore we present unadjusted
                      P-values. However, no association was statistically
                      significant after multiple testing correction. This large
                      and comprehensive study has identified gut barrier function
                      and inflammation-related genes possibly contributing to CRC
                      risk in European populations and is consistent with
                      potential etiological links between host genetic background,
                      gut barrier permeability, microbial endotoxemia and CRC
                      development.},
      keywords     = {colorectal neoplasms (Other) / gut barrier (Other) /
                      incidence (Other) / inflammation (Other) / single nucleotide
                      polymorphism (SNP) (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38441165},
      doi          = {10.1093/mutage/geae008},
      url          = {https://inrepo02.dkfz.de/record/288812},
}