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@ARTICLE{Constantinescu:278422,
      author       = {A.-E. Constantinescu and C. J. Bull and N. Jones and R.
                      Mitchell and K. Burrows and N. Dimou and S. Bézieau and H.
                      Brenner$^*$ and D. D. Buchanan and M. D'Amato and M. A.
                      Jenkins and V. Moreno and R. K. Pai and C. Y. Um and E.
                      White and N. Murphy and M. Gunter and N. J. Timpson and J.
                      R. Huyghe and E. E. Vincent},
      title        = {{C}irculating white blood cell traits and colorectal cancer
                      risk: {A} {M}endelian randomisation study.},
      journal      = {International journal of cancer},
      volume       = {154},
      number       = {1},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2023-01656},
      pages        = {94-103},
      year         = {2024},
      note         = {2024 Jan 1;154(1):94-103},
      abstract     = {Observational studies have suggested a protective role for
                      eosinophils in colorectal cancer (CRC) development and
                      implicated neutrophils, but the causal relationships remain
                      unclear. Here, we aimed to estimate the causal effect of
                      circulating white blood cell (WBC) counts (N = ~550 000) for
                      basophils, eosinophils, monocytes, lymphocytes and
                      neutrophils on CRC risk (N = 52 775 cases and 45 940
                      controls) using Mendelian randomisation (MR). For
                      comparison, we also examined this relationship using
                      individual-level data from UK Biobank (4043 incident CRC
                      cases and 332 773 controls) in a longitudinal cohort
                      analysis. The inverse-variance weighted (IVW) MR analysis
                      suggested a protective effect of increased basophil count
                      and eosinophil count on CRC risk [OR per 1-SD increase:
                      0.88, $95\%$ CI: 0.78-0.99, P = .04; OR: 0.93, $95\%$ CI:
                      0.88-0.98, P = .01]. The protective effect of eosinophils
                      remained [OR per 1-SD increase: 0.88, $95\%$ CI: 0.80-0.97,
                      P = .01] following adjustments for all other WBC subtypes,
                      to account for genetic correlation between the traits, using
                      multivariable MR. A protective effect of increased
                      lymphocyte count on CRC risk was also found [OR: 0.84,
                      $95\%$ CI: 0.76-0.93, P = 6.70e-4] following adjustment.
                      Consistent with MR results, a protective effect for
                      eosinophils in the cohort analysis in the fully adjusted
                      model [RR per 1-SD increase: 0.96, $95\%$ CI: 0.93-0.99, P =
                      .02] and following adjustment for the other WBC subtypes
                      [RR: 0.96, $95\%$ CI: 0.93-0.99, P = .001] was observed. Our
                      study implicates peripheral blood immune cells, in
                      particular eosinophils and lymphocytes, in CRC development,
                      highlighting a need for mechanistic studies to interrogate
                      these relationships.},
      keywords     = {Mendelian randomisation (Other) / UK biobank (Other) /
                      White blood cell count (Other) / colorectal cancer (Other) /
                      eosinophils (Other)},
      cin          = {C070 / C120 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37578112},
      doi          = {10.1002/ijc.34691},
      url          = {https://inrepo02.dkfz.de/record/278422},
}