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@ARTICLE{Gibbs:154764,
      author       = {D. C. Gibbs and R. M. Bostick and M. McCullough and C. Um
                      and D. Flanders and M. Jenab and E. Weiderpass and B.
                      Gylling and I. T. Gram and A. K. Heath and S. Colorado-Yohar
                      and C. C. Dahm and B. Bueno-de-Mesquita and A. Perez-Cornago
                      and A. Trichopoulou and R. Tumino and T. Kühn$^*$ and V.
                      Fedirko},
      title        = {{A}ssociation of pre-diagnostic vitamin {D} status with
                      mortality among colorectal cancer patients differs by
                      common, inherited vitamin {D}-binding protein isoforms.},
      journal      = {International journal of cancer},
      volume       = {147},
      number       = {10},
      issn         = {1097-0215},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2020-01011},
      pages        = {2725-2734},
      year         = {2020},
      note         = {2020 Nov 15;147(10):2725-2734},
      abstract     = {Lower pre-diagnostic circulating 25-hydroxyvitamin D
                      (25[OH]D)-considered the best marker of total vitamin D
                      exposure-is associated with higher mortality risk among
                      colorectal cancer (CRC) patients. However, it is unknown
                      whether this association differs by the vitamin D-binding
                      protein (GC) isoform Gc2 (encoded by GC rs4588*C>A,
                      Thr436Lys), which may substantially affect vitamin D
                      metabolism and modify associations of 25(OH)D with
                      colorectal neoplasm risk. Pre-diagnostic 25(OH)D-mortality
                      associations according to Gc2 isoform were estimated using
                      multivariable Cox proportional hazards regression among
                      1,281 CRC cases (635 deaths, 483 from CRC) from two large
                      prospective cohorts conducted in the United States (Cancer
                      Prevention Study-II) and Europe (European Prospective
                      Investigation into Cancer and Nutrition). 25(OH)D
                      measurements were calibrated to a single assay, season
                      standardized, and categorized using Institute of Medicine
                      recommendations (deficient [<30], insufficient [30 - <50],
                      sufficient [≥50 nmol/L]). In the pooled analysis,
                      multivariable-adjusted hazard ratios (HRs) for CRC-specific
                      mortality associated with deficient relative to sufficient
                      25(OH)D concentrations were 2.24 $(95\%$ CI 1.44-3.49) among
                      cases with the Gc2 isoform, and 0.94 $(95\%$ CI 0.68-1.22)
                      among cases without Gc2 (Pinteraction = 0.0002). The
                      corresponding HRs for all-cause mortality were 1.80 $(95\%$
                      CI 1.24-2.60) among those with Gc2, and 1.12 $(95\%$ CI
                      0.84-1.51) among those without Gc2 (Pinteraction = 0.004).
                      Our findings suggest that the association of pre-diagnostic
                      vitamin D status with mortality among CRC patients may
                      differ by functional GC isoforms, and patients who inherit
                      the Gc2 isoform (GC rs4588*A) may particularly benefit from
                      higher circulating 25(OH)D for improved CRC prognosis.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32391587},
      doi          = {10.1002/ijc.33043},
      url          = {https://inrepo02.dkfz.de/record/154764},
}