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@ARTICLE{Wankhede:302850,
      author       = {D. Wankhede$^*$ and N. Halama$^*$ and M. Kloor$^*$ and H.
                      Brenner$^*$ and M. Hoffmeister$^*$},
      title        = {{D}iabetes and {C}olorectal {C}ancer {R}isk and {S}urvival
                      {A}ccording to {T}umor {I}mmunity {S}tatus.},
      journal      = {Journal of clinical oncology},
      volume       = {43},
      number       = {26},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2025-01390},
      pages        = {2930-2941},
      year         = {2025},
      note         = {#EA:C070#LA:C070# / 2025 Sep 10;43(26):2930-2941 / vormals
                      D240},
      abstract     = {Type 2 diabetes (T2D) has been associated with an increased
                      risk of colorectal cancer (CRC) and poorer survival
                      outcomes. However, the role of tumor immune status in
                      influencing these relationships remains unclear.We conducted
                      a population-based matched case-control study (n = 4,724)
                      with prospective long-term follow-up of CRC cases (n =
                      2,321; median follow-up, 9.5 years). Tumor immune status was
                      assessed using an immune cell score (ICS), derived from CD3+
                      and CD8+ T-cell densities measured at the invasive margin
                      and tumor core of resected specimens. ICS was stratified
                      into high (ICSHi), intermediate (ICSInt), and low (ICSLow)
                      immune infiltration on the basis of standard cutoffs $(25\%$
                      and $70\%).$ Multivariable logistic regression estimated CRC
                      risk, whereas time-dependent Cox regression evaluated
                      survival outcomes. Primary end points included CRC-specific
                      survival and disease-free survival (DFS).The association
                      between T2D and CRC risk differed significantly by ICS (P
                      for heterogeneity = .02). T2D was associated with an
                      increased risk of CRC (odds ratio [OR], 1.39 $[95\%$ CI,
                      1.17 to 1.66]), particularly for ICSLow (OR, 1.80 $[95\%$
                      CI, 1.35 to 2.39]) and ICSInt subtypes (OR, 1.42 $[95\%$ CI,
                      1.17 to 1.66]), but not for ICSHi CRC subtype (OR, 1.16
                      $[95\%$ CI, 0.88 to 1.52]). Patients with T2D with ICSLow
                      tumors showed poorer CRC-specific survival (hazard ratio
                      [HR], 1.99 $[95\%$ CI, 1.30 to 3.05]) and DFS (HR, 1.53
                      $[95\%$ CI, 1.05 to 2.26]) than those without T2D, but not
                      for ICSInt and ICSHi CRC subtypes. Patients with T2D showed
                      inferior overall and non-cancer-related survival regardless
                      of immune subtypes.T2D disproportionately affects CRC risk
                      and survival in tumors with low immune infiltration,
                      suggesting a continuum of T2D's impact from tumorigenesis to
                      prognosis, through systemic and tumor-specific immune
                      modulation. These findings highlight the need for precision
                      prevention strategies integrating metabolic and immune-based
                      interventions to mitigate CRC burden in patients with T2D.},
      cin          = {C070 / D196 / D470 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)D196-20160331 /
                      I:(DE-He78)D470-20160331 / 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:40658916},
      doi          = {10.1200/JCO-25-00148},
      url          = {https://inrepo02.dkfz.de/record/302850},
}