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@ARTICLE{Papadimitriou:298365,
      author       = {N. Papadimitriou and N. Kazmi and K. K. Tsilidis and R. C.
                      Richmond and B. M. Lynch and B. Bendinelli and F. Ricceri
                      and M.-J. Sánchez and C. Trobajo-Sanmartín and P. Jakszyn
                      and V. Simeon and G. Severi and V. Perduca and T. Truong and
                      P. Ferrari and P. Keski-Rahkonen and E. Weiderpass and F.
                      Eichelmann and M. B. Schulze and V. Katzke$^*$ and R.
                      Turzanski-Fortner$^*$ and A. K. Heath and D. Aune and R.
                      Harewood and C. C. Dahm and A. Llorente and M. J. Gunter and
                      N. Murphy and S. J. Lewis},
      title        = {{I}dentifying metabolomic mediators of the physical
                      activity and colorectal cancer relationship.},
      journal      = {Cancer epidemiology, biomarkers $\&$ prevention},
      volume       = {34},
      number       = {4},
      issn         = {1055-9965},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-00263},
      pages        = {578-587},
      year         = {2025},
      note         = {2025 Apr 3;34(4):578-587},
      abstract     = {Current evidence suggests higher physical activity (PA)
                      levels are associated with a reduced risk of colorectal
                      cancer (CRC). However, the mediating role of the circulating
                      metabolome in this relationship remains unclear.Targeted
                      metabolomics data from 6,055 participants in the EPIC cohort
                      were used to identify metabolites associated with PA and
                      derive a metabolomic signature of PA levels. PA levels were
                      estimated using the validated Cambridge PA index based on
                      baseline questionnaires. Mediation analyses were conducted
                      in a nested case-control study (1,585 cases, 1,585 controls)
                      to examine whether individual metabolites and the
                      metabolomic signature mediated the PA-CRC association.PA was
                      inversely associated with CRC risk (odds ratio [OR] per
                      category change: 0.90, $95\%$ confidence intervals [CI]:
                      0.83, 0.97; p-value = 0.009). PA levels were associated with
                      24 circulating metabolites after false discovery rate
                      correction (FDR), with the strongest associations observed
                      for phosphatidylcholine acyl-alkyl (PC ae) C34:3
                      (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and
                      lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted
                      p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated
                      the PA-CRC association (natural indirect effect: 0.991,
                      $95\%$ CI: 0.982, 0.999; p-value = 0.04), explaining $7.4\%$
                      of the association. No mediation effects were observed for
                      the remaining metabolites or the overall PA metabolite
                      signature.PC ae C34:3 mediates part of the PA-CRC inverse
                      association, but further studies with improved PA measures
                      and extended metabolomic panels are needed.These findings
                      provide insights into PA-related biological mechanisms
                      influencing CRC risk and suggest potential targets for
                      cancer prevention interventions.},
      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:39883068},
      doi          = {10.1158/1055-9965.EPI-24-1390},
      url          = {https://inrepo02.dkfz.de/record/298365},
}