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@ARTICLE{Bull:286383,
      author       = {C. Bull and E. Hazelwood and J. A. Bell and V. Tan and
                      A.-E. Constantinescu and C. Borges and D. Legge and K.
                      Burrows and J. R. Huyghe and H. Brenner$^*$ and S.
                      Castellvi-Bel and A. T. Chan and S.-S. Kweon and L. Le
                      Marchand and L. Li and I. Cheng and R. K. Pai and J. C.
                      Figueiredo and N. Murphy and M. J. Gunter and N. J. Timpson
                      and E. E. Vincent},
      title        = {{I}dentifying metabolic features of colorectal cancer
                      liability using {M}endelian randomization.},
      journal      = {eLife},
      volume       = {12},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DKFZ-2023-02786},
      pages        = {RP87894},
      year         = {2023},
      abstract     = {Recognizing the early signs of cancer risk is vital for
                      informing prevention, early detection, and survival.To
                      investigate whether changes in circulating metabolites
                      characterize the early stages of colorectal cancer (CRC)
                      development, we examined the associations between a genetic
                      risk score (GRS) associated with CRC liability (72
                      single-nucleotide polymorphisms) and 231 circulating
                      metabolites measured by nuclear magnetic resonance
                      spectroscopy in the Avon Longitudinal Study of Parents and
                      Children (N = 6221). Linear regression models were applied
                      to examine the associations between genetic liability to CRC
                      and circulating metabolites measured in the same individuals
                      at age 8 y, 16 y, 18 y, and 25 y.The GRS for CRC was
                      associated with up to $28\%$ of the circulating metabolites
                      at FDR-P < 0.05 across all time points, particularly with
                      higher fatty acids and very-low- and low-density lipoprotein
                      subclass lipids. Two-sample reverse Mendelian randomization
                      (MR) analyses investigating CRC liability (52,775 cases,
                      45,940 controls) and metabolites measured in a random subset
                      of UK Biobank participants (N = 118,466, median age 58 y)
                      revealed broadly consistent effect estimates with the GRS
                      analysis. In conventional (forward) MR analyses, genetically
                      predicted polyunsaturated fatty acid concentrations were
                      most strongly associated with higher CRC risk.These analyses
                      suggest that higher genetic liability to CRC can cause early
                      alterations in systemic metabolism and suggest that fatty
                      acids may play an important role in CRC development.This
                      work was supported by the Elizabeth Blackwell Institute for
                      Health Research, University of Bristol, the Wellcome Trust,
                      the Medical Research Council, Diabetes UK, the University of
                      Bristol NIHR Biomedical Research Centre, and Cancer Research
                      UK. The funders had no role in study design, data collection
                      and analysis, decision to publish, or preparation of the
                      manuscript. This work used the computational facilities of
                      the Advanced Computing Research Centre, University of
                      Bristol - http://www.bristol.ac.uk/acrc/.},
      keywords     = {Mendelian randomization (Other) / cancer biology (Other) /
                      colorectal cancer (Other) / epidemiology (Other) / global
                      health (Other) / human (Other) / metabolomics (Other) /
                      obesity (Other)},
      cin          = {C070 / C120 / HD01},
      ddc          = {600},
      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:38127078},
      doi          = {10.7554/eLife.87894},
      url          = {https://inrepo02.dkfz.de/record/286383},
}