{
  "abstract": "Introduction Ultra-processed food (UPF) consumption has been associated with colorectal cancer risk, but the underlying biological mechanisms remain unclear. We investigated the associations between UPF consumption, metabolic signatures, and colorectal cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods UPF intake was assessed among 5,738 and 8,564 cancer-free EPIC participants with measurements of 129 circulating endogenous metabolites and 35 exogenous fatty acids using mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates) and gas chromatography. Multivariable linear regression identified metabolites and fatty acids associated with UPF consumption. Partial Least Squares regression was used to derive a composite metabolic score related to UPF intake. Metabolites associated with UPF consumption were then evaluated for their association with colorectal cancer in an independent nested case-control study including 1,557 colorectal cancer cases and matched controls using conditional logistic regression. The composite score was examined for its association with colorectal cancer risk and tested in mediation analyses.Results Higher UPF consumption was associated with lower levels of phosphatidylcholines, sphingomyelins, omega-3 fatty acids, and heptadecanoic acid, and higher levels of stearic acid, industrial trans fatty acid elaidic acid, and omega-6 polyunsaturated fatty acids. Phosphatidylcholines and sphingomyelins were inversely associated with colorectal cancer, whereas stearic acid showed a positive association. The metabolic signature score was positively associated with colorectal cancer risk (OR: 1.09, 95% CI: 1.00–1.17, p=0.041) and with rectal cancer risk in men (OR: 1.60, 95% CI: 1.10–2.32, p=0.013). These associations remained significant after adjustment for UPF consumption. UPF intake was associated with colorectal cancer risk in the overall EPIC cohort (HR: 1.06, 95% CI: 1.02–1.09, p=0.001), though not significantly in the nested case-control study. Mediation analysis suggested a small indirect effect of UPF consumption on colorectal cancer risk through metabolic signatures.Conclusions Higher UPF consumption was associated with specific metabolic changes, some of which were linked to colorectal cancer risk. These findings suggest potential metabolic pathways, and in particular inflammatory pathways, that could be involved in colorectal carcinogenesis, but further research is needed to confirm these associations.",
  "authors": [
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom",
        "Medical Research Council Centre for Environment and Health, Imperial College London, London, United Kingdom"
      ],
      "name": "Emine Koc Cakmak"
    },
    {
      "affiliations": [
        "Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France"
      ],
      "name": "Jessica Blanco-Lopez"
    },
    {
      "affiliations": [
        "Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France"
      ],
      "name": "Bernadette Chimera"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom"
      ],
      "name": "Marc Gunter"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom",
        "Medical Research Council Centre for Environment and Health, Imperial College London, London, United Kingdom"
      ],
      "name": "Oliver Robinson"
    },
    {
      "affiliations": [
        "Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France"
      ],
      "name": "Inge Huybrechts"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom",
        "Medical Research Council Centre for Environment and Health, Imperial College London, London, United Kingdom"
      ],
      "name": "Paolo Vineis"
    }
  ],
  "title": "O25 Ultra-processed food consumption, metabolic signatures, and colorectal cancer risk in a large European longitudinal study",
  "uid": "60376648-cd24-5487-aa1d-7adcddb04dd4"
}