{
  "abstract": "Background High ultra-processed food (UPF) intake has been linked to colorectal cancer (CRC), but underlying mechanisms remain unclear.Objective To evaluate a metabolomic pattern of UPF intake and its association with CRC risk.Design Integrating food frequency questionnaire data and high-throughput metabolomic profiling in 1740 participants (mean age at blood draw: 59.9 years; >95% non-Hispanic white participants) from nested case-control studies within the Nurses’ Health Study and Health Professionals Follow-up Study, we derived and validated a UPF-related metabolomic pattern as a weighted sum of metabolites selected via elastic net regression with 10-fold cross-validation. We evaluated prospective associations of this pattern and individual metabolites with CRC risk using multivariable conditional logistic regression in 686 pairs of incident CRC cases and matched controls.Results Among 222 metabolites, we constructed a UPF metabolomic pattern comprising 50 metabolites, primarily lipids and amino acids, with 22 positively and 28 inversely associated with total UPF intake (pattern vs intake: Spearman rho=0.35). The pattern was associated with higher CRC risk (highest vs lowest quintile: OR (95% CI) 1.71 (1.15 to 2.53), p value trend=0.002). Correlations of individual metabolites with UPF intake were moderately aligned with their associations with CRC risk (rho=0.50). N2, N2-dimethylguanosine, a marker of meat/poultry intake, was positively associated with CRC risk (1.96 (1.27 to 3.03)), while 21-deoxycortisol, related to cortisol biosynthesis, was inversely associated (0.59 (0.41 to 0.86)).Conclusion We developed a UPF metabolomic pattern. The pattern and several metabolites were associated with CRC risk, providing biological insights into potential pathways underlying the UPF-CRC relationship.",
  "authors": [
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Clinical and Translational Epidemiology Unit, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Mengxi Du"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Xinyu Wang"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Dong Hang"
    },
    {
      "affiliations": [
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Fenglei Wang"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Yujia Lu"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Clinical and Translational Epidemiology Unit, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Kai Wang"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Alaina M Bever"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Ana Nogal"
    },
    {
      "affiliations": [
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Danielle Haslam"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA",
        "Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan",
        "Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA",
        "Harvard Chan Microbiome in Public Health Center, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Shuji Ogino"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"
      ],
      "name": "Jeffrey A Meyerhardt"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Liming Liang"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Qi Sun"
    },
    {
      "affiliations": [
        "Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA",
        "Harvard Chan Microbiome in Public Health Center, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Curtis Huttenhower"
    },
    {
      "affiliations": [
        "Clinical and Translational Epidemiology Unit, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA",
        "Harvard Chan Microbiome in Public Health Center, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Andrew T Chan"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Frank B Hu"
    },
    {
      "affiliations": [
        "Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Department of Nutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA",
        "Clinical and Translational Epidemiology Unit, Department of Medicine and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA",
        "Harvard Chan Microbiome in Public Health Center, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA"
      ],
      "name": "Mingyang Song"
    }
  ],
  "title": "Metabolomic pattern of ultraprocessed food intake and its association with colorectal cancer risk",
  "uid": "0a1f30c3-067b-5062-b508-55832642d40a"
}