Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort

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  • Metabolic

    Final published version, 1.65 MB, PDF document

  • Joseph A. Rothwell
  • Neil Murphy
  • Jelena Bešević
  • Nathalie Kliemann
  • Mazda Jenab
  • Pietro Ferrari
  • David Achaintre
  • Audrey Gicquiau
  • Béatrice Vozar
  • Augustin Scalbert
  • Inge Huybrechts
  • Heinz Freisling
  • Cornelia Prehn
  • Jerzy Adamski
  • Amanda J. Cross
  • Valeria Maria Pala
  • Marie Christine Boutron-Ruault
  • Christina C. Dahm
  • Kim Overvad
  • Inger Torhild Gram
  • Torkjel M. Sandanger
  • Guri Skeie
  • Paula Jakszyn
  • Kostas K. Tsilidis
  • Krasimira Aleksandrova
  • Matthias B. Schulze
  • David J. Hughes
  • Bethany van Guelpen
  • Stina Bodén
  • Maria José Sánchez
  • Julie A. Schmidt
  • Verena Katzke
  • Tilman Kühn
  • Sandra Colorado-Yohar
  • Rosario Tumino
  • Bas Bueno-de-Mesquita
  • Paolo Vineis
  • Giovanna Masala
  • Salvatore Panico
  • Anne Kirstine Eriksen
  • Dagfinn Aune
  • Elisabete Weiderpass
  • Gianluca Severi
  • Véronique Chajès
  • Marc J. Gunter

Background & Aims: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. Methods: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1–5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. Results: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29–0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50–0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86–1.00) overall. Signature associations were stronger in male compared with female participants. Conclusions: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

Original languageEnglish
JournalClinical Gastroenterology and Hepatology
Volume20
Issue number5
Pages (from-to)e1061-e1082
Number of pages20
ISSN1542-3565
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2020 AGA Institute

    Research areas

  • Colorectal Neoplasm, Risk Factors, Targeted Metabolomics, World Cancer Research Fund/American Institute for Cancer Research Recommendations

ID: 286487625