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

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 GramTorkjel M Sandanger, Guri Skeie, Paula Jakszyn, Kostas K Tsilidis, Krasimira Aleksandrova, Matthias B Schulze, 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, Anne Tjønneland, Dagfinn Aune, Elisabete Weiderpass, Gianluca Severi, Véronique Chajès, Marc J Gunter

Research output: Contribution to journalArticlepeer-review


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 (EPIC) 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 5,738 cancer-free EPIC participants with metabolomics data. Partial least squares regression was used to derive fatty acid and endogenous metabolite signatures of WCRF/AICR score in this group. In an independent set of 1,608 colorectal cancer cases and matched controls, odds ratios (OR) and 95% confidence intervals (CI) 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 elevated odd-chain fatty acids, serine, glycine and specific phosphatidylcholines. Signatures were more strongly inversely associated 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 to 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 healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

Original languageEnglish
JournalClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Early online date03 Dec 2020
Publication statusEarly online date - 03 Dec 2020
Externally publishedYes

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