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 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 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.
Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort / Rothwell, Joseph A; Murphy, Neil; Bešević, Jelena; Kliemann, Nathalie; Jenab, Mazda; Ferrari, Pietro; Achaintre, David; Gicquiau, Audrey; Vozar, Béatrice; Scalbert, Augustin; Huybrechts, Inge; Freisling, Heinz; Prehn, Cornelia; Adamski, Jerzy; Cross, Amanda J; Pala, Valeria Maria; Boutron-Ruault, Marie-Christine; Dahm, Christina C; Overvad, Kim; Gram, Inger Torhild; Sandanger, Torkjel M; Skeie, Guri; Jakszyn, Paula; Tsilidis, Kostas K; Aleksandrova, Krasimira; Schulze, Matthias B; Hughes, David J; van Guelpen, Bethany; Bodén, Stina; Sánchez, Maria-José; Schmidt, Julie A; Katzke, Verena; Kühn, Tilman; Colorado-Yohar, Sandra; Tumino, Rosario; Bueno-de-Mesquita, Bas; Vineis, Paolo; Masala, Giovanna; Panico, Salvatore; Eriksen, Anne Kirstine; Tjønneland, Anne; Aune, Dagfinn; Weiderpass, Elisabete; Severi, Gianluca; Chajès, Véronique; Gunter, Marc J. - In: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY. - ISSN 1542-3565. - ELETTRONICO. - (2020), pp. 0-0. [10.1016/j.cgh.2020.11.045]
Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort
Masala, Giovanna;Severi, Gianluca;
2020
Abstract
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 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 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.
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