1. Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.
- Author
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Rothwell, JA, Murphy, N, Bešević, J, Kliemann, N, Jenab, M, Ferrari, P, Achaintre, D, Gicquiau, A, Vozar, B, Scalbert, A, Huybrechts, I, Freisling, H, Prehn, C, Adamski, J, Cross, AJ, Pala, VM, Boutron-Ruault, M-C, Dahm, CC, Overvad, K, Gram, IT, Sandanger, TM, Skeie, G, Jakszyn, P, Tsilidis, KK, Aleksandrova, K, Schulze, MB, Hughes, DJ, van Guelpen, B, Bodén, S, Sánchez, M-J, Schmidt, JA, Katzke, V, Kühn, T, Colorado-Yohar, S, Tumino, R, Bueno-de-Mesquita, B, Vineis, P, Masala, G, Panico, S, Eriksen, AK, Tjønneland, A, Aune, D, Weiderpass, E, Severi, G, Chajès, V, Gunter, MJ, Rothwell, JA, Murphy, N, Bešević, J, Kliemann, N, Jenab, M, Ferrari, P, Achaintre, D, Gicquiau, A, Vozar, B, Scalbert, A, Huybrechts, I, Freisling, H, Prehn, C, Adamski, J, Cross, AJ, Pala, VM, Boutron-Ruault, M-C, Dahm, CC, Overvad, K, Gram, IT, Sandanger, TM, Skeie, G, Jakszyn, P, Tsilidis, KK, Aleksandrova, K, Schulze, MB, Hughes, DJ, van Guelpen, B, Bodén, S, Sánchez, M-J, Schmidt, JA, Katzke, V, Kühn, T, Colorado-Yohar, S, Tumino, R, Bueno-de-Mesquita, B, Vineis, P, Masala, G, Panico, S, Eriksen, AK, Tjønneland, A, Aune, D, Weiderpass, E, Severi, G, Chajès, V, and Gunter, MJ
- 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 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.
- Published
- 2022