• Joseph A Rothwell, Jelena Bešević, Niki Dimou, Marie Breeur, Neil Murphy, Mazda Jenab, Roland Wedekind, Vivian Viallon, Pietro Ferrari, David Achaintre, Audrey Gicquiau, Sabina Rinaldi, Augustin Scalbert, Inge Huybrechts, Cornelia Prehn, Jerzy Adamski, Amanda J Cross, Hector Keun, Marc Chadeau-Hyam, Marie-Christine Boutron-Ruault, Kim Overvad, Christina C Dahm, Therese Haugdahl Nøst, Torkjel M Sandanger, Guri Skeie, Raul Zamora-Ros, Kostas K Tsilidis, Fabian Eichelmann, Matthias B Schulze, Bethany van Guelpen, Linda Vidman, Maria-José Sánchez, Pilar Amiano, Eva Ardanaz, Karl Smith-Byrne, Ruth Travis, Verena Katzke, Rudolf Kaaks, Jeroen W G Derksen, Sandra Colorado-Yohar, Rosario Tumino, Bas Bueno-de-Mesquita, Paolo Vineis, Domenico Palli, Fabrizio Pasanisi, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, and Marc J Gunter.
• Centre for Epidemiology and Population Health (Inserm U1018), Exposome and Heredity team, Faculté de Médecine, Université Paris-Saclay, UVSQ, Gustave Roussy, F-94805, Villejuif, France. joseph.rothwell@inserm.fr.
• Bmc Med. 2023 Feb 28; 21 (1): 8080.

BackgroundAmino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.MethodsConcentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.ResultsHistidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.ConclusionsHigher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.© 2023. The Author(s).

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