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Rothwell, J.A.* ; Bešević, J.* ; Dimou, N.* ; Breeur, M.* ; Murphy, N.* ; Jenab, M.* ; Wedekind, R.* ; Viallon, V.* ; Ferrari, P.* ; Achaintre, D.* ; Gicquiau, A.* ; Rinaldi, S.* ; Scalbert, A.* ; Huybrechts, I.* ; Prehn, C. ; Adamski, J. ; Cross, A.J.* ; Keun, H.* ; Chadeau-Hyam, M.* ; Boutron-Ruault, M.C.* ; Overvad, K.* ; Dahm, C.C.* ; Nøst, T.H.* ; Sandanger, T.M.* ; Skeie, G.* ; Zamora-Ros, R.* ; Tsilidis, K.K.* ; Eichelmann, F.* ; Schulze, M.B.* ; van Guelpen, B.* ; Vidman, L.* ; Sánchez, M.J.* ; Amiano, P.* ; Ardanaz, E.* ; Smith-Byrne, K.* ; Travis, R.* ; Katzke, V.* ; Kaaks, R.* ; Derksen, J.W.G.* ; Colorado-Yohar, S.* ; Tumino, R.* ; Bueno-de-Mesquita, B.* ; Vineis, P.* ; Palli, D.* ; Pasanisi, F.* ; Eriksen, A.K.* ; Tjønneland, A.* ; Severi, G.* ; Gunter, M.J.*

Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts.

BMC Med. 21:80 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Amino 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. METHODS: Concentrations 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. RESULTS: Histidine 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. CONCLUSIONS: Higher 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Amino Acids ; Colorectal Cancer ; Glutamine ; Histidine; Histamine; Metaanalysis; Metabolism
ISSN (print) / ISBN 1741-7015
e-ISSN 1741-7015
Journal BMC Medicine
Quellenangaben Volume: 21, Issue: 1, Pages: , Article Number: 80 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)