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. 2023 Feb 28;21(1):80.
doi: 10.1186/s12916-023-02739-4.

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

Joseph A Rothwell #  1 , Jelena Bešević #  2 , Niki Dimou  3 , Marie Breeur  3 , Neil Murphy  3 , Mazda Jenab  3 , Roland Wedekind  3 , Vivian Viallon  3 , Pietro Ferrari  3 , David Achaintre  3 , Audrey Gicquiau  3 , Sabina Rinaldi  3 , Augustin Scalbert  3 , Inge Huybrechts  3 , Cornelia Prehn  4 , Jerzy Adamski  5   6   7 , Amanda J Cross  8 , Hector Keun  9 , Marc Chadeau-Hyam  8 , Marie-Christine Boutron-Ruault  10 , Kim Overvad  11 , Christina C Dahm  11 , Therese Haugdahl Nøst  12 , Torkjel M Sandanger  12 , Guri Skeie  12 , Raul Zamora-Ros  13 , Kostas K Tsilidis  8   14 , Fabian Eichelmann  15   16 , Matthias B Schulze  16   17 , Bethany van Guelpen  18   19 , Linda Vidman  18 , Maria-José Sánchez  20   21   22   23 , Pilar Amiano  24   25   26 , Eva Ardanaz  22   27   28 , Karl Smith-Byrne  2   3 , Ruth Travis  2 , Verena Katzke  29 , Rudolf Kaaks  29 , Jeroen W G Derksen  30 , Sandra Colorado-Yohar  22   31   32 , Rosario Tumino  33 , Bas Bueno-de-Mesquita  34 , Paolo Vineis  8   35 , Domenico Palli  36 , Fabrizio Pasanisi  37 , Anne Kirstine Eriksen  38   39 , Anne Tjønneland  38 , Gianluca Severi  10   40 , Marc J Gunter  3   8
Affiliations

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

Joseph A Rothwell et al. BMC Med. .

Abstract

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.

Keywords: Amino acids; Colorectal cancer; Glutamine; Histidine.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart showing discovery and replication study design. CRC, colorectal cancer; EPIC, European Prospective Investigation into Nutrition and Cancer
Fig. 2
Fig. 2
Blood concentrations of amino acids as determined in fasted EPIC participants on the p150 or p180 Biocrates platform. Based on 654 and 354 cancer-free controls for p150 and p180 platforms, respectively
Fig. 3
Fig. 3
Fasting amino acid concentrations and their intercorrelations in EPIC cancer-free controls. Compounds are ordered by the hierarchical cluster as determined by Ward’s method. Squares represent groups of highly correlated compounds
See this image and copyright information in PMC

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