Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 80 |
| Tidsskrift | BMC Medicine |
| Vol/bind | 21 |
| Udgave nummer | 1 |
| Antal sider | 13 |
| ISSN | 1741-7015 |
| DOI | |
| Status | Udgivet - 2023 |
| Eksternt udgivet | Ja |
Bibliografisk note
Funding Information:
The authors acknowledge funding from World Cancer Research Fund grant number 2014-02 and EC-BBMRI LPC (MG). RZ-R was supported by the “Miguel Servet” program (CPII20/00009) from the Institute of Health Carlos III (Co-funded by the European Social Fund (ESF) - ESF investing in your future).
Funding Information:
This work was conducted using the UK Biobank Resource (Application Number 25897) and the authors gratefully acknowledge the participants and those involved in building the resource. The authors thank all European Prospective Investigation into Cancer and Nutrition centers for provision of biological samples and participant data. The research was made possible using the data and samples provided by the International Agency for Research on Cancer Biobank. This paper is dedicated to the memory of our colleague Dr. Bas Bueno-de-Mesquita. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.
Publisher Copyright:
© 2023, The Author(s).
ID: 340060215