Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies

Nikos Papadimitriou, Marc J. Gunter, Neil Murphy, Audrey Gicquiau, David Achaintre, Stefanie Brezina, Tanja Gumpenberger, Andreas Baierl, Jennifer Ose, Anne J.M.R. Geijsen, Eline H. van Roekel, Andrea Gsur, Biljana Gigic, Nina Habermann, Cornelia M. Ulrich, Ellen Kampman, Matty P. Weijenberg, Per Magne Ueland, Rudolf Kaaks, Verena KatzkeVittorio Krogh, Bas Bueno-de-Mesquita, Eva Ardanaz, Ruth C. Travis, Matthias B. Schulze, Maria José Sánchez, Sandra M. Colorado-Yohar, Elisabete Weiderpass, Augustin Scalbert, Pekka Keski-Rahkonen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.

Original languageEnglish
Pages (from-to)1659-1669
JournalInternational Journal of Cancer
Volume149
Issue number9
Early online date1 Jul 2021
DOIs
Publication statusPublished - 2021

Keywords

  • colon cancer
  • kynurenine
  • plasma
  • serotonin
  • tryptophan

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