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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\u2010control 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\u2010SD\u00a0=\u00a00.44; 95% CI, 0.31\u20100.64) and EPIC (OR per 1\u2010SD\u00a0=\u00a00.86; 95%\u00a0CI, 0.74\u20100.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR\u00a0=\u00a06.39; 95%\u00a0CI, 3.61\u201011.3) and EPIC (OR\u00a0=\u00a02.03; 95%\u00a0CI, 1.20\u20103.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1\u2010SD\u00a0=\u00a00.74; 95%\u00a0CI, 0.55\u20100.98), positively associated in CORSA (OR per 1\u2010SD\u00a0=\u00a01.79; 95%\u00a0CI, 1.27\u20102.52), while no association was observed in EPIC. The kynurenine\u2010to\u2010tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1\u2010SD\u00a0=\u00a01.38; 95%\u00a0CI, 1.03\u20101.84) and CORSA (OR per 1\u2010SD\u00a0=\u00a01.44; 95%\u00a0CI, 1.06\u20101.96), 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\u2010to\u2010tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.<\/jats:p>","DOI":"10.1002\/ijc.33725","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T04:20:35Z","timestamp":1625199635000},"page":"1659-1669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Circulating tryptophan metabolites and risk of colon cancer: Results from case\u2010control and prospective cohort studies"],"prefix":"10.1002","volume":"149","author":[{"given":"Nikos","family":"Papadimitriou","sequence":"first","affiliation":[{"name":"International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Gunter","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-8249","authenticated-orcid":false,"given":"Neil","family":"Murphy","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Gicquiau","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Achaintre","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Brezina","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Gumpenberger","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Baierl","sequence":"additional","affiliation":[{"name":"Department of Statistics and Operations Research University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-9676","authenticated-orcid":false,"given":"Jennifer","family":"Ose","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute  Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne J. 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