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Therefore, we investigated associations between circulating concentrations of tryptophan\u2013kynurenine pathway metabolites and all\u2010cause mortality among CRC patients. This study utilizes data from 2102 stage I\u2013III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3\u2010hydroxykynurenine (HK), xanthurenic acid (XA), 3\u2010hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography\u2013tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above\u2010mentioned metabolites with all\u2010cause mortality, adjusted for potential confounders. During a median follow\u2010up of 3.2\u2009years (interquartile range: 2.2\u20134.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all\u2010cause mortality (per doubling in concentrations: tryptophan: HR\u2009=\u20090.56; 95%CI:0.41,0.76, XA: HR\u2009=\u20090.74; 95%CI:0.64,0.85, PA: HR\u2009=\u20090.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR\u2009=\u20091.80; 95%CI:1.47,2.21, QA: HR\u2009=\u20091.31; 95%CI:1.05,1.63). A higher kynurenine\u2010to\u2010tryptophan ratio, a marker of cell\u2010mediated immune activation, was associated with an increased risk of death (per doubling: HR\u2009=\u20092.07; 95%CI:1.52,2.83). In conclusion, tryptophan\u2013kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.<\/jats:p>","DOI":"10.1002\/ijc.35183","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T05:19:14Z","timestamp":1727068754000},"page":"552-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Circulating tryptophan\u2013kynurenine pathway metabolites are associated with all\u2010cause mortality among patients with stage I\u2013III colorectal cancer"],"prefix":"10.1002","volume":"156","author":[{"given":"Victoria","family":"Damerell","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Klaassen\u2010Dekker","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University &amp; Research  Wageningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Brezina","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"},{"name":"Department III: Media, Information and Design University of Applied Sciences and Arts, Hochschule Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arve","family":"Ulvik","sequence":"additional","affiliation":[{"name":"BEVITAL  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-2029","authenticated-orcid":false,"given":"Eline H.","family":"van Roekel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, GROW School for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreana N.","family":"Holowatyj","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"},{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"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"}]},{"given":"J\u00fcrgen","family":"B\u00f6hm","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":"Martijn J. 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