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Inflammation\u2010induced activation of the kynurenine pathway may play a role in cancer\u2010related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12\u2009months post\u2010treatment. Repeated measurements at 6\u2009weeks, 6\u2009months, and 12\u2009months post\u2010treatment were performed in 249 stage I\u2010III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography\u2010tandem mass spectrometry (LC\/MS\u2013MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder\u2010adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid\u2010to\u2010quinolinic acid ratio (KA\/QA), were associated with less fatigue and better functioning, while a higher kynurenine\u2010to\u2010tryptophan ratio (KTR) and 3\u2010hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA\/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12\u2009months post\u2010treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment.<\/jats:p>","DOI":"10.1002\/ijc.34992","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T04:38:32Z","timestamp":1716525512000},"page":"1172-1190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12\u2009months post\u2010treatment"],"prefix":"10.1002","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-6198","authenticated-orcid":false,"given":"Dani\u00eblle D. B.","family":"Holthuijsen","sequence":"first","affiliation":[{"name":"Department of Epidemiology, CARIM Cardiovascular Research Institute Maastricht University  Maastricht The Netherlands"},{"name":"Department of Epidemiology, GROW Research Institute for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"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 Research Institute for Oncology and Reproduction Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn J. 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