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Cancer Epidemiol Biomarkers Prev. 2014 Mar;23(3):461-8. doi: 10.1158/1055-9965.EPI-13-0770. Epub 2013 Dec 19.

Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk.

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Authors' Affiliations: School of Public Health; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London; Institute for Ageing and Health, Newcastle University, Newcastle; Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; International Agency for Research on Cancer, Lyon; Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP); University Paris Sud, UMRS 1018; IGR, Villejuif, France; Section of Pharmacology, Institute of Medicine; Department of Public Health and Primary Health Care, University of Bergen; Laboratory of Clinical Biochemistry, Haukeland University Hospital; Bevital AS; Division of Epidemiology, Norwegian Institute of Public Health, Bergen; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School; Bureau of Epidemiologic Research, Academy of Athens; Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Cancer Registry and Histopathology Unit, "Civile M.P.Arezzo" Hospital, ASP Ragusa; Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Molecular and Nutritional Epidemiology Unit, Cancer Research an



Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer.


We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk.


Tryptophan (Ptrend = 2 × 10(-5)) and the kynurenine/tryptophan ratio (KTR; Ptrend = 4 × 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th vs. 1st) were 0.52 [95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR (Ptrend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, Ptrend = 3 × 10(-5)) that was only marginally affected by adjusting for methionine.


This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology.


This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.

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