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

Shu Chun Chuang, Anouar Fanidi, Per Magne Ueland, Caroline Relton, Oivind Midttun, Stein Emil Vollset, Marc J. Gunter, Michael J. Seck, Ruth C. Travis, Nicholas Wareham, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Petra H.M. Peeters, H. Bas Bueno-De-Mesquita, Heiner Boeing, Angelika Wientzek, Tilman Kuehn, Rudolf Kaaks, Rosario TuminoClaudia Agnoli, Domenico Palli, Alessio Naccarati, Eva Ardanaz Aicua, María Jose Sanchez, Jose Ramon Quiros, María Dolores Chirlaque, Antonio Agudo, Mikael Johansson, Kjell Grankvist, Marie Christine Boutron-Ruault, Francoise Clavel-Chapelon, Guy Fagherazzi, Elisabete Weiderpass, Elio Riboli, Paul J. Brennan, Paolo Vineis, Mattias Johansson

Research output: Contribution to journalArticleResearchpeer-review

65 Citations (Scopus)


Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer andNutrition (EPIC) that included 893 incident lung cancer cases and 1,748matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: 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 fromprevious 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. Conclusions: 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. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number3
Publication statusPublished - Mar 2014
Externally publishedYes


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