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Lookup NU author(s): Professor Caroline Relton
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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. © 2014 American Association for Cancer Research.
Author(s): Chuang S-C, Fanidi A, Ueland PM, Relton C, Midttun O, Vollset SE, Gunter MJ, Seck MJ, Travis RC, Wareham N, Trichopoulou A, Lagiou P, Trichopoulos D, Peeters PHM, Bueno-De-Mesquita HB, Boeing H, Wientzek A, Kuehn T, Kaaks R, Tumino R, Agnoli C, Palli D, Naccarati A, Aicua EA, Sanchez MJ, Quiros JR, Chirlaque M-D, Agudo A, Johansson M, Grankvist K, Boutron-Ruault M-C, Clavel-Chapelon F, Fagherazzi G, Weiderpass E, Riboli E, Brennan PJ, Vineis P, Johansson M
Publication type: Article
Publication status: Published
Journal: Cancer Epidemiology Biomarkers and Prevention
Year: 2014
Volume: 23
Issue: 3
Pages: 461-468
Print publication date: 01/03/2014
Online publication date: 19/12/2013
Acceptance date: 04/11/2013
ISSN (print): 1055-9965
ISSN (electronic): 1538-7755
Publisher: American Association for Cancer Research Inc.
URL: https://doi.org/10.1158/1055-9965.EPI-13-0770
DOI: 10.1158/1055-9965.EPI-13-0770
PubMed id: 24357106
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