TY - JOUR
T1 - Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk
AU - Chuang, Shu Chun
AU - Fanidi, Anouar
AU - Ueland, Per Magne
AU - Relton, Caroline
AU - Midttun, Oivind
AU - Vollset, Stein Emil
AU - Gunter, Marc J.
AU - Seck, Michael J.
AU - Travis, Ruth C.
AU - Wareham, Nicholas
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Peeters, Petra H.M.
AU - Bueno-De-Mesquita, H. Bas
AU - Boeing, Heiner
AU - Wientzek, Angelika
AU - Kuehn, Tilman
AU - Kaaks, Rudolf
AU - Tumino, Rosario
AU - Agnoli, Claudia
AU - Palli, Domenico
AU - Naccarati, Alessio
AU - Aicua, Eva Ardanaz
AU - Sanchez, María Jose
AU - Quiros, Jose Ramon
AU - Chirlaque, María Dolores
AU - Agudo, Antonio
AU - Johansson, Mikael
AU - Grankvist, Kjell
AU - Boutron-Ruault, Marie Christine
AU - Clavel-Chapelon, Francoise
AU - Fagherazzi, Guy
AU - Weiderpass, Elisabete
AU - Riboli, Elio
AU - Brennan, Paul J.
AU - Vineis, Paolo
AU - Johansson, Mattias
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896506651&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-13-0770
DO - 10.1158/1055-9965.EPI-13-0770
M3 - Article
C2 - 24357106
AN - SCOPUS:84896506651
SN - 1055-9965
VL - 23
SP - 461
EP - 468
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 3
ER -