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 Seckl; 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 Tumino; Claudia Agnoli; Domenico Palli; Alessio Naccarati; Eva Ardanaz Aicua; María-José Sánchez; José Ramón Quirós; María-Dolores Chirlaque; Antonio Agudo; Mikael Johansson; Kjell Grankvist; Marie-Christine Boutron-Ruault; Françoise Clavel-Chapelon; Guy Fagherazzi; Elisabete Weiderpass; Elio Riboli; Paul J Brennan; Paolo Vineis; Mattias Johansson

doi:10.1158/1055-9965.EPI-13-0770

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 Seckl, 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-José Sánchez, José Ramón Quirós, María-Dolores Chirlaque, Antonio Agudo, Mikael Johansson, Kjell Grankvist, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Guy Fagherazzi, Elisabete Weiderpass, Elio Riboli, Paul J Brennan, Paolo Vineis, Mattias Johansson

Research output: Contribution to journal › Article (Academic Journal) › peer-review

67 Citations (Scopus)

Abstract

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 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.

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 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.

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 language	English
Pages (from-to)	461-8
Number of pages	8
Journal	Cancer Epidemiology, Biomarkers and Prevention
Volume	23
Issue number	3
DOIs	https://doi.org/10.1158/1055-9965.EPI-13-0770
Publication status	Published - Mar 2014

Bibliographical note

Keywords

Adult
Aged
Case-Control Studies
Cohort Studies
Europe
Female
Humans
Kynurenine
Lung Neoplasms
Male
Middle Aged
Prospective Studies
Questionnaires
Risk Factors
Tryptophan
Tumor Markers, Biological

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1158/1055-9965.EPI-13-0770

Handle.net

Persistent link

MRC UoB UNITE Unit - Programme 2
Relton, C. L. (Principal Investigator) & Relton, C. L. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

Cite this

Chuang, S.-C., Fanidi, A., Ueland, P. M., Relton, C., Midttun, O., Vollset, S. E., Gunter, M. J., Seckl, M. J., Travis, R. C., Wareham, N., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Peeters, P. H. M., Bueno-de-Mesquita, H. B., Boeing, H., Wientzek, A., Kuehn, T., Kaaks, R., ... Johansson, M. (2014). Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk. Cancer Epidemiology, Biomarkers and Prevention, 23(3), 461-8. https://doi.org/10.1158/1055-9965.EPI-13-0770

@article{60702709bb3641d1a0cde3b6dbeea5ed,

title = "Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk",

abstract = "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 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.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 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.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.",

keywords = "Adult, Aged, Case-Control Studies, Cohort Studies, Europe, Female, Humans, Kynurenine, Lung Neoplasms, Male, Middle Aged, Prospective Studies, Questionnaires, Risk Factors, Tryptophan, Tumor Markers, Biological",

author = "Shu-Chun Chuang and Anouar Fanidi and Ueland, {Per Magne} and Caroline Relton and Oivind Midttun and Vollset, {Stein Emil} and Gunter, {Marc J} and Seckl, {Michael J} and Travis, {Ruth C} and Nicholas Wareham and Antonia Trichopoulou and Pagona Lagiou and Dimitrios Trichopoulos and Peeters, {Petra H M} and Bueno-de-Mesquita, {H Bas} and Heiner Boeing and Angelika Wientzek and Tilman Kuehn and Rudolf Kaaks and Rosario Tumino and Claudia Agnoli and Domenico Palli and Alessio Naccarati and Aicua, {Eva Ardanaz} and Mar{\'i}a-Jos{\'e} S{\'a}nchez and Quir{\'o}s, {Jos{\'e} Ram{\'o}n} and Mar{\'i}a-Dolores Chirlaque and Antonio Agudo and Mikael Johansson and Kjell Grankvist and Marie-Christine Boutron-Ruault and Fran{\c c}oise Clavel-Chapelon and Guy Fagherazzi and Elisabete Weiderpass and Elio Riboli and Brennan, {Paul J} and Paolo Vineis and Mattias Johansson",

note = "{\textcopyright}2013 AACR.",

year = "2014",

month = mar,

doi = "10.1158/1055-9965.EPI-13-0770",

language = "English",

volume = "23",

pages = "461--8",

journal = "Cancer Epidemiology, Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "3",

}

Chuang, S-C, Fanidi, A, Ueland, PM, Relton, C, Midttun, O, Vollset, SE, Gunter, MJ, Seckl, 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, Sánchez, M-J, Quirós, 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 2014, 'Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk', Cancer Epidemiology, Biomarkers and Prevention, vol. 23, no. 3, pp. 461-8. https://doi.org/10.1158/1055-9965.EPI-13-0770

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 - Seckl, 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 - Sánchez, María-José

AU - Quirós, José Ramón

AU - Chirlaque, María-Dolores

AU - Agudo, Antonio

AU - Johansson, Mikael

AU - Grankvist, Kjell

AU - Boutron-Ruault, Marie-Christine

AU - Clavel-Chapelon, Françoise

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 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.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 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.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 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.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 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.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.

KW - Adult

KW - Aged

KW - Case-Control Studies

KW - Cohort Studies

KW - Europe

KW - Female

KW - Humans

KW - Kynurenine

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Questionnaires

KW - Risk Factors

KW - Tryptophan

KW - Tumor Markers, Biological

U2 - 10.1158/1055-9965.EPI-13-0770

DO - 10.1158/1055-9965.EPI-13-0770

M3 - Article (Academic Journal)

C2 - 24357106

SN - 1055-9965

VL - 23

SP - 461

EP - 468

JO - Cancer Epidemiology, Biomarkers and Prevention

JF - Cancer Epidemiology, Biomarkers and Prevention

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Handle.net

Fingerprint

Projects

MRC UoB UNITE Unit - Programme 2

Cite this