Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Joyce Y. Huang, Tricia L. Larose, Hung N. Luu, Renwei Wang, Anouar Fanidi, Karine Alcala, Victoria L. Stevens, Stephanie J. Weinstein, Demetrius Albanes, Neil E. Caporaso, Mark P. Purdue, Regina G. Ziegler, Neal D. Freedman, Qing Lan, Ross L. Prentice, Mary Pettinger, Cynthia A. Thomson, Qiuyin Cai, Jie Wu, William J. BlotXiao Ou Shu, Wei Zheng, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Loïc Le Marchand, Lynn R. Wilkens, Christopher A. Haiman, Xuehong Zhang, Meir J. Stampfer, Jiali Han, Graham G. Giles, Allison M. Hodge, Gianluca Severi, Mikael Johansson, Kjell Grankvist, Arnulf Langhammer, Kristian Hveem, Yong Bing Xiang, Hong Lan Li, Yu Tang Gao, Kala Visvanathan, Per M. Ueland, Øivind Midttun, Arve Ulvi, Julie E. Buring, I. Min Lee, Howard D. Sesso, J. Michael Gaziano, Jonas Manjer, Caroline Relton, Woon Puay Koh, Paul Brennan, Mattias Johansson, Jian Min Yuan

Research output: Contribution to journalArticle

Abstract

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case–control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15–1.75), 1.42 (1.14–1.76) and 1.45 (1.13–1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan–kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

Kynurenine
Lung Neoplasms
Biomarkers
Tryptophan
Quinolinic Acid
Neopterin
Lung
Carcinogenesis
Odds Ratio
Confidence Intervals
Cotinine
Squamous Cell Carcinoma
Mass Spectrometry
Logistic Models
Smoking
Inflammation
Serum
Research

Keywords

  • kynurenine
  • lung cancer
  • neopterin
  • quinolinic acid
  • tryptophan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3). / Huang, Joyce Y.; Larose, Tricia L.; Luu, Hung N.; Wang, Renwei; Fanidi, Anouar; Alcala, Karine; Stevens, Victoria L.; Weinstein, Stephanie J.; Albanes, Demetrius; Caporaso, Neil E.; Purdue, Mark P.; Ziegler, Regina G.; Freedman, Neal D.; Lan, Qing; Prentice, Ross L.; Pettinger, Mary; Thomson, Cynthia A.; Cai, Qiuyin; Wu, Jie; Blot, William J.; Shu, Xiao Ou; Zheng, Wei; Arslan, Alan A.; Zeleniuch-Jacquotte, Anne; Le Marchand, Loïc; Wilkens, Lynn R.; Haiman, Christopher A.; Zhang, Xuehong; Stampfer, Meir J.; Han, Jiali; Giles, Graham G.; Hodge, Allison M.; Severi, Gianluca; Johansson, Mikael; Grankvist, Kjell; Langhammer, Arnulf; Hveem, Kristian; Xiang, Yong Bing; Li, Hong Lan; Gao, Yu Tang; Visvanathan, Kala; Ueland, Per M.; Midttun, Øivind; Ulvi, Arve; Buring, Julie E.; Lee, I. Min; Sesso, Howard D.; Gaziano, J. Michael; Manjer, Jonas; Relton, Caroline; Koh, Woon Puay; Brennan, Paul; Johansson, Mattias; Yuan, Jian Min.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Huang, JY, Larose, TL, Luu, HN, Wang, R, Fanidi, A, Alcala, K, Stevens, VL, Weinstein, SJ, Albanes, D, Caporaso, NE, Purdue, MP, Ziegler, RG, Freedman, ND, Lan, Q, Prentice, RL, Pettinger, M, Thomson, CA, Cai, Q, Wu, J, Blot, WJ, Shu, XO, Zheng, W, Arslan, AA, Zeleniuch-Jacquotte, A, Le Marchand, L, Wilkens, LR, Haiman, CA, Zhang, X, Stampfer, MJ, Han, J, Giles, GG, Hodge, AM, Severi, G, Johansson, M, Grankvist, K, Langhammer, A, Hveem, K, Xiang, YB, Li, HL, Gao, YT, Visvanathan, K, Ueland, PM, Midttun, Ø, Ulvi, A, Buring, JE, Lee, IM, Sesso, HD, Gaziano, JM, Manjer, J, Relton, C, Koh, WP, Brennan, P, Johansson, M & Yuan, JM 2019, 'Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)', International Journal of Cancer. https://doi.org/10.1002/ijc.32555
Huang, Joyce Y. ; Larose, Tricia L. ; Luu, Hung N. ; Wang, Renwei ; Fanidi, Anouar ; Alcala, Karine ; Stevens, Victoria L. ; Weinstein, Stephanie J. ; Albanes, Demetrius ; Caporaso, Neil E. ; Purdue, Mark P. ; Ziegler, Regina G. ; Freedman, Neal D. ; Lan, Qing ; Prentice, Ross L. ; Pettinger, Mary ; Thomson, Cynthia A. ; Cai, Qiuyin ; Wu, Jie ; Blot, William J. ; Shu, Xiao Ou ; Zheng, Wei ; Arslan, Alan A. ; Zeleniuch-Jacquotte, Anne ; Le Marchand, Loïc ; Wilkens, Lynn R. ; Haiman, Christopher A. ; Zhang, Xuehong ; Stampfer, Meir J. ; Han, Jiali ; Giles, Graham G. ; Hodge, Allison M. ; Severi, Gianluca ; Johansson, Mikael ; Grankvist, Kjell ; Langhammer, Arnulf ; Hveem, Kristian ; Xiang, Yong Bing ; Li, Hong Lan ; Gao, Yu Tang ; Visvanathan, Kala ; Ueland, Per M. ; Midttun, Øivind ; Ulvi, Arve ; Buring, Julie E. ; Lee, I. Min ; Sesso, Howard D. ; Gaziano, J. Michael ; Manjer, Jonas ; Relton, Caroline ; Koh, Woon Puay ; Brennan, Paul ; Johansson, Mattias ; Yuan, Jian Min. / Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3). In: International Journal of Cancer. 2019.
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abstract = "Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case–control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95{\%} confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20–30{\%} higher risk, and tryptophan with a 15{\%} lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95{\%} CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15–1.75), 1.42 (1.14–1.76) and 1.45 (1.13–1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan–kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.",
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TY - JOUR

T1 - Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

AU - Huang, Joyce Y.

AU - Larose, Tricia L.

AU - Luu, Hung N.

AU - Wang, Renwei

AU - Fanidi, Anouar

AU - Alcala, Karine

AU - Stevens, Victoria L.

AU - Weinstein, Stephanie J.

AU - Albanes, Demetrius

AU - Caporaso, Neil E.

AU - Purdue, Mark P.

AU - Ziegler, Regina G.

AU - Freedman, Neal D.

AU - Lan, Qing

AU - Prentice, Ross L.

AU - Pettinger, Mary

AU - Thomson, Cynthia A.

AU - Cai, Qiuyin

AU - Wu, Jie

AU - Blot, William J.

AU - Shu, Xiao Ou

AU - Zheng, Wei

AU - Arslan, Alan A.

AU - Zeleniuch-Jacquotte, Anne

AU - Le Marchand, Loïc

AU - Wilkens, Lynn R.

AU - Haiman, Christopher A.

AU - Zhang, Xuehong

AU - Stampfer, Meir J.

AU - Han, Jiali

AU - Giles, Graham G.

AU - Hodge, Allison M.

AU - Severi, Gianluca

AU - Johansson, Mikael

AU - Grankvist, Kjell

AU - Langhammer, Arnulf

AU - Hveem, Kristian

AU - Xiang, Yong Bing

AU - Li, Hong Lan

AU - Gao, Yu Tang

AU - Visvanathan, Kala

AU - Ueland, Per M.

AU - Midttun, Øivind

AU - Ulvi, Arve

AU - Buring, Julie E.

AU - Lee, I. Min

AU - Sesso, Howard D.

AU - Gaziano, J. Michael

AU - Manjer, Jonas

AU - Relton, Caroline

AU - Koh, Woon Puay

AU - Brennan, Paul

AU - Johansson, Mattias

AU - Yuan, Jian Min

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case–control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15–1.75), 1.42 (1.14–1.76) and 1.45 (1.13–1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan–kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

AB - Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case–control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15–1.75), 1.42 (1.14–1.76) and 1.45 (1.13–1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan–kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

KW - kynurenine

KW - lung cancer

KW - neopterin

KW - quinolinic acid

KW - tryptophan

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