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Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
Author(s) -
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 XiaoOu,
Zheng Wei,
Arslan Alan A.,
ZeleniuchJacquotte 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 YongBing,
Li HongLan,
Gao YuTang,
Visvanathan Kala,
Ueland Per M.,
Midttun Øivind,
Ulvi Arve,
Buring Julie E.,
Lee IMin,
Sesso Howard D.,
Gaziano J. Michael,
Manjer Jonas,
Relton Caroline,
Koh WoonPuay,
Brennan Paul,
Johansson Mattias,
Yuan JianMin
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32555
Subject(s) - lung cancer , medicine , neopterin , oncology , kynurenine , prospective cohort study , cancer , odds ratio , cohort , cohort study , gastroenterology , immunology , biology , tryptophan , biochemistry , amino acid
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 p trend < 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.