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 language | English (US) |
|---|---|
| Pages (from-to) | 2394-2405 |
| Number of pages | 12 |
| Journal | International Journal of Cancer |
| Volume | 146 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2020 |
Keywords
- kynurenine
- lung cancer
- neopterin
- quinolinic acid
- tryptophan
ASJC Scopus subject areas
- Oncology
- Cancer Research
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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). / 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, Vol. 146, No. 9, 01.05.2020, p. 2394-2405.Research output: Contribution to journal › Article › peer-review
}
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
N1 - Funding Information: We thank all participants, investigators and staff of the 20 original cohort studies that contributed data and biospecimens to the international Lung Cancer Cohort Consortium (LC3) project. For the Nurses’ Health Study and the Health Professionals Follow-up Study, we acknowledge following state cancer registries for their help to ascertain cancer cases: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. For the Campaign Against Cancer and Stroke (CLUE I) and the Campaign Against Cancer and Heart Disease (CLUE II) cohorts, we thank the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene for providing Cancer Incidence Data, The Lung Cancer Cohort Consortium (LC3) was supported by National Institutes of Health/National Cancer Institute grant No. 1U01CA155340. The work of T. L. Larose presented in this paper was undertaken during a postdoctoral placement at the International Agency for Research on Cancer, within the framework of an agreement between the Research Council of Norway and the Norwegian University of Science and Technology. We acknowledge the main funding sources to individual participating cohorts (Funding agency, grant number): The Nurses’ Health Study and the Health Professionals Follow-up Study (NIH UM1CA167552, UM1CA186107 and P01CA87969); the Shanghai Cohort Study and the Singapore Chinese Health Study (NIH R01CA1144034 and UM1CA182876); the Shanghai Men’s Health Study (NIH UM1 CA173640); The Shanghai Women’s Health Study (NIH UM1 CA182910); The Southern Community Cohort Study (NIH R01 CA092447 and U01 CA202979); The Women’s Health Initiative (NIH contracts HHSN268201100046C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C and HHSN271201600004C); the Women’s Health Study (NIH CA047988, CA182913, HL043851, HL080467 and HL099355), the Physicians’ Health Study (NIH CA097193, CA34944, CA40360, HL26490 and HL34595), and the New York University Women’s Health Study (NIH UM1 CA182934, P30 CA016087 and P30 ES000260). The Alpha-Tocopherol Beta-Carotene Study (HHSN261201500005C and NCI Intramural Research Program); the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) and contracts from the Division of Cancer Prevention, NCI); the Melbourne Collaborative Cohort Study (VicHealth and Cancer Council Victoria and Australian National Health and Medical Research Council grants 209057, 396414 and 1074383); The CLUE I and II (the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries); and the HUNT Study is a collaboration between NTNU (Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences), Trøndelag County Council, Central Norway Health Authority and the Norwegian Institute of Public Health. Funding Information: We thank all participants, investigators and staff of the 20 original cohort studies that contributed data and biospecimens to the international Lung Cancer Cohort Consortium (LC3) project. For the Nurses? Health Study and the Health Professionals Follow-up Study, we acknowledge following state cancer registries for their help to ascertain cancer cases: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. For the Campaign Against Cancer and Stroke (CLUE I) and the Campaign Against Cancer and Heart Disease (CLUE II) cohorts, we thank the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene for providing Cancer Incidence Data, The Lung Cancer Cohort Consortium (LC3) was supported by National Institutes of Health/National Cancer Institute grant No. 1U01CA155340. The work of T. L. Larose presented in this paper was undertaken during a postdoctoral placement at the International Agency for Research on Cancer, within the framework of an agreement between the Research Council of Norway and the Norwegian University of Science and Technology. We acknowledge the main funding sources to individual participating cohorts (Funding agency, grant number): The Nurses? Health Study and the Health Professionals Follow-up Study (NIH UM1CA167552, UM1CA186107 and P01CA87969); the Shanghai Cohort Study and the Singapore Chinese Health Study (NIH R01CA1144034 and UM1CA182876); the Shanghai Men's Health Study (NIH UM1 CA173640); The Shanghai Women's Health Study (NIH UM1 CA182910); The Southern Community Cohort Study (NIH R01 CA092447 and U01 CA202979); The Women's Health Initiative (NIH contracts HHSN268201100046C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C and HHSN271201600004C); the Women's Health Study (NIH CA047988, CA182913, HL043851, HL080467 and HL099355), the Physicians? Health Study (NIH CA097193, CA34944, CA40360, HL26490 and HL34595), and the New York University Women's Health Study (NIH UM1 CA182934, P30 CA016087 and P30 ES000260). The Alpha-Tocopherol Beta-Carotene Study (HHSN261201500005C and NCI Intramural Research Program); the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) and contracts from the Division of Cancer Prevention, NCI); the Melbourne Collaborative Cohort Study (VicHealth and Cancer Council Victoria and Australian National Health and Medical Research Council grants 209057, 396414 and 1074383). Publisher Copyright: © 2019 UICC
PY - 2020/5/1
Y1 - 2020/5/1
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
UR - http://www.scopus.com/inward/record.url?scp=85069910415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069910415&partnerID=8YFLogxK
U2 - 10.1002/ijc.32555
DO - 10.1002/ijc.32555
M3 - Article
C2 - 31276202
AN - SCOPUS:85069910415
VL - 146
SP - 2394
EP - 2405
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 9
ER -