Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium

David C. Muller; Tricia L. Larose; Allison Hodge; Florence Guida; Arnulf Langhammer; Kjell Grankvist; Klaus Meyer; Qiuyin Cai; Alan A. Arslan; Anne Zeleniuch-Jacquotte; Demetrius Albanes; Graham G. Giles; Howard D. Sesso; I. Min Lee; J. Michael Gaziano; Jian Min Yuan; Judith Hoffman Bolton; Julie E. Buring; Kala Visvanathan; Loic Le Marchand; Mark P. Purdue; Neil E. Caporaso; Øivind Midttun; Per M. Ueland; Ross L. Prentice; Stephanie J. Weinstein; Victoria L. Stevens; Wei Zheng; William J. Blot; Xiao Ou Shu; Xuehong Zhang; Yong Bing Xiang; Woon Puay Koh; Kristian Hveem; Cynthia A. Thomson; Mary Pettinger; Gunnar Engström; Hans Brunnström; Roger L. Milne; Meir J. Stampfer; Jiali Han; Mikael Johansson; Paul Brennan; Gianluca Severi; Mattias Johansson

doi:10.1136/bmj.k4981

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium

David C. Muller, Tricia L. Larose, Allison Hodge, Florence Guida, Arnulf Langhammer, Kjell Grankvist, Klaus Meyer, Qiuyin Cai, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Demetrius Albanes, Graham G. Giles, Howard D. Sesso, I. Min Lee, J. Michael Gaziano, Jian Min Yuan, Judith Hoffman Bolton, Julie E. Buring, Kala Visvanathan, Loic Le MarchandMark P. Purdue, Neil E. Caporaso, Øivind Midttun, Per M. Ueland, Ross L. Prentice, Stephanie J. Weinstein, Victoria L. Stevens, Wei Zheng, William J. Blot, Xiao Ou Shu, Xuehong Zhang, Yong Bing Xiang, Woon Puay Koh, Kristian Hveem, Cynthia A. Thomson, Mary Pettinger, Gunnar Engström, Hans Brunnström, Roger L. Milne, Meir J. Stampfer, Jiali Han, Mikael Johansson, Paul Brennan, Gianluca Severi, Mattias Johansson

Health Promotion Sciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.

Original language	English (US)
Journal	BMJ (Online)
Volume	364
DOIs	https://doi.org/10.1136/bmj.k4981
State	Published - 2019

ASJC Scopus subject areas

Medicine(all)

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10.1136/bmj.k4981

Cite this

Muller, D. C., Larose, T. L., Hodge, A., Guida, F., Langhammer, A., Grankvist, K., Meyer, K., Cai, Q., Arslan, A. A., Zeleniuch-Jacquotte, A., Albanes, D., Giles, G. G., Sesso, H. D., Lee, I. M., Gaziano, J. M., Yuan, J. M., Bolton, J. H., Buring, J. E., Visvanathan, K., ... Johansson, M. (2019). Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium. BMJ (Online), 364. https://doi.org/10.1136/bmj.k4981

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : Nested case-control study within Lung Cancer Cohort Consortium. / Muller, David C.; Larose, Tricia L.; Hodge, Allison; Guida, Florence; Langhammer, Arnulf; Grankvist, Kjell; Meyer, Klaus; Cai, Qiuyin; Arslan, Alan A.; Zeleniuch-Jacquotte, Anne; Albanes, Demetrius; Giles, Graham G.; Sesso, Howard D.; Lee, I. Min; Gaziano, J. Michael; Yuan, Jian Min; Bolton, Judith Hoffman; Buring, Julie E.; Visvanathan, Kala; Le Marchand, Loic; Purdue, Mark P.; Caporaso, Neil E.; Midttun, Øivind; Ueland, Per M.; Prentice, Ross L.; Weinstein, Stephanie J.; Stevens, Victoria L.; Zheng, Wei; Blot, William J.; Shu, Xiao Ou; Zhang, Xuehong; Xiang, Yong Bing; Koh, Woon Puay; Hveem, Kristian; Thomson, Cynthia A.; Pettinger, Mary; Engström, Gunnar; Brunnström, Hans; Milne, Roger L.; Stampfer, Meir J.; Han, Jiali; Johansson, Mikael; Brennan, Paul; Severi, Gianluca; Johansson, Mattias.

In: BMJ (Online), Vol. 364, 2019.

Research output: Contribution to journal › Article › peer-review

Muller, DC, Larose, TL, Hodge, A, Guida, F, Langhammer, A, Grankvist, K, Meyer, K, Cai, Q, Arslan, AA, Zeleniuch-Jacquotte, A, Albanes, D, Giles, GG, Sesso, HD, Lee, IM, Gaziano, JM, Yuan, JM, Bolton, JH, Buring, JE, Visvanathan, K, Le Marchand, L, Purdue, MP, Caporaso, NE, Midttun, Ø, Ueland, PM, Prentice, RL, Weinstein, SJ, Stevens, VL, Zheng, W, Blot, WJ, Shu, XO, Zhang, X, Xiang, YB, Koh, WP, Hveem, K, Thomson, CA, Pettinger, M, Engström, G, Brunnström, H, Milne, RL, Stampfer, MJ, Han, J, Johansson, M, Brennan, P, Severi, G & Johansson, M 2019, 'Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium', BMJ (Online), vol. 364. https://doi.org/10.1136/bmj.k4981

Muller, David C. ; Larose, Tricia L. ; Hodge, Allison ; Guida, Florence ; Langhammer, Arnulf ; Grankvist, Kjell ; Meyer, Klaus ; Cai, Qiuyin ; Arslan, Alan A. ; Zeleniuch-Jacquotte, Anne ; Albanes, Demetrius ; Giles, Graham G. ; Sesso, Howard D. ; Lee, I. Min ; Gaziano, J. Michael ; Yuan, Jian Min ; Bolton, Judith Hoffman ; Buring, Julie E. ; Visvanathan, Kala ; Le Marchand, Loic ; Purdue, Mark P. ; Caporaso, Neil E. ; Midttun, Øivind ; Ueland, Per M. ; Prentice, Ross L. ; Weinstein, Stephanie J. ; Stevens, Victoria L. ; Zheng, Wei ; Blot, William J. ; Shu, Xiao Ou ; Zhang, Xuehong ; Xiang, Yong Bing ; Koh, Woon Puay ; Hveem, Kristian ; Thomson, Cynthia A. ; Pettinger, Mary ; Engström, Gunnar ; Brunnström, Hans ; Milne, Roger L. ; Stampfer, Meir J. ; Han, Jiali ; Johansson, Mikael ; Brennan, Paul ; Severi, Gianluca ; Johansson, Mattias. / Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : Nested case-control study within Lung Cancer Cohort Consortium. In: BMJ (Online). 2019 ; Vol. 364.

@article{2e94a04f9bce4f31b2a70b0e4d5f1fa8,

title = "Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium",

abstract = "Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.",

author = "Muller, {David C.} and Larose, {Tricia L.} and Allison Hodge and Florence Guida and Arnulf Langhammer and Kjell Grankvist and Klaus Meyer and Qiuyin Cai and Arslan, {Alan A.} and Anne Zeleniuch-Jacquotte and Demetrius Albanes and Giles, {Graham G.} and Sesso, {Howard D.} and Lee, {I. Min} and Gaziano, {J. Michael} and Yuan, {Jian Min} and Bolton, {Judith Hoffman} and Buring, {Julie E.} and Kala Visvanathan and {Le Marchand}, Loic and Purdue, {Mark P.} and Caporaso, {Neil E.} and {\O}ivind Midttun and Ueland, {Per M.} and Prentice, {Ross L.} and Weinstein, {Stephanie J.} and Stevens, {Victoria L.} and Wei Zheng and Blot, {William J.} and Shu, {Xiao Ou} and Xuehong Zhang and Xiang, {Yong Bing} and Koh, {Woon Puay} and Kristian Hveem and Thomson, {Cynthia A.} and Mary Pettinger and Gunnar Engstr{\"o}m and Hans Brunnstr{\"o}m and Milne, {Roger L.} and Stampfer, {Meir J.} and Jiali Han and Mikael Johansson and Paul Brennan and Gianluca Severi and Mattias Johansson",

note = "Funding Information: University School of Medicine, Nashville, TN, USA 10Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA 11Department of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA 12Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 13Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA 14Division of Aging, Department of Medicine, Brigham and Women{\textquoteright}s Hospital, Boston, MA, USA 15Division of Preventive Medicine, Department of Medicine, Brigham and Women{\textquoteright}s Hospital, Boston, MA, USA 16Boston VA Medical Center, Boston, MA, USA 17UPMC Hillman Cancer Center, University of Pittsburgh, USA 18Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, USA 19George W Comstock Center for Public Health Research and Prevention Health Monitoring Unit, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA 20Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA 21Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA 22Department of Clinical Science, University of Bergen, Bergen, Norway 23Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway 24Division of Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, WA, USA 25Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA 26Channing Division of Network Medicine, Department of Medicine, Brigham and Women{\textquoteright}s Hospital and Harvard Medical School, Boston, MA, USA 27State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 28Duke-NUS Medical School Singapore, Singapore 29Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA 30Department of Clinical Science in Malm{\"o}, Lund University, Malm{\"o}, Sweden 31Pathology, Department of Clinical Sciences Lund, Laboratory Medicine Region Sk{\aa}ne, Lund University, Lund, Sweden 32Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA 33Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA 34Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA 35Department of Radiation Sciences, Ume{\aa} University, Ume{\aa}, Sweden 36Italian Institute for Genomic Medicine (IIGM), Torino, Italy 37Centre de Recherche en Epidemiologie et Sant{\'e} des Populations (CESP) UMR1018 Inserm, Facult{\'e}s de M{\'e}dicine Universit{\'e} Paris-Saclay, UPS, UVSQ, Villejuif, France We thank all cohorts and all cohort participants for making this research possible. The Women{\textquoteright}s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The WHI authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full list of WHI investigators can be found in the supplementary materials. The Health Professionals Follow-up Study and NHS authors would like to thank the participants. Staff of the Health Professionals Follow-up Study and Nurses{\textquoteright} Health Study thank the cohort participants and staff for their valuable contributions as well as the following state cancer registries for their help: 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 Multiethnic Cohort Study cohort acknowledges partial funding from National Institutes of Health grant U01 CA164973. Cancer incidence data for the CLUE cohort were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W Preston Street, Room 400, Baltimore, MD 21201. The CLUE investigators acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data. Funding Information: The Lung Cancer Cohort Consortium was supported by Grant National Institutes of Health/National Cancer Institute (no 1U01CA155340-01) and The National Health and Medical Research Council (Grant ID: 1050198). DCM receives funding from a Cancer Research UK Population Research Fellowship. This work was supported by The Research Council of Norway (grant no 267776/H10). The work undertaken by TLL for this paper was conducted 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. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript. Funding Information: Contributors: DCM and TLL contributed jointly to the study. MaJand PB organised the Lung Cancer Cohort Consortium study. DCM, TLL, and FG conducted the data analysis. Data was interpreted by all authors. TLL, DCM and MaJ wrote the first draft of the manuscript. All authors read and approved the final manuscript. DCM and MaJ had full access to the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. DCM and MaJ are guarantors of the article. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: The Lung Cancer Cohort Consortium was supported by Grant National Institutes of Health/National Cancer Institute (no 1U01CA155340-01) and The National Health and Medical Research Council (Grant ID: 1050198). DCM receives funding from a Cancer Research UK Population Research Fellowship. This work was supported by The Research Council of Norway (grant no 267776/ H10). The work undertaken by TLL for this paper was conducted 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. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Publisher Copyright: {\textcopyright} 2019 BMJ Publishing Group. All rights reserved.",

year = "2019",

doi = "10.1136/bmj.k4981",

language = "English (US)",

volume = "364",

journal = "The BMJ",

issn = "0959-8146",

publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Circulating high sensitivity C reactive protein concentrations and risk of lung cancer

T2 - Nested case-control study within Lung Cancer Cohort Consortium

AU - Muller, David C.

AU - Larose, Tricia L.

AU - Hodge, Allison

AU - Guida, Florence

AU - Langhammer, Arnulf

AU - Grankvist, Kjell

AU - Meyer, Klaus

AU - Cai, Qiuyin

AU - Arslan, Alan A.

AU - Zeleniuch-Jacquotte, Anne

AU - Albanes, Demetrius

AU - Giles, Graham G.

AU - Sesso, Howard D.

AU - Lee, I. Min

AU - Gaziano, J. Michael

AU - Yuan, Jian Min

AU - Bolton, Judith Hoffman

AU - Buring, Julie E.

AU - Visvanathan, Kala

AU - Le Marchand, Loic

AU - Purdue, Mark P.

AU - Caporaso, Neil E.

AU - Midttun, Øivind

AU - Ueland, Per M.

AU - Prentice, Ross L.

AU - Weinstein, Stephanie J.

AU - Stevens, Victoria L.

AU - Zheng, Wei

AU - Blot, William J.

AU - Shu, Xiao Ou

AU - Zhang, Xuehong

AU - Xiang, Yong Bing

AU - Koh, Woon Puay

AU - Hveem, Kristian

AU - Thomson, Cynthia A.

AU - Pettinger, Mary

AU - Engström, Gunnar

AU - Brunnström, Hans

AU - Milne, Roger L.

AU - Stampfer, Meir J.

AU - Han, Jiali

AU - Johansson, Mikael

AU - Brennan, Paul

AU - Severi, Gianluca

AU - Johansson, Mattias

N1 - Funding Information: University School of Medicine, Nashville, TN, USA 10Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA 11Department of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA 12Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 13Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA 14Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA 15Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA 16Boston VA Medical Center, Boston, MA, USA 17UPMC Hillman Cancer Center, University of Pittsburgh, USA 18Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, USA 19George W Comstock Center for Public Health Research and Prevention Health Monitoring Unit, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA 20Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA 21Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA 22Department of Clinical Science, University of Bergen, Bergen, Norway 23Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway 24Division of Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, WA, USA 25Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA 26Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 27State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 28Duke-NUS Medical School Singapore, Singapore 29Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA 30Department of Clinical Science in Malmö, Lund University, Malmö, Sweden 31Pathology, Department of Clinical Sciences Lund, Laboratory Medicine Region Skåne, Lund University, Lund, Sweden 32Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA 33Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA 34Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA 35Department of Radiation Sciences, Umeå University, Umeå, Sweden 36Italian Institute for Genomic Medicine (IIGM), Torino, Italy 37Centre de Recherche en Epidemiologie et Santé des Populations (CESP) UMR1018 Inserm, Facultés de Médicine Université Paris-Saclay, UPS, UVSQ, Villejuif, France We thank all cohorts and all cohort participants for making this research possible. The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The WHI authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full list of WHI investigators can be found in the supplementary materials. The Health Professionals Follow-up Study and NHS authors would like to thank the participants. Staff of the Health Professionals Follow-up Study and Nurses’ Health Study thank the cohort participants and staff for their valuable contributions as well as the following state cancer registries for their help: 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 Multiethnic Cohort Study cohort acknowledges partial funding from National Institutes of Health grant U01 CA164973. Cancer incidence data for the CLUE cohort were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W Preston Street, Room 400, Baltimore, MD 21201. The CLUE investigators acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data. Funding Information: The Lung Cancer Cohort Consortium was supported by Grant National Institutes of Health/National Cancer Institute (no 1U01CA155340-01) and The National Health and Medical Research Council (Grant ID: 1050198). DCM receives funding from a Cancer Research UK Population Research Fellowship. This work was supported by The Research Council of Norway (grant no 267776/H10). The work undertaken by TLL for this paper was conducted 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. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript. Funding Information: Contributors: DCM and TLL contributed jointly to the study. MaJand PB organised the Lung Cancer Cohort Consortium study. DCM, TLL, and FG conducted the data analysis. Data was interpreted by all authors. TLL, DCM and MaJ wrote the first draft of the manuscript. All authors read and approved the final manuscript. DCM and MaJ had full access to the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. DCM and MaJ are guarantors of the article. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: The Lung Cancer Cohort Consortium was supported by Grant National Institutes of Health/National Cancer Institute (no 1U01CA155340-01) and The National Health and Medical Research Council (Grant ID: 1050198). DCM receives funding from a Cancer Research UK Population Research Fellowship. This work was supported by The Research Council of Norway (grant no 267776/ H10). The work undertaken by TLL for this paper was conducted 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. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Publisher Copyright: © 2019 BMJ Publishing Group. All rights reserved.

PY - 2019

Y1 - 2019

N2 - Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.

AB - Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.

UR - http://www.scopus.com/inward/record.url?scp=85059500268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059500268&partnerID=8YFLogxK

U2 - 10.1136/bmj.k4981

DO - 10.1136/bmj.k4981

M3 - Article

C2 - 30606716

AN - SCOPUS:85059500268

VL - 364

JO - The BMJ

JF - The BMJ

SN - 0959-8146

ER -

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: Nested case-control study within Lung Cancer Cohort Consortium

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