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

doi:10.1136/bmj.k4981

. 2019 Jan 3:364:k4981.

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^{1

2}, Tricia L Larose^{3

4}, Allison Hodge^{5

6}, Florence Guida³, Arnulf Langhammer⁷, Kjell Grankvist⁸, Klaus Meyer⁹, Qiuyin Cai¹⁰, Alan A Arslan^{11

12}, Anne Zeleniuch-Jacquotte¹², Demetrius Albanes¹³, Graham G Giles^{5

6}, Howard D Sesso^{14

15

16}, I-Min Lee^{14

16}, J Michael Gaziano^{15

16

17}, Jian-Min Yuan^{18

19}, Judith Hoffman Bolton²⁰, Julie E Buring^{14

16}, Kala Visvanathan²⁰, Loic Le Marchand²¹, Mark P Purdue²², Neil E Caporaso²², Øivind Midttun⁹, Per M Ueland^{23

24}, Ross L Prentice²⁵, Stephanie J Weinstein¹³, Victoria L Stevens²⁶, Wei Zheng¹⁰, William J Blot¹⁰, Xiao-Ou Shu¹⁰, Xuehong Zhang²⁷, Yong-Bing Xiang²⁸, Woon-Puay Koh²⁹, Kristian Hveem^{4

7}, Cynthia A Thomson³⁰, Mary Pettinger²⁵, Gunnar Engström³¹, Hans Brunnström³², Roger L Milne^{5

6}, Meir J Stampfer^{14

27

33}, Jiali Han^{34

35}, Mikael Johansson³⁶, Paul Brennan³, Gianluca Severi^{5

37

38}, Mattias Johansson³

Affiliations

¹ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France david.muller@imperial.ac.uk.
² Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London W2 1PG, UK.
³ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
⁴ KG Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁵ Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
⁷ HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
⁸ Department of Medical Biosciences, Umeå University, Umeå, Sweden.
⁹ Bevital AS, Bergen, Norway.
¹⁰ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer, Vanderbilt University School of Medicine, Nashville, TN, USA.
¹¹ Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
¹² Department of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA.
¹³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁴ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
¹⁵ Division of Aging, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁶ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁷ Boston VA Medical Center, Boston, MA, USA.
¹⁸ UPMC Hillman Cancer Center, University of Pittsburgh, USA.
¹⁹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, USA.
²⁰ George 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.
²¹ Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA.
²² Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
²³ Department of Clinical Science, University of Bergen, Bergen, Norway.
²⁴ Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
²⁵ Division of Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
²⁶ Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
²⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁸ State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
²⁹ Duke-NUS Medical School Singapore, Singapore.
³⁰ Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
³¹ Department of Clinical Science in Malmö, Lund University, Malmö, Sweden.
³² Pathology, Department of Clinical Sciences Lund, Laboratory Medicine Region Skåne, Lund University, Lund, Sweden.
³³ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
³⁴ Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
³⁵ Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
³⁶ Department of Radiation Sciences, Umeå University, Umeå, Sweden.
³⁷ Italian Institute for Genomic Medicine (IIGM), Torino, Italy.
³⁸ Centre de Recherche en Epidemiologie et Santé des Populations (CESP) UMR1018 Inserm, Facultés de Médicine Université Paris-Saclay, UPS, UVSQ, Villejuif, France.

PMID: 30606716
PMCID: PMC6315896
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 et al. BMJ. 2019.

. 2019 Jan 3:364:k4981.

doi: 10.1136/bmj.k4981.

Authors

Affiliations

¹ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France david.muller@imperial.ac.uk.
² Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London W2 1PG, UK.
³ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
⁴ KG Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁵ Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
⁷ HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
⁸ Department of Medical Biosciences, Umeå University, Umeå, Sweden.
⁹ Bevital AS, Bergen, Norway.
¹⁰ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer, Vanderbilt University School of Medicine, Nashville, TN, USA.
¹¹ Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
¹² Department of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA.
¹³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁴ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
¹⁵ Division of Aging, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁶ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁷ Boston VA Medical Center, Boston, MA, USA.
¹⁸ UPMC Hillman Cancer Center, University of Pittsburgh, USA.
¹⁹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, USA.
²⁰ George 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.
²¹ Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA.
²² Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
²³ Department of Clinical Science, University of Bergen, Bergen, Norway.
²⁴ Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
²⁵ Division of Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
²⁶ Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
²⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁸ State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
²⁹ Duke-NUS Medical School Singapore, Singapore.
³⁰ Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
³¹ Department of Clinical Science in Malmö, Lund University, Malmö, Sweden.
³² Pathology, Department of Clinical Sciences Lund, Laboratory Medicine Region Skåne, Lund University, Lund, Sweden.
³³ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
³⁴ Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
³⁵ Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
³⁶ Department of Radiation Sciences, Umeå University, Umeå, Sweden.
³⁷ Italian Institute for Genomic Medicine (IIGM), Torino, Italy.
³⁸ Centre de Recherche en Epidemiologie et Santé des Populations (CESP) UMR1018 Inserm, Facultés de Médicine Université Paris-Saclay, UPS, UVSQ, Villejuif, France.

PMID: 30606716
PMCID: PMC6315896
DOI: 10.1136/bmj.k4981

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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Conflict of interest statement

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.

Figures

**Fig 1**
Odds ratios for doubling in high sensitivity C reactive protein (hsCRP) concentration, overall and by participant characteristics. P values are from likelihood ratio tests of the interaction between hsCRP and each covariate

**Fig 2**
Odds ratios for doubling in high sensitivity C reactive protein (hsCRP) concentration for current smokers by participant characteristics. P values are from likelihood ratio tests of the interaction between hsCRP and each covariate

**Fig 3**
Odds ratios for doubling in high sensitivity C reactive protein (hsCRP) concentration for former smokers by participant characteristics. P values are from likelihood ratio tests of the interaction between hsCRP and each covariate

**Fig 4**
Current smokers A overall (n=2199 case-control pairs) and B with time from blood draw to diagnosis ≤2 years (n=224 case-control pairs)

See this image and copyright information in PMC

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References

1. Stewart BW, Wild CP, eds. World Cancer Report 2014. International Agency for Research on Cacner, 2014.
1. World Health Organization. Cancer Fact Sheet. http://www.who.int/mediacentre/factsheets/fs297/en/.
1. Munn LL. Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med 2017;9:e1370. 10.1002/wsbm.1370 - DOI - PMC - PubMed
1. Kushner I, Rzewnicki D, Samols D. What does minor elevation of C-reactive protein signify? Am J Med 2006;119:166.e17-28. - PubMed
1. Leuzzi G, Galeone C, Gisabella M, et al. Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis. Tumori 2016;102:441-9. 10.5301/tj.5000522 - DOI - PubMed

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[1] Stewart BW, Wild CP, eds. World Cancer Report 2014. International Agency for Research on Cacner, 2014.

[2] Stewart BW, Wild CP, eds. World Cancer Report 2014. International Agency for Research on Cacner, 2014.

[3] World Health Organization. Cancer Fact Sheet. http://www.who.int/mediacentre/factsheets/fs297/en/.

[4] World Health Organization. Cancer Fact Sheet. http://www.who.int/mediacentre/factsheets/fs297/en/.

[5] Munn LL. Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med 2017;9:e1370. 10.1002/wsbm.1370 - DOI - PMC - PubMed

[6] Munn LL. Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med 2017;9:e1370. 10.1002/wsbm.1370 - DOI - PMC - PubMed

[7] Kushner I, Rzewnicki D, Samols D. What does minor elevation of C-reactive protein signify? Am J Med 2006;119:166.e17-28. - PubMed

[8] Kushner I, Rzewnicki D, Samols D. What does minor elevation of C-reactive protein signify? Am J Med 2006;119:166.e17-28. - PubMed

[9] Leuzzi G, Galeone C, Gisabella M, et al. Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis. Tumori 2016;102:441-9. 10.5301/tj.5000522 - DOI - PubMed

[10] Leuzzi G, Galeone C, Gisabella M, et al. Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis. Tumori 2016;102:441-9. 10.5301/tj.5000522 - DOI - PubMed

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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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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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Abstract

Conflict of interest statement

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