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

Research output: Contribution to journalArticle


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.


  • 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
  • Roger L. Milne
  • Meir J. Stampfer
  • Jiali Han
  • Mikael Johansson
  • Paul Brennan
  • Gianluca Severi
  • Mattias Johansson
External organisations
  • International Agency for Research on Cancer, World Health Organization
  • Imperial College London
  • Norwegian University of Science and Technology
  • Cancer Council Victoria
  • University of Melbourne
  • Umeå University
  • Bevital AS
  • Vanderbilt University
  • New York University
  • National Cancer Institute, USA
  • Harvard University
  • Brigham and Women's Hospital / Harvard Medical School
  • Veterans Health Administration
  • University of Pittsburgh
  • Johns Hopkins Bloomberg School of Public Health
  • University of Bergen
  • Haukeland University Hospital
  • American Cancer Society
  • Renji Hospital
  • Duke–NUS Medical School
  • Italian Institute for Genomic Medicine (IIGM)
  • University of Arizona
  • Fred Hutchinson Cancer Research Center
  • Region Skåne
  • Versailles Saint-Quentin-en-Yvelines University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Article numberk4981
JournalBMJ (Online)
Publication statusPublished - 2019
Publication categoryResearch