title: Association between levels of C-reactive protein and leukocytes and cancer: three repeated measurements in the Swedish AMORIS study.
abstract: OBJECTIVE
  To study levels of C-reactive protein (CRP) and leukocytes, as inflammatory markers, in the context of cancer risk.
  
  
  METHODS
  From the Apolipoprotein MOrtality RISk (AMORIS) study, we selected 102,749 persons with one measurement and 9,273 persons with three repeated measurements of CRP and leukocytes. Multivariate Cox proportional hazards regression was applied to categories of CRP (<10, 10-15, 15-25, 25-50, >50 g/L) and quartiles of leukocytes. An inflammation-based predictive score (IPS) indicated whether someone had CRP levels of more than 10 mg/L combined with leukocytes of more than 10×10(9)/L. Reverse causality was assessed by excluding those with less than 3, 5, or 7 years of follow-up. To analyze repeated measurements of CRP and leukocytes, the repeated IPS (IPSr) was calculated by adding the IPS of each measurement.
  
  
  RESULTS
  In the cohort with one measurement, there was a positive trend between CRP and risk of developing cancer, with the lowest category being the 0.99 (0.92-1.06), 1.28 (1.11-1.47), 1.27 (1.09-1.49), and 1.22 (1.01-1.48) for the second to fifth categories, respectively. This association disappeared when excluding those with follow-up of less than 3, 5, or 7 years. The association between leukocytes and cancer was slightly stronger. In the cohort with repeated measurements, the IPSr was strongly associated with cancer risk: 1.87 (1.33-2.63), 1.51 (0.56-4.06), and 4.46 (1.43-13.87) for IPSr=1, 2, and 3 compared with IPSr=0. The association remained after excluding those with follow-up of less than 1 year.
  
  
  CONCLUSIONS
  Our large, prospective cohort study adds evidence for a link between inflammatory markers and cancer risk by using repeated measurements and ascertaining reverse causality.
authors.affiliation: Cancer Epidemiology Group, Division of Cancer Studies, School of Medicine, King's College London, 3rd Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom. mieke.vanhemelrijck@kcl.ac.uk
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Hemelrijck
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: Hans
authors.initials: H
authors.lastname: Garmo
authors.forename: Niklas
authors.initials: N
authors.lastname: Hammar
authors.forename: Göran
authors.initials: G
authors.lastname: Walldius
authors.forename: Elisa
authors.initials: E
authors.lastname: Binda
authors.forename: Mats
authors.initials: M
authors.lastname: Lambe
authors.forename: Ingmar
authors.initials: I
authors.lastname: Jungner
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden
chemical_list: D014408:Biomarkers, Tumor; D002097:C-Reactive Protein