title: Cigarette smoking and variations in systemic immune and inflammation markers.
abstract: BACKGROUND
  A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease.
  
  
  METHODS
  Levels of 78 inflammation, immune, and metabolic markers were measured using multiplex immune assays in 1819 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) participants aged 55 to 74 years from three existing nested case-control studies. These data were made representative of the entire PLCO screening arm through reweighting with weights estimated in logistic regression models. We assessed associations between smoking status, cigarettes smoked per day, and time since quitting with dichotomized marker levels using adjusted weighted logistic regression models.
  
  
  RESULTS
  Current smoking was associated with 10 inflammation markers after correcting for multiple testing, encompassing several components of the immune/inflammation response. Levels of seven of these markers (interleukin [IL]-15, IL-1RA, IL-1β, IL-16, stem cell factor, soluble interleukin 6 receptor, and soluble vascular endothelial growth factor receptor 3) were lower among current smokers (n = 414) when compared with never smokers (n = 548), with odds ratios (ORs) ranging from 0.44 to 0.27, while levels of CC motif ligand (CCL)/thymus and activation regulated chemokine (CCL17/TARC) (OR = 4.08, 95% confidence interval [CI] = 2.01 to 8.25), CCL11/EOTAXIN (OR = 2.57, 95% CI = 1.45 to 4.55), and C-reactive protein (CRP) (OR = 2.54, 95% CI = 1.29 to 4.98) were elevated. These markers were not associated with cigarettes per day among current smokers, but there were trends in IL-15, IL-1RA, IL-1β, CCL17/TARC, CCL11/EOTAXIN, and CRP levels across categories of years since quitting smoking.
  
  
  CONCLUSIONS
  Smoking is associated with a broad range of alterations in systemic immune and inflammation marker levels among older, long-term smokers. Smoking cessation may result in marker levels reverting back to those of never smokers over time.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC). shielsms@mail.nih.gov.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Cari M
authors.initials: CM
authors.lastname: Kitahara
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Michael
authors.initials: M
authors.lastname: Furr
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (MSS, HAK, NDF, MPP, NW, BT, CMK, JJG, EAE, NEC, AH, ANK); Information Management Services, Inc, Rockville, MD (MF); Joint Program for Survey Methodology, University of Maryland, College Park, MD (YL); Leidos Biomedical Research, Inc., Frederick, MD (TJK, LAP); Center for Tobacco Products, Food and Drug Administration, Rockville, MD (CMC).
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000276:immunology; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D019409:Interleukin-15 / Q000097:blood; D019410:Interleukin-16 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D016015:Logistic Models; D008175:Lung Neoplasms / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000276:immunology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000097:blood; D012907:Smoking / Q000097:blood / Q000276:immunology*; D016540:Smoking Cessation; D019089:Stem Cell Factor / Q000097:blood; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000097:blood
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D019409:Interleukin-15; D019410:Interleukin-16; D053583:Interleukin-1beta; D019947:Receptors, Interleukin-6; D019089:Stem Cell Factor; D002097:C-Reactive Protein; D040321:Vascular Endothelial Growth Factor Receptor-3