title: Circulating inflammation markers and prospective risk for lung cancer.
abstract: BACKGROUND
  Despite growing recognition of an etiologic role for inflammation in lung carcinogenesis, few prospective epidemiologic studies have comprehensively investigated the association of circulating inflammation markers with lung cancer.
  
  
  METHODS
  We conducted a nested case-control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively.
  
  
  RESULTS
  Of 68 evaluable markers, 11 were statistically significantly associated with lung cancer risk (P trend across marker categories < .05), including acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA]), proinflammatory cytokines (soluble tumor necrosis factor receptor 2 [sTNFRII]), anti-inflammatory cytokines (interleukin 1 receptor antagonist [IL-1RA]), lymphoid differentiation cytokines (interleukin 7 [IL-7]), growth factors (transforming growth factor alpha [TGF-A]), and chemokines (epithelial neutrophil-activating peptide 78 [ENA 78/CXCL5], monokine induced by gamma interferon [MIG/CXCL9], B cell-attracting chemokine 1 [BCA-1/CXCL13], thymus activation regulated chemokine [TARC/CCL17], macrophage-derived chemokine [MDC/CCL22]). Elevated marker levels were associated with increased lung cancer risk, with odds ratios comparing the highest vs the lowest group ranging from 1.47 (IL-7) to 2.27 (CRP). For IL-1RA, elevated levels were associated with decreased lung cancer risk (OR = 0.71; 95% confidence interval = 0.51 to 1.00). Associations did not differ by smoking, lung cancer histology, or latency. A cross-validated inflammation score using four independent markers (CRP, BCA-1/CXCL13, MDC/CCL22, and IL-1RA) provided good separation in 10-year lung cancer cumulative risks among former smokers (quartile [Q] 1 = 1.1% vs Q4 = 3.1%) and current smokers (Q1 = 2.3% vs Q4 = 7.9%) even after adjustment for smoking.
  
  
  CONCLUSIONS
  Some circulating inflammation marker levels are associated with prospective lung cancer risk.
authors.affiliation: Affiliations of authors: Infections and Immunoepidemiology Branch (MSS, AH, EAE, JK, AKC), Biostatistics Branch (RMP, HAK), and Genetic Epidemiology Branch (NEC), Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; HPV Immunology Laboratory, SAIC-Frederick Inc., Frederick, MD (TJK, GS, LAP); Department of Statistics, Dongguk University, Seoul, Korea (J-HP).
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Kemp
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.forename: Gloriana
authors.initials: G
authors.lastname: Shelton
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D018925:Chemokines; D016207:Cytokines; D000685:Serum Amyloid A Protein; D016211:Transforming Growth Factor alpha; D002097:C-Reactive Protein