title: Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer.
abstract: BACKGROUND
  Previous studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking.
  
  
  METHODS
  Associations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case-control study. Results were validated in 532 case patients and 595 control subjects in a nested case-control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model.
  
  
  RESULTS
  Serum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%).
  
  
  CONCLUSIONS
  Although increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8 levels are associated with lung cancer risk several years before diagnosis. Combination of IL-8 and CRP are more robust biomarkers than either marker alone in predicting subsequent lung cancer.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4258, USA.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Pine
authors.forename: Leah E
authors.initials: LE
authors.lastname: Mechanic
authors.forename: Lindsey
authors.initials: L
authors.lastname: Enewold
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Zheng
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D054547:National Cancer Institute (U.S.); D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; D016209:Interleukin-8; D002097:C-Reactive Protein