title: Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.
abstract: OBJECTIVE
  Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.
  
  
  METHODS
  We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.
  
  
  RESULTS
  Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend=0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend=0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend=0.05]. In analyses restricted to serous ovarian cancer (n=83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend=0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend=0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5years before diagnosis (n=56).
  
  
  CONCLUSIONS
  These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address: britton.trabert@nih.gov.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA; HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Frederick, MD, USA.
authors.forename: Ligia
authors.initials: L
authors.lastname: Pinto
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.affiliation: HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Frederick, MD, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Kemp
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology*; D002097:C-Reactive Protein / Q000276:immunology*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D053582:Interleukin-1alpha / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D016015:Logistic Models; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000276:immunology*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology*; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Circulating inflammation markers; Cytokines; Inflammation; Nested case–control study; Ovarian cancer; Pre-diagnostic