title: Interferon-γ-induced inflammatory markers and the risk of cancer: the Hordaland Health Study.
abstract: BACKGROUND
  It has been reported that interferon-γ (IFN-γ)-induced inflammatory markers, such as circulating neopterin and kynurenine-to-tryptophan ratio (KTR), are increased in patients with cancer and are also a predictor of poor prognosis. However, whether baseline levels of these makers are associated with subsequent cancer risk in the general population remains unknown.
  
  
  METHODS
  We conducted a prospective analysis of the Hordaland Health Study in 6594 adults without known cancer at baseline who were enrolled between April 1998 and June 1999. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariate Cox proportional hazards regression models adjusted for sex, age, body mass index, smoking status, and renal function.
  
  
  RESULTS
  A total of 971 incident cancer cases (507 men and 464 women) were identified over a median follow-up time of 12 years. Baseline plasma neopterin, KTR and C-reactive protein (CRP) were significantly associated with an increased risk of overall cancer in models adjusted for covariates (P for trend across quartiles = .006 for neopterin, .022 for KTR, and .005 for CRP). The multivariate-adjusted HR (95% CI) per SD increment in similar models were 1.09 (1.03-1.16) for neopterin, 1.07 (1.01-1.14) for KTR, and 1.04 (0.98-1.10) for CRP. The associations between the inflammatory markers and risk of major specific cancer types were also provided.
  
  
  CONCLUSIONS
  Our findings indicate that plasma neopterin, KTR, and CRP are associated with a significantly increased risk of overall cancer. Our study revealed novel evidence regarding the role of IFN-γ-induced inflammation in human carcinogenesis.
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Hui
authors.initials: H
authors.lastname: Zuo
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D019798:Neopterin / Q000097:blood*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014364:Tryptophan / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D002097:C-Reactive Protein
keywords: CRP; cancer; cohort study; immune activation; inflammation; kynurenine-to-tryptophan ratio; neopterin; risk