Interferon-γ-induced inflammatory markers and the risk of cancer: the Hordaland Health Study

Cancer. 2014 Nov 1;120(21):3370-7. doi: 10.1002/cncr.28869. Epub 2014 Jun 19.


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.

Keywords: CRP; cancer; cohort study; immune activation; inflammation; kynurenine-to-tryptophan ratio; neopterin; risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • C-Reactive Protein / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / blood*
  • Inflammation / pathology
  • Interferon-gamma / blood
  • Interferon-gamma / metabolism*
  • Kaplan-Meier Estimate
  • Kynurenine / blood*
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / pathology
  • Neopterin / blood*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Tryptophan / blood


  • Biomarkers, Tumor
  • Kynurenine
  • Neopterin
  • Interferon-gamma
  • Tryptophan
  • C-Reactive Protein