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

Authors

  • Hui Zuo MD, PhD,

    Corresponding author
    1. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
    2. Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway
    • Corresponding author: Hui Zuo, MD, PhD, Department of Global Public Health and Primary Care, University of Bergen, Kalfarveien 31, N-5020 Bergen, Norway. Fax: (011) 47-55586130. hui.zuo@igs.uib.no

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  • Grethe S. Tell PhD, MPH,

    1. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
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  • Stein E. Vollset MD, DrPH,

    1. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
    2. Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway
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  • Per M. Ueland MD, PhD,

    1. Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway
    2. Laboratory for Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway
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  • Ottar Nygård MD, PhD,

    1. Section for Cardiology, Department of Clinical Science, University of Bergen, Norway
    2. Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
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  • Øivind Midttun PhD,

    1. Bevital A/S, Bergen, Norway
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  • Klaus Meyer PhD,

    1. Bevital A/S, Bergen, Norway
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  • Arve Ulvik PhD,

    1. Bevital A/S, Bergen, Norway
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  • Simone J.P.M. Eussen PhD

    1. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
    2. Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway
    3. Department of Epidemiology, School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, the Netherlands
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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. Cancer 2014;120:3370–3377. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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