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

Abstract

BackgroundIt 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.MethodsWe 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.ResultsA 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.ConclusionsOur 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.Interferon-γ (IFN-γ)–induced inflammatory markers were associated with an increased cancer risk in a cohort of 6594 adults followed for a median of 12 years, revealing evidence for the role of IFN-γ induced inflammation in human carcinogenesis.

Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study

“…Increased serum indoleamine 2,3‐dioxygenase (IDO), a rate‐limiting enzyme for tryptophan catabolism to kynurenine, is observed in HCC‐associated diseases, such as chronic hepatitis infection and obesity . Kynurenine/tryptophan ratio has been used as an indicator of IDO activity and was associated with increased risk of lung and overall cancers . Depletion of tryptophan and accumulation of kynurenine may suppress antitumor immune responses in chronically inflamed organs leading to activation of carcinogenesis .…”

“…46 Kynurenine/tryptophan ratio has been used as an indicator of IDO activity and was associated with increased risk of lung 22 and overall cancers. 47 Depletion of tryptophan and accumulation of kynurenine may suppress antitumor immune responses in chronically inflamed organs 43 leading to activation of carcinogenesis. 48 Increased activity of this pathway can be particularly detrimental in liver microenvironment characterised by unique immunoregulatory functions and high level of expression of dioxygenases.…”

Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer

“…Accelerated breakdown of tryptophan and increased production of neopterin were found to parallel the course of different malignant diseases and predicting poor prognosis . Moreover, elevated baseline plasma neopterin levels and KTR were associated with a significantly higher risk of developing cancer in the general population …”

“…(9) Moreover, elevated baseline plasma neopterin levels and KTR were associated with a significantly higher risk of developing cancer in the general population. (10) However, the diagnostic and prognostic role of IFN-cinduced inflammatory markers focusing on PCa is still unclear. The aim of this pilot study was to determine serum levels of neopterin and tryptophan breakdown in newly diagnosed PCa patients before RP and to test their relation to BCR after RP and prognosis (CSS).…”

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

“…One previous epidemiological study observed an association between KTR and higher risk of lung cancer . A second prospective study showed associations between KTR or neopterin and risk of cancer overall, but no association was observed for risk of lung cancer specifically, possibly due to lack of statistical power . In addition, the downstream metabolites of the kynurenine pathway such as quinolinic acid (QA) have immuno‐regulatory effects and may contribute to the development and progression of lung cancer, but has not been investigated in large epidemiological studies.…”