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A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk

Official URL:https://doi.org/10.1093/jnci/djv010
PubMed:View item in PubMed
Creators Name:Aleksandrova, K. and Chuang, S.C. and Boeing, H. and Zuo, H. and Tell, G.S. and Pischon, T. and Jenab, M. and Bueno-de-Mesquita, B. and Vollset, S.E. and Midttun, O. and Ueland, P.M. and Fedirko, V. and Johansson, M. and Weiderpass, E. and Severi, G. and Racine, A. and Boutron-Ruault, M.C. and Kaaks, R. and Kuehn, T. and Tjonneland, A. and Overvad, K. and Quiros, J.R. and Jakszyn, P. and Sanchez, M.J. and Dorronsoro, M. and Chirlaque, M.D. and Ardanaz, E. and Khaw, K.T. and Wareham, N.J. and Travis, R.C. and Trichopoulou, A. and Lagiou, P. and Trichopoulos, D. and Palli, D. and Sieri, S. and Tumino, R. and Panico, S. and May, A.M. and Palmqvist, R. and Ljuslinder, I. and Kong, S.Y.J. and Freisling, H. and Gunter, M.J. and Lu, Y. and Cross, A.J. and Riboli, E. and Vineis, P.
Journal Title:Journal of the National Cancer Institute
Journal Abbreviation:J Natl Cancer Inst
Volume:107
Number:4
Page Range:djv010
Date:April 2015
Keywords:Biological Tumor Markers, Case-Control Studies, Cellular Immunity, Colonic Neoplasms, Colorectal Neoplasms, Europe, Helper-Inducer T-Lymphocytes, Liquid Chromatography, Neopterin, Odds Ratio, Prospective Studies, Rectal Neoplasms, Sensitivity and Specificity, Tandem Mass Spectrometry
Abstract:BACKGROUND: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. RESULTS: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. CONCLUSIONS: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
ISSN:0027-8874
Publisher:Oxford University Press (U.S.A.)
Item Type:Article

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