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

Krasimira Aleksandrova, Shu Chun Chuang, Heiner Boeing, Hui Zuo, Grethe S. Tell, Tobias Pischon, Mazda Jenab, Bas Bueno-De-Mesquita, Stein Emil Vollset, Øivind Midttun, Per Magne Ueland, Veronika Fedirko, Mattias Johansson, Elisabete Weiderpass, Gianluca Severi, Antoine Racine, Marie Christine Boutron-Ruault, Rudolf Kaaks, Tilman Kühn, Anne TjønnelandKim Overvad, J. Ramón Quirós, Paula Jakszyn, María José Sánchez, Miren Dorronsoro, Maria Dolores Chirlaque, Eva Ardanaz, Kay Tee Khaw, Nicholas J. Wareham, Ruth C. Travis, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Sabina Sieri, Rosario Tumino, Salvatore Panico, Anne M. May, Richard Palmqvist, Ingrid Ljuslinder, So Yeon J Kong, Heinz Freisling, Marc J. Gunter, Yunxia Lu, Amanda J. Cross, Elio Riboli, Paolo Vineis

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of the National Cancer Institute
Volume107
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aleksandrova, K., Chuang, S. C., Boeing, H., Zuo, H., Tell, G. S., Pischon, T., Jenab, M., Bueno-De-Mesquita, B., Vollset, S. E., Midttun, Ø., Ueland, P. M., Fedirko, V., Johansson, M., Weiderpass, E., Severi, G., Racine, A., Boutron-Ruault, M. C., Kaaks, R., Kühn, T., ... Vineis, P. (2015). A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk. Journal of the National Cancer Institute, 107(4). https://doi.org/10.1093/jnci/djv010