A Prospective Study of the Immune System Activation Biomarker Neopterin and Colorectal Cancer Risk
Year: 2015
Type: article
Study design: Observational Study
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.
DOI: 10.1093/jnci/djv010
Authors: 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 Tjønneland, Kim 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
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Science Foundation, World Health Organization, UC Irvine Materials Research Institute, Cancer Research UK, National Institute for Health and Care Research, National Institutes of Health, University of California, Irvine, Medical Research Council, National Cancer Institute, Division of Materials Research, Division of Chemistry
OpenAlex ID: W2160179007