@article{3165544, title = "A Prospective Study of the Immune System Activation Biomarker Neopterin and Colorectal Cancer Risk", author = "Aleksandrova, Krasimira and Chuang, Shu-Chun and Boeing, Heiner and Zuo, and Hui and Tell, Grethe S. and Pischon, Tobias and Jenab, Mazda and and Bueno-de-Mesquita, Bas and Vollset, Stein Emil and Midttun, Oivind and and Ueland, Per Magne and Fedirko, Veronika and Johansson, Mattias and and Weiderpass, Elisabete and Severi, Gianluca and Racine, Antoine and and Boutron-Ruault, Marie-Christine and Kaaks, Rudolf and Kuehn, Tilman and and Tjonneland, Anne and Overvad, Kim and Ramon Quiros, J. and Jakszyn, and Paula and Sanchez, Maria-Jose and Dorronsoro, Miren and Chirlaque, and Maria-Dolores and Ardanaz, Eva and Khaw, Kay-Tee and Wareham, Nicholas and J. and Travis, Ruth C. and Trichopoulou, Antonia and Lagiou, Pagona and and Trichopoulos, Dimitrios and Palli, Domenico and Sieri, Sabina and and Tumino, Rosario and Panico, Salvatore and May, Anne M. and Palmqvist, and Richard and Ljuslinder, Ingrid and Kong, So Yeon J. and Freisling, Heinz and and Gunter, Marc J. and Lu, Yunxia and Cross, Amanda J. and Riboli, Elio and and Vineis, Paolo", journal = "JNCI Journal of the National Cancer Institute", year = "2015", volume = "107", number = "4", publisher = "OXFORD UNIV PRESS INC", issn = "0027-8874, 1460-2105", doi = "10.1093/jnci/djv010", 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." }