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

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Item Type:	Article
Title:	A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
Creators Name:	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., Tjønneland, A., Overvad, K., Quirós, J.R., Jakszyn, P., Sánchez, M.J., Dorronsoro, M., Chirlaque, M.D., Ardanaz, E., Khaw, K.T., Wareham, N.J., Travis, R.C., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Palli, D., Sieri, S., Tumino, R., Panico, S., May, A.M., Palmqvist, R., Ljuslinder, I., Kong, S.Y.J., Freisling, H., Gunter, M.J., Lu, Y., Cross, A.J., Riboli, E. and Vineis, P.
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.
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
Source:	Journal of the National Cancer Institute
ISSN:	0027-8874
Publisher:	Oxford University Press
Volume:	107
Number:	4
Page Range:	djv010
Date:	April 2015
Official Publication:	https://doi.org/10.1093/jnci/djv010
PubMed:	View item in PubMed

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