Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 107, Issue 4, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djv010
Keywords
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Categories
Funding
- Research Council of Norway [204650]
- Europe Against Cancer Program of the European Commission (SANCO)
- Denmark: Danish Cancer Society
- France: Ligue centre le Cancer
- France: Institut Gustave Roussy
- France: Mutuelle Generale de l'Education Nationale
- France: Institut National de la Sante et de la Recherche Medicale (INSERM)
- Greece: the Hellenic Health Foundation
- Greece: Stavros Niarchos Foundation
- Greece: Hellenic Ministry of Health and Social Solidarity
- Germany: German Cancer Aid and Federal Ministry of Education and Research
- Italy: Italian Association for Research on Cancer and the National Research Council
- Netherlands: Dutch Ministry of Public Health, Welfare and Sports (VWS)
- Netherlands: Netherlands Cancer Registry (NKR)
- Netherlands: LK Research Funds
- Netherlands: Dutch Prevention Funds
- Netherlands: Dutch ZON (Zorg Onderzoek Nederland)
- Netherlands: World Cancer Research Fund (WCRF)
- Netherlands: Statistics Netherlands
- Norway: Helga - Nordforsk centre of excellence in food, nutrition and health
- Norway: Norwegian Extra Foundation for Health and Rehabilitation
- Norway: Norwegian Cancer Society
- Spain: Health Research Fund (FIS) of the Spanish Ministry of Health [Exp 96/0032, RETICC DR06/0020]
- Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia [6236]
- Navarra and the Catalan Institute of Oncology
- Sweden: Swedish Cancer Society
- Swedish Scientific Council
- Regional Governments of Skane and Vasterbotten
- United Kingdom: Cancer Research UK
- Medical Research Council
- Ministry of Public Health, Welfare and Sports
- Netherlands, German Cancer Aid
- Federal Ministry for Education and Research
- European Union
- AIRC-ITALY
- German Cancer Aid
- Stavros Niarchos Foundation
- Hellenic Ministry of Health
- Hellenic Health Foundation
- MRC
- Cancer Research UK
- National Cancer Institute [1RO1CA102460]
- Cancer Research UK [16491] Funding Source: researchfish
- Medical Research Council [MC_U106179471, G1000143, MC_UU_12015/1, G0401527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114, NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12015/1] Funding Source: UKRI
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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.
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