Aleksandrova Krasimira, Chuang Shu-Chun, Boeing Heiner, Zuo Hui, Tell Grethe S, Pischon Tobias, Jenab Mazda, Bueno-de-Mesquita Bas, Vollset Stein Emil, Midttun Øivind, Ueland Per Magne, Fedirko Veronika, Johansson Mattias, Weiderpass Elisabete, Severi Gianluca, Racine Antoine, Boutron-Ruault Marie-Christine, Kaaks Rudolf, Kühn Tilman, Tjønneland Anne, Overvad Kim, Quirós J Ramón, Jakszyn Paula, Sánchez María-José, Dorronsoro Miren, Chirlaque Maria-Dolores, Ardanaz Eva, Khaw Kay-Tee, Wareham Nicholas J, Travis Ruth C, Trichopoulou Antonia, Lagiou Pagona, Trichopoulos Dimitrios, Palli Domenico, Sieri Sabina, Tumino Rosario, Panico Salvatore, May Anne M, Palmqvist Richard, Ljuslinder Ingrid, Kong So Yeon J, Freisling Heinz, Gunter Marc J, Lu Yunxia, Cross Amanda J, Riboli Elio, Vineis Paolo
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrueke, Nuthetal, Germany (KA, HB); Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (SCC, BBdM, MJG, YL, AJC, ER, PV); Division of Health Policy Translation, Institutes of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan (SCC); Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway (HZ, GST); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine, Berlin-Buch, Germany (TP); International Agency for Research on Cancer, Lyon, France (MJe, SYJK, HF, MJo); National Institute for Public Health and the Environment, Bilthoven, the Netherlands (BBdM); Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands (BBdM); Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway (SEV); Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway (SEV); Bevital AS, Bergen, Norway (ØM); Section for Pharmacology, Department of Clinical Science, University of Bergen, Bergen, Norway (HZ, PMU); Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway (PMU); Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (VF); Winship Cancer Institute, Emory University, Atlanta, GA (VF); Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway (EW); Department of Research, Cancer Registry of Norway, Oslo, Norway (EW); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (EW); Samfundet Folkhälsan, Helsinki, Finland (EW); Human Genetics Foundation (HuGeF), Torino, Italy (GS, PV); Inserm, Centre for research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health team, F-94805, Villeju
J Natl Cancer Inst. 2015 Feb 23;107(4). doi: 10.1093/jnci/djv010. Print 2015 Apr.
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.
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.
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.
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.
新蝶呤可能与结直肠癌（CRC）的发生发展相关，它作为细胞免疫活性的生物标志物，对细胞衰老、氧化应激和炎症具有多效性作用。到目前为止，尚未在人群中评估诊断前新蝶呤与结肠癌和直肠癌风险之间的关联。
在欧洲癌症与营养前瞻性调查队列中进行了一项巢式病例对照研究，使用了830例新发CRC病例患者（561例结肠癌和269例直肠癌）血浆中总新蝶呤（T-N，新蝶呤和7,8-二氢新蝶呤之和）浓度的数据，这些病例患者在风险组内与830名对照参与者进行匹配。随后的一项重复研究使用了来自霍达兰健康研究的数据，在12年的随访期间，6594名健康参与者中有173例被诊断为CRC病例患者。
在对预先选定的CRC危险因素进行多变量调整后，发现T-N与CRC呈“U形”关联。与T-N分布的第二个五分位数相比，第一个、第三个、第四个和第五个五分位数的相对风险分别为2.37（95%CI = 1.66至3.39）、1.24（95%CI = 0.87至1.77）、1.55（95%CI = 1.08至2.22）和2.31（95%CI = 1.63至3.27）。在霍达兰健康研究中对这些关联的重复研究也得出了类似的结果。按结肠癌和直肠癌部位探索这些关联时未观察到差异（双侧P差异 = 0.87），并且在排除随访前四年内诊断的病例患者后也未观察到差异。
这些新发现提供了证据，证明诊断前T-N浓度所反映的细胞介导免疫抑制和激活在CRC发生发展中均发挥作用。
