Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.
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Authors
Stepien, Magdalena
Jenab, Mazda
Freisling, Heinz
Becker, Niels-Peter
Czuban, Magdalena
Tjønneland, Anne
Olsen, Anja
Overvad, Kim
Boutron-Ruault, Marie-Christine
Mancini, Francesca Romana
Savoye, Isabelle
Katzke, Verena
Kühn, Tilman
Boeing, Heiner
Iqbal, Khalid
Trichopoulou, Antonia
Bamia, Christina
Orfanos, Philippos
Palli, Domenico
Sieri, Sabina
Tumino, Rosario
Naccarati, Alessio
Panico, Salvatore
Bueno-de-Mesquita, HB As
Peeters, Petra H
Weiderpass, Elisabete
Merino, Susana
Jakszyn, Paula
Sanchez, Maria-Jose
Dorronsoro, Miren
Huerta, José María
Barricarte, Aurelio
Boden, Stina
van Guelpen, Behany
Wareham, Nick
Bradbury, Kathryn E
Cross, Amanda J
Schomburg, Lutz
Hughes, David J
Publication Date
2017-07-01Journal Title
Carcinogenesis
ISSN
0143-3334
Publisher
Oxford University Press (OUP)
Volume
38
Issue
7
Pages
699-707
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Stepien, M., Jenab, M., Freisling, H., Becker, N., Czuban, M., Tjønneland, A., Olsen, A., et al. (2017). Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.. Carcinogenesis, 38 (7), 699-707. https://doi.org/10.1093/carcin/bgx051
Abstract
Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.
Keywords
Aged, Biomarkers, Tumor, Case-Control Studies, Colorectal Neoplasms, Copper, Female, Humans, Male, Middle Aged, Oxidative Stress, Prospective Studies, Risk Factors, White People, Zinc
Sponsorship
Medical Research Council (G1000143)
Cancer Research Uk (None)
Medical Research Council (G0401527)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (MR/N003284/1)
Identifiers
External DOI: https://doi.org/10.1093/carcin/bgx051
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285537
Rights
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http://www.rioxx.net/licenses/all-rights-reserved
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