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Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

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Title: Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
Authors: Stepien, M
Jenab, M
Freisling, H
Becker, N-P
Czuban, M
Tjonneland, A
Olsen, A
Overvad, K
Boutron-Ruault, M-C
Mancini, FR
Savoye, I
Katzke, V
Kuehn, T
Boeing, H
Iqbal, K
Trichopoulou, A
Bamia, C
Orfanos, P
Palli, D
Sieri, S
Tumino, R
Naccarati, A
Panico, S
Bueno-de-Mesquita, HBA
Peeters, PH
Weiderpass, E
Merino, S
Jakszyn, P
Sanchez, M-J
Dorronsoro, M
Huerta, JM
Barricarte, A
Boden, S
Van Guelpen, B
Wareham, N
Khaw, K-T
Bradbury, KE
Cross, AJ
Schomburg, L
Hughes, DJ
Item Type: Journal Article
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.
Issue Date: 1-Jun-2017
Date of Acceptance: 30-May-2017
URI: http://hdl.handle.net/10044/1/49536
DOI: https://dx.doi.org/10.1093/carcin/bgx051
ISSN: 1460-2180
Publisher: OUP
Start Page: 699
End Page: 707
Journal / Book Title: Carcinogenesis
Volume: 38
Issue: 7
Copyright Statement: © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
OXIDATIVE STRESS
TRACE-ELEMENTS
HEME IRON
DIAGNOSTIC-VALUE
HUMAN PHYSIOLOGY
SELENIUM STATUS
BREAST-CANCER
RECTAL-CANCER
SERUM
RATIO
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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