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Br J Cancer. 2017 Feb 28;116(5):688-696. doi: 10.1038/bjc.2017.1. Epub 2017 Feb 2.

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans.

Author information

1
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 39372 Lyon Cedex 08, France.
2
Department of Physiology and Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
3
Institut for Experimental Endocrinology, Charité-Universitatsmedizin Berlin, 13353 Berlin, Germany.
4
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens 115 27, Germany.
5
Hellenic Health Foundation, Athens 115 27, Germany.
6
Diet, Genes and Environment Unit, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
7
Department of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark.
8
Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, F-94805 Villejuif, France.
9
Institut Gustave Roussy F-94805 Villejuif, France.
10
Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
11
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
12
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology, Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens 115 27, Germany.
13
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50139 Florence, Italy.
14
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
15
Cancer Registry and Histopathology Unit, 'Civic-M.P.Arezzo' Hospital, ASP 97100 Ragusa, Italy.
16
Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, 10095 Turin, Italy.
17
Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
18
Dipartamento di Medicina Clinicae Chirurgias, Federico II University, 80131 Naples, Italy.
19
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.
20
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK.
21
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
22
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands.
23
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, The School of Public Health, Imperial College, W2 1NY London, UK.
24
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, N-9037 Tromsø, Norway.
25
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, NO-0304 Oslo, Norway.
26
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 Stockholm, Sweden.
27
Genetic Epidemiology Group, Folkhälsan Research Center, 00250 Helsinki, Finland.
28
Department of Functional Biology, Faculty of Medicine, University of Oviedo, CP 33006 Oviedo, Asturias, Spain.
29
Unit of Nutrition and Cancer.Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), 08908 Barcelona, Spain.
30
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18080 Granada, Spain.
31
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER- CIBERESP), 28029 Madrid, Spain.
32
Public Health Direction and Biodonostia Research Institute-Ciberesp Basque Regional Health Department, s/n 20014 San Sebastian, Spain.
33
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, E-30008 Murcia, Spain.
34
Navarra Public Health Institute, Pamplona, Spain.
35
Navarra Institute for Health Research (IdiSNA), 31003 Pamplona, Spain.
36
Department of Internal Medicine, Skåne University Hospital, Lund University, SE-205 92 Malmö, Sweden.
37
Department of Gastroenterology and Nutrition, Skåne University Hospital, Lund University, SE-205 92 Malmö, Sweden.
38
Department of Public Health and Medicine, Umeå University, SE-901 85 Umeå, Sweden.
39
Department of Public Health and Clinical Medicine and Institute of Odontology Umeå University, SE-901 85 Umeå, Sweden.
40
MRC Epidemiology Unit, University of Cambridge, CB2 0QQ Cambridge, UK.
41
Clinical Gerontology, School of Clinical Medicine, University of Cambridge, CB2 0QQ Cambridge, UK.
42
Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, OX3 7LF Oxford, UK.

Abstract

BACKGROUND:

Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.

METHODS:

A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.

RESULTS:

For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.

CONCLUSIONS:

Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

PMID:
28152549
PMCID:
PMC5344297
DOI:
10.1038/bjc.2017.1
[Indexed for MEDLINE]
Free PMC Article

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