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

Stepien M 1 , Hughes DJ 2 , Hybsier S 3 , Bamia C 4 , Tjønneland A 5 , Overvad K 6 Show all authors , Affret A 7 , His M 7 , Boutron-Ruault MC 7 , Katzke V 8 , Kühn T 8 , Aleksandrova K 9 , Trichopoulou A 10 , Lagiou P 10 , Orfanos P 10 , Palli D 11 , Sieri S 12 , Tumino R 13 , Ricceri F 14 , Panico S 15 , Bueno-de-Mesquita HB 16 , Peeters PH 17 , Weiderpass E 18 , Lasheras C 19 , Bonet Bonet C 20 , Molina-Portillo E 21 , Dorronsoro M 22 , Huerta JM 23 , Barricarte A 23 , Ohlsson B 24 , Sjöberg K 25 , Werner M 26 , Shungin D 27 , Wareham N 28 , Khaw KT 29 , Travis RC 30 , Freisling H 1 , Cross AJ 31 , Schomburg L 3 , Jenab M 1

Affiliations 

  • 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 Diet, Genes and Environment Unit, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark
  • 6 Department of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark
  • 7 Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, F-94805 Villejuif, France
  • 8 Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany
  • 9 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany
  • 10 Hellenic Health Foundation, Athens 115 27, Germany
  • 11 Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50139 Florence, Italy
  • 12 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
  • 13 Cancer Registry and Histopathology Unit, 'Civic-M.P.Arezzo' Hospital, ASP 97100 Ragusa, Italy
  • 14 Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, 10095 Turin, Italy
  • 15 Dipartamento di Medicina Clinicae Chirurgias, Federico II University, 80131 Naples, Italy
  • 16 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands
  • 17 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands
  • 18 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, N-9037 Tromsø, Norway
  • 19 Department of Functional Biology, Faculty of Medicine, University of Oviedo, CP 33006 Oviedo, Asturias, Spain
  • 20 Unit of Nutrition and Cancer.Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), 08908 Barcelona, Spain
  • 21 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18080 Granada, Spain
  • 22 Public Health Direction and Biodonostia Research Institute-Ciberesp Basque Regional Health Department, s/n 20014 San Sebastian, Spain
  • 23 Consortium for Biomedical Research in Epidemiology and Public Health (CIBER- CIBERESP), 28029 Madrid, Spain
  • 24 Department of Internal Medicine, Skåne University Hospital, Lund University, SE-205 92 Malmö, Sweden
  • 25 Department of Gastroenterology and Nutrition, Skåne University Hospital, Lund University, SE-205 92 Malmö, Sweden
  • 26 Department of Public Health and Medicine, Umeå University, SE-901 85 Umeå, Sweden
  • 27 Department of Public Health and Clinical Medicine and Institute of Odontology Umeå University, SE-901 85 Umeå, Sweden
  • 28 MRC Epidemiology Unit, University of Cambridge, CB2 0QQ Cambridge, UK
  • 29 Clinical Gerontology, School of Clinical Medicine, University of Cambridge, CB2 0QQ Cambridge, UK
  • 30 Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, OX3 7LF Oxford, UK
  • 31 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, W2 1NY London, UK
Br J Cancer, 2017 Feb 28;116(5):688-696.
PMID: 28152549 DOI: 10.1038/bjc.2017.1

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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