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

Magdalena Stepien, David J. Hughes, Sandra Hybsier, Christina Bamia, Anne Tjønneland, Kim Overvad, Aurélie Affret, Mathilde His, Marie Christine Boutron-Ruault, Verena Katzke, Tilman Kühn, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Phlippos Orfanos, Domenico Palli, Sabina Sieri, Rosario Tumino, Fulvio Ricceri, Salvatore PanicoH. B. Bueno-De-Mesquita, Petra H. Peeters, Elisabete Weiderpass, Cristina Lasheras, Catalina Bonet Bonet, Elena Molina-Portillo, Miren Dorronsoro, José María Huerta, Aurelio Barricarte, Bodil Ohlsson, Klas Sjöberg, Mårten Werner, Dmitry Shungin, Nick Wareham, Kay Tee Khaw, Ruth C. Travis, Heinz Freisling, Amanda J. Cross, Lutz Schomburg, Mazda Jenab

Research output: Contribution to journalArticlepeer-review

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, P trend =0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P trend =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, P trend =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.

Original languageEnglish
Pages (from-to)688-696
Number of pages9
JournalBritish Journal of Cancer
Volume116
Issue number5
DOIs
Publication statusPublished - Feb 28 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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