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

M. Stepien, S. Hybsier, C. Bamia, A. Tjonneland, K. Overvad, A. Affret, M. His, M. C. Boutron-Ruault, V. Katzke, T. Kuhn, K. Aleksandrova, A. Trichopoulou, P. Lagiou, P. Orfanos, D. Palli, S. Sieri, R. Tumino, F. Ricceri, S. Panico, H. B. Bueno-de-MesquitaP. H. Peeters, E. Weiderpass, C. Lasheras, C. Bonet Bonet, E. Molina-Portillo, M. Dorronsoro, J. M. Huerta, A. Barricarte, B. Ohlsson, K. Sjoberg, M. Werner, D. Shungin, N. Wareham, K. T. Khaw, R. C. Travis, H. Freisling, A. J. Cross, L. Schomburg, M. Jenab

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28 Citations (Scopus)


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.

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.

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.

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
JournalBritish Journal of Cancer
Issue number5
Publication statusPublished - 02 Feb 2017


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