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Stepien, Magdalena; Hughes, David J; Hybsier, Sandra; Bamia, Christina; Tjønneland, Anne; Overvad, Kim; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kühn, Tilman; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Phlippos; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvatore; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Lasheras, Cristina; Bonet Bonet, Catalina; Molina-Portillo, Elena; Dorronsoro, Miren; Huerta, José María; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Shungin, Dmitry; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Freisling, Heinz; Cross, Amanda J; Schomburg, Lutz; Jenab, Mazda
British journal of cancer, 02/2017, Volume: 116, Issue: 5Journal Article
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, P =0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P =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 =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.
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