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

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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.

Av författaren/redakt...: Stepien, Magdale ...; Hughes, David J.; Hybsier, Sandra; Bamia, Christina; Tjønneland, Anne; Overvad, Kim; visa fler...; Affret, Aurélie; His, Mathilde; Boutron-Ruault, ...; Katzke, Verena; Kuehn, Tilman; Aleksandrova, Kr ...; Trichopoulou, An ...; Lagiou, Pagona; Orfanos, Phlippo ...; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvator ...; Bueno-de-Mesquit ...; Peeters, Petra H ...; Weiderpass, Elis ...; Lasheras, Cristi ...; Bonet Bonet, Cat ...; Molina-Portillo, ...; Dorronsoro, Mire ...; Maria Huerta, Jo ...; Barricarte, Aure ...; 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; visa färre...

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