Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans.
Stepien M., Hughes DJ., Hybsier S., Bamia C., Tjønneland A., Overvad K., Affret A., His M., Boutron-Ruault M-C., Katzke V., Kühn T., Aleksandrova K., Trichopoulou A., Lagiou P., Orfanos P., Palli D., Sieri S., Tumino R., Ricceri F., Panico S., Bueno-de-Mesquita HBA., Peeters PH., Weiderpass E., Lasheras C., Bonet Bonet C., Molina-Portillo E., Dorronsoro M., Huerta JM., Barricarte A., Ohlsson B., Sjöberg K., Werner M., Shungin D., Wareham N., Khaw K-T., Travis RC., Freisling H., Cross AJ., Schomburg L., Jenab M.
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.