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 MC., 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 HB., 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 KT., 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.