The EPIC-Norfolk Study
Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans.
British journal of cancer 2016 ; 116: 688-696.
Stepien M, Hughes DJ, Hybsier S, Bamia C, Tjønneland A, Overvad K, Affret A, 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, Molina-Portillo E, Dorronsoro M, Huerta JM, Barricarte A, Ohlsson B, Sjöberg K, Werner M, Shungin D, Wareham NJ, Khaw KT, Travis RC, Freisling H, Cross AJ, Schomburg L, and Jenab M
DOI : 10.1038/bjc.2017.1
PubMed ID : 28152549
PMCID : PMC5344297
Abstract
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.