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

• Published in: British journal of cancer Vol. 116; no. 5; pp. 688 - 696
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2017; Nature Publishing Group; Cancer Research UK
• Subjects: 692/499; 692/699/67/1504/1610/4029; 692/699/67/2324; 692/700/139; Aged; Antioxidants; Associations; Bile ducts; Biliary Tract Neoplasms - epidemiology; Biomedical and Life Sciences; Biomedicine; Cancer and Oncology; Cancer och onkologi; Cancer Research; cancer risk factors; Carcinoma, Hepatocellular - epidemiology; Case-Control Studies; Clinical Medicine; Community medicine, Social medicine: 801; Copper; Copper - blood; Drug Resistance; Epidemiology; Europe - epidemiology; Female; Health sciences: 800; Helsefag: 800; Hepatitis; hepatocellular carcinoma; Humans; Klinisk medicin; Liver cancer; Liver Neoplasms - epidemiology; Male; Medical and Health Sciences; Medical disciplines: 700; Medical research; Medicin och hälsovetenskap; Medisinske Fag: 700; Middle Aged; Molecular Medicine; nested case-control study; Nutrition; Oncology; prospective cohort; Prospective Studies; Risk factors; Samfunnsmedisin, sosialmedisin: 801; VDP; zinc; Zinc - blood; Denmark; France; Sweden; copper; nested case–control study; prospective cohort; cancer risk factors; zinc; hepatocellular carcinoma
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2017.1

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, P trend =0.0123), but no association for copper (OR=1.06; 95% CI: 0.45–2.46, P trend =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 trend =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.