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

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), intrahepati...

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Published inBritish 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
BACKGROUNDCopper 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.METHODSA 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.RESULTSFor 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.CONCLUSIONSZinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.
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 sub(trend)=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P sub(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 sub(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.
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.
Author Stepien, Magdalena
Orfanos, Phlippos
Wareham, Nick
His, Mathilde
Aleksandrova, Krasimira
Lasheras, Cristina
Schomburg, Lutz
Lagiou, Pagona
Weiderpass, Elisabete
Molina-Portillo, Elena
Khaw, Kay-Tee
Freisling, Heinz
Cross, Amanda J
Barricarte, Aurelio
Trichopoulou, Antonia
Overvad, Kim
Dorronsoro, Miren
Palli, Domenico
Tjønneland, Anne
Boutron-Ruault, Marie-Christine
Huerta, José María
Jenab, Mazda
Tumino, Rosario
Ricceri, Fulvio
Bonet Bonet, Catalina
Travis, Ruth C
Sjöberg, Klas
Katzke, Verena
Hybsier, Sandra
Affret, Aurélie
Sieri, Sabina
Bueno-de-Mesquita, H B(as)
Shungin, Dmitry
Hughes, David J
Kühn, Tilman
Werner, Mårten
Ohlsson, Bodil
Bamia, Christina
Peeters, Petra H
Panico, Salvatore
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Issue 5
Keywords copper
nested case–control study
prospective cohort
cancer risk factors
zinc
hepatocellular carcinoma
Language English
License From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0
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British Journal of Cancer
These authors contributed equally to this work.
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Snippet Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed...
Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess...
Background:Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to...
BACKGROUNDCopper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to...
Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed...
BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed...
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StartPage 688
SubjectTerms 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
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Title Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans
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