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

Magdalena Stepien, David J. Hughes, Sandra Hybsier, Christina Bamia, Anne Tjønneland, Kim Overvad, Aurélie Affret, Mathilde His, Marie Christine Boutron-Ruault, Verena Katzke, Tilman Kühn, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Phlippos Orfanos, Domenico Palli, Sabina Sieri, Rosario Tumino, Fulvio Ricceri, Salvatore PanicoH. B. Bueno-De-Mesquita, Petra H. Peeters, Elisabete Weiderpass, Cristina Lasheras, Catalina Bonet Bonet, Elena Molina-Portillo, Miren Dorronsoro, José María Huerta, Aurelio Barricarte, Bodil Ohlsson, Klas Sjöberg, Mårten Werner, Dmitry Shungin, Nick Wareham, Kay Tee Khaw, Ruth C. Travis, Heinz Freisling, Amanda J. Cross, Lutz Schomburg, Mazda Jenab

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)688-696
Number of pages9
JournalBritish Journal of Cancer
Volume116
Issue number5
DOIs
Publication statusPublished - Feb 28 2017

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Zinc
Copper
Hepatocellular Carcinoma
Urinary Bladder
Micronutrients
Biliary Tract
Neoplasms
Liver Neoplasms
Biliary Tract Neoplasms
Intrahepatic Bile Ducts
Case-Control Studies
Fluorescence
Odds Ratio
X-Rays
Confidence Intervals
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Stepien, M., Hughes, D. J., Hybsier, S., Bamia, C., Tjønneland, A., Overvad, K., ... Jenab, M. (2017). Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans. British Journal of Cancer, 116(5), 688-696. https://doi.org/10.1038/bjc.2017.1

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans. / 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.; 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.

In: British Journal of Cancer, Vol. 116, No. 5, 28.02.2017, p. 688-696.

Research output: Contribution to journalArticle

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 2017, 'Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans', British Journal of Cancer, vol. 116, no. 5, pp. 688-696. https://doi.org/10.1038/bjc.2017.1
Stepien M, Hughes DJ, Hybsier S, Bamia C, Tjønneland A, Overvad K et al. Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans. British Journal of Cancer. 2017 Feb 28;116(5):688-696. https://doi.org/10.1038/bjc.2017.1
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. ; 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. / Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans. In: British Journal of Cancer. 2017 ; Vol. 116, No. 5. pp. 688-696.
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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.",
author = "Magdalena Stepien and Hughes, {David J.} and Sandra Hybsier and Christina Bamia and Anne Tj{\o}nneland and Kim Overvad and Aur{\'e}lie Affret and Mathilde His and Boutron-Ruault, {Marie Christine} and Verena Katzke and Tilman K{\"u}hn and Krasimira Aleksandrova and Antonia Trichopoulou and Pagona Lagiou and Phlippos Orfanos and Domenico Palli and Sabina Sieri and Rosario Tumino and Fulvio Ricceri and Salvatore Panico and Bueno-De-Mesquita, {H. B.} and Peeters, {Petra H.} and Elisabete Weiderpass and Cristina Lasheras and {Bonet Bonet}, Catalina and Elena Molina-Portillo and Miren Dorronsoro and Huerta, {Jos{\'e} Mar{\'i}a} and Aurelio Barricarte and Bodil Ohlsson and Klas Sj{\"o}berg and M{\aa}rten Werner and Dmitry Shungin and Nick Wareham and Khaw, {Kay Tee} and Travis, {Ruth C.} and Heinz Freisling and Cross, {Amanda J.} and Lutz Schomburg and Mazda Jenab",
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T1 - Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

AU - Stepien, Magdalena

AU - Hughes, David J.

AU - Hybsier, Sandra

AU - Bamia, Christina

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Affret, Aurélie

AU - His, Mathilde

AU - Boutron-Ruault, Marie Christine

AU - Katzke, Verena

AU - Kühn, Tilman

AU - Aleksandrova, Krasimira

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Orfanos, Phlippos

AU - Palli, Domenico

AU - Sieri, Sabina

AU - Tumino, Rosario

AU - Ricceri, Fulvio

AU - Panico, Salvatore

AU - Bueno-De-Mesquita, H. B.

AU - Peeters, Petra H.

AU - Weiderpass, Elisabete

AU - Lasheras, Cristina

AU - Bonet Bonet, Catalina

AU - Molina-Portillo, Elena

AU - Dorronsoro, Miren

AU - Huerta, José María

AU - Barricarte, Aurelio

AU - Ohlsson, Bodil

AU - Sjöberg, Klas

AU - Werner, Mårten

AU - Shungin, Dmitry

AU - Wareham, Nick

AU - Khaw, Kay Tee

AU - Travis, Ruth C.

AU - Freisling, Heinz

AU - Cross, Amanda J.

AU - Schomburg, Lutz

AU - Jenab, Mazda

PY - 2017/2/28

Y1 - 2017/2/28

N2 - 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.

AB - 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.

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DO - 10.1038/bjc.2017.1

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