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

M. Stepien; S. Hybsier; C. Bamia; A. Tjonneland; K. Overvad; A. Affret; M. His; M. C. Boutron-Ruault; V. Katzke; T. Kuhn; K. Aleksandrova; A. Trichopoulou; P. Lagiou; P. Orfanos; D. Palli; S. Sieri; R. Tumino; F. Ricceri; S. Panico; H. B. Bueno-de-Mesquita; P. H. Peeters; E. Weiderpass; C. Lasheras; C. Bonet Bonet; E. Molina-Portillo; M. Dorronsoro; J. M. Huerta; A. Barricarte; B. Ohlsson; K. Sjoberg; M. Werner; D. Shungin; N. Wareham; K. T. Khaw; R. C. Travis; H. Freisling; A. J. Cross; L. Schomburg; M. Jenab

doi:10.1038/bjc.2017.1

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

M. Stepien, S. Hybsier, C. Bamia, A. Tjonneland, K. Overvad, A. Affret, M. His, M. C. Boutron-Ruault, V. Katzke, T. Kuhn, K. Aleksandrova, A. Trichopoulou, P. Lagiou, P. Orfanos, D. Palli, S. Sieri, R. Tumino, F. Ricceri, S. Panico, H. B. Bueno-de-MesquitaP. H. Peeters, E. Weiderpass, C. Lasheras, C. Bonet Bonet, E. Molina-Portillo, M. Dorronsoro, J. M. Huerta, A. Barricarte, B. Ohlsson, K. Sjoberg, M. Werner, D. Shungin, N. Wareham, K. T. Khaw, R. C. Travis, H. Freisling, A. J. Cross, L. Schomburg, M. Jenab

School of Biological Sciences

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58 Citations (Scopus)

Abstract

ackground:
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.

Original language	English
Pages (from-to)	688-696
Journal	British Journal of Cancer
Volume	116
Issue number	5
DOIs	https://doi.org/10.1038/bjc.2017.1
Publication status	Published - 02 Feb 2017

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Stepien, M., Hybsier, S., Bamia, C., Tjonneland, A., Overvad, K., Affret, A., His, M., Boutron-Ruault, M. C., Katzke, V., Kuhn, T., Aleksandrova, K., Trichopoulou, A., Lagiou, P., Orfanos, P., Palli, D., Sieri, S., Tumino, R., Ricceri, F., Panico, S., ... 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

@article{0a72c23fafdd4ad3b3fe65fbd6d70e8e,

title = "Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans",

abstract = "ackground: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.",

author = "M. Stepien and S. Hybsier and C. Bamia and A. Tjonneland and K. Overvad and A. Affret and M. His and Boutron-Ruault, {M. C.} and V. Katzke and T. Kuhn and K. Aleksandrova and A. Trichopoulou and P. Lagiou and P. Orfanos and D. Palli and S. Sieri and R. Tumino and F. Ricceri and S. Panico and Bueno-de-Mesquita, {H. B.} and Peeters, {P. H.} and E. Weiderpass and C. Lasheras and {Bonet Bonet}, C. and E. Molina-Portillo and M. Dorronsoro and Huerta, {J. M.} and A. Barricarte and B. Ohlsson and K. Sjoberg and M. Werner and D. Shungin and N. Wareham and Khaw, {K. T.} and Travis, {R. C.} and H. Freisling and Cross, {A. J.} and L. Schomburg and M. Jenab",

year = "2017",

month = feb,

day = "2",

doi = "10.1038/bjc.2017.1",

language = "English",

volume = "116",

pages = "688--696",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "5",

}

Stepien, M, Hybsier, S, Bamia, C, Tjonneland, A, Overvad, K, Affret, A, His, M, Boutron-Ruault, MC, Katzke, V, Kuhn, 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, Sjoberg, 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

TY - JOUR

T1 - Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

AU - Stepien, M.

AU - Hybsier, S.

AU - Bamia, C.

AU - Tjonneland, A.

AU - Overvad, K.

AU - Affret, A.

AU - His, M.

AU - Boutron-Ruault, M. C.

AU - Katzke, V.

AU - Kuhn, T.

AU - Aleksandrova, K.

AU - Trichopoulou, A.

AU - Lagiou, P.

AU - Orfanos, P.

AU - Palli, D.

AU - Sieri, S.

AU - Tumino, R.

AU - Ricceri, F.

AU - Panico, S.

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

AU - Peeters, P. H.

AU - Weiderpass, E.

AU - Lasheras, C.

AU - Bonet Bonet, C.

AU - Molina-Portillo, E.

AU - Dorronsoro, M.

AU - Huerta, J. M.

AU - Barricarte, A.

AU - Ohlsson, B.

AU - Sjoberg, K.

AU - Werner, M.

AU - Shungin, D.

AU - Wareham, N.

AU - Khaw, K. T.

AU - Travis, R. C.

AU - Freisling, H.

AU - Cross, A. J.

AU - Schomburg, L.

AU - Jenab, M.

PY - 2017/2/2

Y1 - 2017/2/2

N2 - ackground: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.

AB - ackground: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.

U2 - 10.1038/bjc.2017.1

DO - 10.1038/bjc.2017.1

M3 - Article

SN - 0007-0920

VL - 116

SP - 688

EP - 696

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 5

ER -

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

Abstract

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