Dataset Information

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

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.

SUBMITTER: Stepien M

PROVIDER: S-EPMC5344297 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Stepien Magdalena M Hughes David J DJ Hybsier Sandra S Bamia Christina C Tjønneland Anne A Overvad Kim K Affret Aurélie A His Mathilde M Boutron-Ruault Marie-Christine MC Katzke Verena V Kühn Tilman T Aleksandrova Krasimira K Trichopoulou Antonia A Lagiou Pagona P Orfanos Phlippos P Palli Domenico D Sieri Sabina S Tumino Rosario R Ricceri Fulvio F Panico Salvatore S Bueno-de-Mesquita H B As HB Peeters Petra H PH Weiderpass Elisabete E Lasheras Cristina C Bonet Bonet Catalina C Molina-Portillo Elena E Dorronsoro Miren M Huerta José María JM Barricarte Aurelio A Ohlsson Bodil B Sjöberg Klas K Werner Mårten M Shungin Dmitry D Wareham Nick N Khaw Kay-Tee KT Travis Ruth C RC Freisling Heinz H Cross Amanda J AJ Schomburg Lutz L Jenab Mazda M

British journal of cancer 20170202 5

<h4>Background</h4>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.<h4>Methods</h4>A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutr ...[more]

PMID: 28152549

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Project description:BackgroundChronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers.MethodsWe obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy.ResultsAfter the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10-4 ≤ P < 0.05).ConclusionOur study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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