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

Stepien M, Hughes DJ, Hybsier S, Bamia C, Tjønneland A, Overvad K, et al.

Br J Cancer, 2017 Feb 28;116(5):688-696.
PMID: 28152549 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, 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.

Matched MeSH terms: Copper/blood*
Effects of different levels of dietary sulfur and molybdenum on concentrations of copper and other elements in plasma and liver of lambs fed palm kernel cake diets

Alimon AR, Ivan M, Jalaludin S

Br J Nutr, 2011 Oct;106(8):1224-30.
PMID: 21492494 DOI: 10.1017/S0007114511001462

A 6-month experiment with nine dietary treatments was conducted to determine amounts of S plus Mo supplements required to maintain normal hepatic concentrations of Cu and Mo and to prevent chronic Cu toxicity in lambs fed palm kernel cake (PKC) diets. All diets consisted of PKC supplemented with minerals and vitamins, and with appropriate amounts per kg DM of S (level 0 or level 1 = 1 g) as sodium sulfate and/or Mo (level 0; level 1 = 4 mg; level 2 = 8 mg; level 3 = 16 mg; level 4 = 32 mg) as ammonium molybdate to form treatments S0Mo1, S0Mo2, S0Mo3, S0Mo4, S1Mo0, S1Mo1, S1Mo2, S1Mo3 and S1Mo4.There was no effect (P>0·05) of dietary treatments on the growth performance of the lambs. The dietary supplement of 1 g S plus 8 mg Mo per kg dietary DM (treatment S1Mo2) prevented accumulation of Cu in the liver without elevation of the concentration of Mo (P>0·05). The treatments S0Mo1, S0Mo2 and S0Mo3 increased (P

Matched MeSH terms: Copper/blood
Fulltext Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Stepien M, Jenab M, Freisling H, Becker NP, Czuban M, Tjønneland A, et al.

Carcinogenesis, 2017 Jul 01;38(7):699-707.
PMID: 28575311 DOI: 10.1093/carcin/bgx051

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.

Matched MeSH terms: Copper/blood*
The effects of palm kernel cake based diet on spermatogenesis in Malin x Santa-Ines rams

Yaakub H, Masnindah M, Shanthi G, Sukardi S, Alimon AR

Anim. Reprod. Sci., 2009 Oct;115(1-4):182-8.
PMID: 19167847 DOI: 10.1016/j.anireprosci.2008.12.006

Testes from nine male Malin x Santa-Ines rams with an average body weight of 43.1+/-3.53 kg, were used to study the effects of palm kernel cake (PKC) based diet on spermatogenic cells and to assess copper (Cu) levels in liver, testis and plasma in sheep. Animals were divided into three groups and randomly assigned three dietary treatments using restricted randomization of body weight in completely randomized design. The dietary treatments were 60% palm kernel cake plus 40% oil palm frond (PKC), 60% palm kernel cake plus 40% oil palm frond supplemented with 23 mg/kg dry matter of molybdenum as ammonium molybdate [(NH(4))(6)Mo(7)O(24).4H(2)O] and 600 mg/kg dry matter of sulphate as sodium sulphate [Na(2)SO(4)] (PKC-MS) and 60% concentrate of corn-soybean mix+40% oil palm frond (Control), the concentrate was mixed in a ratio of 79% corn, 20% soybean meal and 1% standard mineral mix. The results obtained showed that the number of spermatogonia, spermatocytes, spermatids and Leydig cells were not significantly different among the three treatment groups. However, spermatozoa, Sertoli cells and degenerated cells showed significant changes, which, may be probably due to the Cu content in PKC. Liver and testis Cu levels in the rams under PKC diet was found to be significantly higher (P<0.05) than rams in Control and PKC-MS diets. Plasma Cu levels showed a significant increase (P<0.05) at the end of the experiment as compared to at the beginning of the experiment for PKC and Control. In conclusion, spermatogenesis is normal in rams fed the diet without PKC and PKC supplemented with Mo and S. However spermatogenesis was altered in the PKC based diet probably due to the toxic effects of Cu and the significant changes in organs and plasma. Thus, Mo and S play a major role in reducing the accumulation of Cu in organs.

Matched MeSH terms: Copper/blood