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, 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.

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

“…33 Further evidence suggests a link of elevated circulating copper with chronic inflammation and liver dysfunction. 21,34 In accordance with previous studies, serum copper levels were significantly higher in HCC patients with higher CRP level, higher Child-Pugh score, and higher liver damage score in the present study. The increase in circulating copper in HCC patients is likely due to the redistribution of copper in the body instead of increased copper intake.…”

“…Moreover, the changes in serum copper and zinc levels were increased with the severity of liver disease . Further evidence suggests a link of elevated circulating copper with chronic inflammation and liver dysfunction . In accordance with previous studies, serum copper levels were significantly higher in HCC patients with higher CRP level, higher Child‐Pugh score, and higher liver damage score in the present study.…”

“…Data from case–control studies indicate higher copper levels, lower zinc levels, or higher copper/zinc ratio in patients with various cancers, including HCC . Two nested case–control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort have observed that serum zinc levels were inversely and copper/zinc ratio was positively associated with risk of HCC and colorectal cancer, whereas higher serum copper levels were associated with increased risk of colorectal cancer, but not with risk of HCC . However, findings from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) showed no association between dietary intake of copper and zinc and liver cancer risk .…”

“…[15][16][17][18][19] Two nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort have observed that serum zinc levels were inversely and copper/zinc ratio was positively associated with risk of HCC and colorectal cancer, whereas higher serum copper levels were associated with increased risk of colorectal cancer, but not with risk of HCC. 20,21 However, findings from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) showed no association between dietary intake of copper and zinc and liver cancer risk. 22 With regard to cancer progression, data from a French cohort study and the National Health and Nutrition Examination Survey (NHANES) have linked higher serum levels of copper and lower zinc with increased overall cancer mortality.…”

Zinc enhances chemosensitivity to paclitaxel in PC‑3 prostate cancer cells

“…Zinc is an essential trace element for the function of ~200 enzymes in humans, thus serving an important role in genome stability and processes, including gene expression (9,20). Zinc concentrations have been demonstrated to be decreased by 60-70% in the serum and cancerous prostate tissue of patients with prostate cancer, and to decrease further as the cancer progresses (29). We speculate that the reduction in zinc concentration in prostate cancer may be associated with chemotherapy resistance.…”