Dietary intake and serum levels of copper and zinc and risk of hepatocellular carcinoma: A matched case-control study

Background: Copper and zinc are involved in the development of multiple malignancies; yet, epidemiological evidence on hepatocellular carcinoma (HCC) is limited. This study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of HCC. Methods: A total of 434 case-control pairs matched for sex and age (+/- 1 year) were included in this study. Cases with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort (GLCC) study, and healthy controls were from the Guangzhou Nutrition and Health Study (GNHS). A semi-quantitative 79-item food frequency questionnaire (FFQ) was used to assess habitual dietary intakes of copper and zinc. Serum levels of copper and zinc were measured by using inductively coupled plasma mass spectrometry. The copper (Cu)/ zinc (Zn) ratio was computed by dividing copper levels by zinc levels. Conditional logistic regression models were performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) for per 1 standard deviation increase (per-SD increase) in copper and zinc levels. Results: Higher dietary intake (ORper-SD increase = 0.65, 95% CI: 0.44, 0.96, P-trend = 0.029) and serum levels of zinc (ORper-SD increase = 0.11, 95% CI: 0.04, 0.30, P-trend <0.001) were both associated with a lower risk of HCC. Subgroup analyses showed that the inverse association was only pronounced in men but not in women (P-interaction = 0.041 for dietary zinc intake and 0.010 for serum zinc levels). Serum copper levels (ORper-SD increase = 2.05, 95% CI: 1.39, 3.03, P-trend = 0.020) and serum Cu/Zn ratio (ORper-SD increase = 6.53, 95% CI: 2.52, 16.92, P-trend<0.001) were positively associated with HCC risk, while dietary copper intake and dietary Cu/Zn ratio were not associated with HCC risk. Conclusion: Zinc may be a protective factor for HCC, especially among men, but the effects of copper on HCC risk are not clear.