Background: The incidence of primary liver cancer varies between countries. Many of the etiological factors contributing to the geographical variations in incidence are unknown. Development of hepatocellular carcinoma has been linked to levels of trace elements. This review summarizes the evidence associating HCC with trace elements.
Methods: MEDLINE, EMBASE, and CENTRAL databases were searched. Various inclusion and exclusion criteria were applied to select the articles for inclusion. Data extraction was performed using a custom designed data extraction form.
Results: A total of 12,344 references were identified. Duplicates, 1,597, were excluded. Clearly irrelevant references, 10,676, were excluded through reading titles and abstracts. Some references (59) were excluded by applying the exclusion criteria. Twelve studies including 646 patients and measuring iron content (8), copper content (11), zinc (9), and selenium (2) qualified for the review. Although a meta-analysis was not possible due to heterogeneity between the studies, a clear pattern of distribution of the trace elements was discernible.
Conclusion: Iron and zinc content are lower in HCC than in surrounding tissues or normal controls. Copper content is lower in HCC than in surrounding tissues and cirrhotic controls. Epidemiological and physiological reasons for the trace element alterations should be further investigated.