From then on, several articles about HFE mutations and HCC have been published. learn more We selected nine eligible studies including 1102 cases and 3766 controls to conduct an updated meta-analysis. Because HH is more frequent in northern European populations, the studies on HFE gene mutations and HCC are mainly come from European ethnicities. In this meta-analysis, eight studies were come from Europe and one from Africa. So, the analysis results may be mainly applicable to European populations and it warrants to be studied in other ethnicities. In this meta-analysis, the frequency of C282Y YY homozygotes was 0.42%

(16/3766), and the frequency of CY heterozygotes was 9.32% (351/3766) in all control subjects. The genotype distribution was consistent with the dbSNP data. H63D genotype distribution was 2.66% (60/2258) and 23.78% (537/2258) for DD homozygotes and HD heterozygotes in controls, respectively. As to C282Y, the ORs of allele contrast (Y vs. C) in the six studies [8,

10–12, 15, 31] were larger than 1.0. Among the six studies, four studies [8, 10–12] reported a significant association between HCC and the C282Y polymorphism (ORs > 1.0, 95%CIs did not include 1.0). Because the frequency of the homozygous mutation of C282Y is very low, and a large proportion of C282Y homozygotes had been diagnosed with HH and received treatment, such as venesection before developing LC or HCC, the conclusion OSI-027 in vitro that Sitaxentan YY homozygotes increased HCC risk may have little clinical value. Thus, we only explored the dominant model and allele contrast in this meta-analysis. This meta-analysis proved that C282Y mutation was associated with HCC in European populations, especially in alcoholic LC patients but not in viral LC patients. This result is consistent

with the results of three previous studies [8, 15, 38], and it may implicate that the hepatocarcinogenesis of alcoholic LC and viral LC is different and warrants further study. Some studies explored the role of gender in the influence of the relationship between HFE gene and HCC [10, 14, 34] and found that C282Y homozygotes YY mutation increased the risk of HCC in male patients. One English study [10] reported that male C282Y homozygotes were more likely to be diagnosed with HCC (OR = 14, 95%CI: 5-37), and the penetrance of the C282Y homozygous genotype, with respect to HCC, was between 1.31% and 2.1% for males and zero for females. Another study [36] reported that C282Y homozygote males had a relative risk (RR) of about 23 for HCC occurrence, and the penetrance, with respect to HCC, was 5.56%. As there were few studies that provided concrete gender subgroup genotype values, we could not make a pooled analysis. From the pooled genotype data, we could assess the statistical power under various subgroup analyses using PS software [27].