Jin et al. Journal of Experimental & Clinical Cancer Research 2010, 29:18 http://www.jeccr.com/content/29/1/18 homozygotes had been diagnosed with HH and received treatment, such as venesection before developing LC or HCC, the conclusion that 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 popula- tions, 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 rela- tionship 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 gen- otype, 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 sub- group 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]. We noted that the power was satisfac- tory except when comparisons were performed between HCC cases and viral LC patients (power = 0.09). This indicated that the association of C282Y and HCC when compared in HCC cases and viral LC cases should be taken with caution and that it warranted further study in a larger scale. FPRP is a valuable criterion to assess whether or not a positive discovery came about by chance. We used FPRP to assess the positive association attained by this meta-analysis. The association between C282Y (Y vs. C) and HCC attained by subgroup analysis of four studies using alcoholic LC patients as controls was proved to be reliable (FPRP = 0.03). Population-attributable risk (PAR) is a valuable para- meter to assess the influence of risk factors on disease occurrence. The PAR of the variant allele Y of C282Y among alcoholic LC patients was 5.12% (95%CI: 2.57%- 7.67%). This result suggested that the role of C282Y polymorphism on HCC occurrence was modest. Conclusions This meta-analysis proved that C282Y mutation was associated with HCC in European alcoholic LC patients. The role of C282Y polymorphism on HCC occurrence was modest. The association of this polymorphism and Page 7 of 8 HCC is warranted further studies in large scale includ- ing diverse ethnicities. The molecular mechanism of the different effect of C282Y on alcoholic LC and viral LC, with respect to HCC occurrence, also merits further stu- dies. This meta-analysis did not find association of H63D mutation with HCC. Acknowledgements The present study was supported by the China Ministry of Health (2009ZX10004-301), National Natural Science Foundation (No. 30772505, No. 30872503 & No. 40830744), National Basic Research Program of China (2007CB936004) and China National Key Projects for Infectious Diseases (2008ZX10002-017). Authors’ contributions FJ participated in the design of the study and performed the statistical analysis. XZS conceived the study, participated in its design and coordination work, and helped draft the manuscript. LSQ helped search articles and revised the draft. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. 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