Jin et al. Journal of Experimental & Clinical Cancer Research 2010, 29:18 http://www.jeccr.com/content/29/1/18 Page 4 of 8 Figure 1 Forest plot of the RE ORs and 95% CIs of the association between HCC and the C282Y mutation (Y vs. C) of nine studies. The combined estimate is indicated by the diamond. The solid vertical line represents the result. (3) Meta-analysis of four studies that used viral LC patients as controls (including 160 case and 203 controls) showed both dominant model and allele contrast had a non-significantly decreased risk of HCC (FE OR = 0.70, 95%CI: 0.32-1.50 and FE OR = 0.71, 95%CI: 0.34-1.50, respectively). There was no small-study bias among stu- dies (Egger’s p = 0.51 and 0.52, respectively) and no het- erogeneity among studies (I2 = 0) (figure not shown). H63D Eight studies (included 958 cases and 2258 controls) provided H63D genotype data. Variant D allele fre- quency was 16.81% (322/1916) in cases and 14.32% (657/4516) in controls, respectively. Overall, this meta-analysis did not show H63D poly- morphisms had influence on HCC occurrence. FE OR was 1.19 (95%CI: 0.90-1.58, p for heterogeneity = 0.01, I2 = 0.60) and1.08 (95%CI: 0.83-1.39, p for heterogeneity = 0.01, I2 = 0.61) in the dominant model and allele con- trast model, respectively (figure not shown). There was no small-study bias among studies (Egger’s p = 0.62 and 0.34, respectively). We also performed subgroup meta- analysis according to the characteristics of controls (healthy controls and chronic liver diseases controls), but all genetic models did not show evidence of associa- tions with HCC (detailed data not shown). The statistic power is an important issue on gene-dis- ease association study. As for the association between C282Y polymorphism with HCC among alcoholic LC patients, we used the allele contrast (Y vs. C) data to calcu- late the power. According to the parameters (frequency of the mutation allele Y in the controls was 0.022, case num- ber was 224 and control number was 380, pooled OR was 3.41, a = 0.05), PS software gave a power of 0.82, which was satisfactory. However, power of the association study on HCC and viral LC patients (160 cases and 203 controls, frequency of variant allele Y = 0.05, pooled OR = 0.71, a = 0.05) was very low (0.09). By using the results of the meta-analysis (ORs and 95%CIs) and the knowledge of the epidemiological data of HCC (prior probability) in different populations, we Table 2 Meta-analysis results of C282Y polymorphism and HCC Nine studies of all samples Seven studies of healthy Four studies of alcoholic Four studies of viral LC controls LC Genetic model Dominant Allele contrast CY vs. CC Dominant Allele contrast Dominant Allele contrast Dominant Allele contrast OR 95%CI p for hetero I2 Egger’s p 1.43 0.98-2.07 0.02 0.55 0.31 1.50 1.05-2.14 0.02 0.57 0.39 1.31 0.89-1.95 0.02 0.56 0.99 1.46 0.96-2.22 0.04 0.54 0.97 1.61 1.08-2.39 0.04 0.55 0.65 4.06 2.08-7.92 0.77 0 0.25 3.41 1.81-6.41 0.47 0 0.43 0.70 0.32-1.50 0.47 0 0.51 0.71 0.34-1.50 0.49 0 0.52