MDM2 SNP309T>G Polymorphism with Hepatocellular Carcinoma Risk: A Meta-analysis

Abstract

The murine double minute 2 (MDM2) gene encodes a negative regulator of the tumor protein p53. A single nucleotide polymorphism (SNP) in MDM2 promoter, SNP309 T>G, has been reported to alter MDM2 protein expression and accelerate tumor formation in humans. Studies investigating the association between the polymorphism and human hepatocellular carcinoma (HCC) risk reported conflicting results. We performed a meta-analysis to explore the association of this polymorphism and HCC risk. All eligible studies published were searched for in PubMed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for the association using fixed- and random-effects models. We identified five case-control studies including 738 cases and 1014 controls for the present meta-analysis. In studies with limited data, we detected significant associations for all genetic models in the overall analysis (OR = 2.51, 95% CI = 1.88-3.36 for GG vs. TT, p <0.001, P(het) = 0.666; OR = 1.71, 95% CI = 1.35-2.18 for TG vs. TT, p <0.001, P(het) = 0.925; OR = 1.94, 95% CI = 1.54-2.43 for dominant model TG + GG vs. TT, p <0.001, P(het) = 0.772; OR = 1.74, 95% CI = 1.39-2.20 for recessive model GG vs. TT + TG, p <0.001, P(het) = 0.656). Moreover, in the subgroup analysis based on Hardy-Weinberg equilibrium (HWE) in controls, sample size, and ethnicity, significant associations were observed in most genetic models. This meta-analysis suggests that the MDM2 309 G allele probably acts as an important HCC risk factor. To further confirm our findings, well-designed studies with large sample sizes and representing different ethnicities are required.