MDM2 SNP309 variation contributes to leukemia risk: meta-analyses based on 7259 subjects

Evidence implicates MDM2 (murine double minute-2) T309G polymorphism as a risk factor for several cancers. Increasing numbers of studies have been carried out on the association of MDM2 T309G polymorphism with susceptibility to leukemia and have generated conflicting results. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of MDM2 T309G variation with leukemia were conducted. Separate analyses on ethnicity and clinical types were also performed. Eligible studies were identified for the period up to February 2012. Consequently, seven publications including eight case-control studies with 1777 cases and 5482 controls were selected for analysis. The overall data indicated a significant association of the MDM2 T309G polymorphism with leukemia risk (GG vs. TT: odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.14-2.29; dominant model: OR = 1.20; 95% CI = 1.06-1.36; recessive model: OR = 1.47; 95% CI = 1.07-2.03). In subgroup analysis by ethnicity, the G allele may increase leukemia susceptibility among Asians (GG vs. TT: OR = 3.06; 95% CI = 2.05-4.56; dominant model: OR = 1.82; 95% CI = 1.31-2.51; recessive model: OR = 2.32; 95% CI = 1.69-3.19) but not Caucasians. In subgroup analysis by clinical types, data suggested increased risk for acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) under additive and recessive models, respectively. Similarly, elevated risk for chronic lymphocytic leukemia (CLL) was shown under the dominant model. Collectively, the results of the present study suggest that MDM2 T309G polymorphism might be a low-penetrant risk factor for leukemia among Asians but not Caucasians. The G allele might increase CLL susceptibility and homozygous GG might elevate AML and CML risk.