Common variant on MDM2 contributes to endometrial cancer susceptibility: evidence based on 7 studies

Due to its important biological function as a key negative regulator of p53, the mouse double minute 2 homologue (MDM2) gene has been extensively studied. A functional variant in the MDM2 gene promoter, single-nucleotide polymorphism 309 (SNP309) T > G (rs2279744), has been reported to cause an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity, which may be associated with the development of cancer. A number of studies were performed to investigate the relationship between this SNP and endometrial cancer. But, the results remain controversial. Thus, we performed a comprehensive meta-analysis to derive a more precise estimation of this susceptibility. There were seven eligible articles with a total of 1,278 patients and 2,189 controls included in the meta-analysis. In the present study, we found significant associations under the allele contrast and recessive model. The G allele was associated with elevated risk for endometrial cancer [allele contrast OR = 1.33, 95 % confidence interval (CI) = 1.12-1.58, P(Z) = 0.0009, P(Q) = 0.02)], while the homozygous GG genotype may also increase the risk of endometrial cancer [OR = 1.88, 95 % CI = 1.40-2.52, P(Z) < 0.0001, P(Q) = 0.02]. In the subgroup analysis by ethnicity, we found similar significant results for both Caucasians [allele contrast OR = 1.41, 95 % CI = 1.04-1.92, P(Z) = 0.03, P(Q) = 0.001; recessive model OR = 1.89, 95 % CI = 1.10-3.23, P(Z) = 0.02, P(Q) = 0.002] and Asians [allele contrast OR = 1.24, 95 % CI = 1.01-1.53, P(Z) = 0.04, P(Q) = 0.86; recessive model OR = 1.75, 95 % CI = 1.24-2.45, P(Z) = 0.001, P(Q) = 0.75]. Overall, the meta-analysis demonstrated that the MDM2 SNP309 polymorphism may be associated with increased risk of endometrial cancer.