title: Common variant on MDM2 contributes to endometrial cancer susceptibility: evidence based on 7 studies.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 201999, People's Republic of China, yanzhao1011@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoer
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Hao
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Pan
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Jingwen
authors.initials: J
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Fang
authors.forename: Minghong
authors.initials: M
authors.lastname: Zhao
mesh_terms: D016889:Endometrial Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D017594:Publication Bias
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2