MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis

Qiliu Peng,Cuiju Mo,Xianjun Lao,Jingzhe Sui,Shi Yang,Aiping Qin,Limin Zhai,Xue Qin,Shan Li,Zhiping Chen,Junrong Wu

doi:10.1186/1756-9966-32-85

Abstract

ObjectiveThe SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and endometrial cancer risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association.MethodsAll studies published up to August 2013 on the association between MDM2 SNP309 polymorphism and endometrial cancer risk were identified by searching electronic databases PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM). The association between the MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsEight case–control studies with 2069 endometrial cancer cases and 4546 controls were identified. Overall, significant increase of endometrial cancer risk was found when all studies were pooled in the meta-analysis (GG vs. TT: OR = 1.464, 95% CI 1.246–1.721, P < 0.001; GG vs. TG + TT: OR = 1.726, 95% CI 1.251–2.380, P = 0.001; GG + TG vs. TT: OR = 1.169, 95% CI 1.048–1.304, P = 0.005). In subgroup analysis by ethnicity and HWE in controls, significant increase of endometrial cancer risks were observed in Caucasians and studies consistent with HWE. In subgroup analysis according to study quality, significant associations were observed in both high quality studies and low quality studies.ConclusionsThis meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility, especially in Caucasian populations. Further large and well-designed studies are needed to confirm this association.

Highlights

Endometrial cancer is one of the most common gynecologic cancers in developed countries [1,2]
Inclusion and exclusion criteria Studies included in the meta-analysis were required to meet the following criteria: (1) Case–control studies which evaluated the association between murine double minute-2 (MDM2) SNP309 polymorphism and endometrial cancer risk; (2) used an unrelated case–control design; (3) had an odds ratio (OR) with 95% confidence interval (CI) or other available data for estimating OR; and (4) the control population did not contain malignant tumor patients
Statistical analysis The strength of the association between MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) with 95% confidence intervals (CIs)

Summary

Introduction

Endometrial cancer is one of the most common gynecologic cancers in developed countries [1,2]. The murine double minute-2 (MDM2) is a key negative regulator of the P53 tumor suppressor pathway which has been suggested to be implicated in a variety of cancers [7]. Evidence shows that MDM2 can bind directly to P53 protein and inhibit its activity, resulting in its degradation via the ubiquitination pathway [8]. Individuals carrying the GG genotype of the MDM2 SNP309 polymorphism were found to have higher MDM2 levels, which led to attenuation of the TP53 pathway and acceleration of tumor formation in humans [9]. It was reported that the increase in MDM2 results in direct inhibition of p53 transcriptional activity, enabling damaged cells to escape the cell-cycle checkpoint and become carcinogenic [10]. It is biologically reasonable to hypothesize a potential relationship between the MDM2 SNP309 polymorphism and endometrial cancer risk

Methods

Results

Conclusion