An Updated Meta-Analysis on the Association of MDM2 SNP309 Polymorphism with Colorectal Cancer Risk

Abstract

BackgroundThe mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The 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 colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.MethodsAll studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsA total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055–1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106–1.404, P=0.000) and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037–1.311, P= 0.010). In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.ConclusionsThe present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

Impact of the Mdm2SNP309-G allele on a murine model of colorectal cancer

“…[33][34][35] Colons from AOM-treated age-matched Mdm2 SNP309-G/G mice had significantly reduced FoxO1 and FoxO3 protein levels when compared with Mdm2 SNP309-T/T mice (Figure 6a). Importantly, FoxO1 and FoxO3 mRNA levels were not significantly altered in the colons of these mice (Figure 6b), suggesting the difference in FoxO protein levels is mediated by posttranslational mechanisms, such as ubiquitination by Mdm2.…”

The RTEL1 rs6010620 Polymorphism and Glioma Risk: a Meta-analysis Based on 12 Case-control Studies

“…In addition, most studies involved only a few hundred glioma cases, which is too few to reliably assess genetic effects. Meta-analysis has been recognized as an important tool to precisely define the effect of selected genetic polymorphisms on disease risk and to identify potentially important sources of betweenstudy heterogeneity (Qin et al, 2013).…”

“…Gliomas account for approximately 80% of central nervous system malignant tumors and have a very poor prognosis (Schoemaker et al, 2010;Walsh et al, 2013b). Although the etiology of gliomas remains unclear, exposure to ionizing radiation has been identified as the only established risk factor (Little et al, 1998;Neglia et al, 2006).…”

Association between the MDM2 T309G Polymorphism and Leukemia Risk: a Meta-analysis

“…A functional single nucleotide polymorphism (SNP) in the promoter region of MDM2, SNP T309G (rs2279744), was reported to affect MDM2 expression levels. Individuals who carrying the GG genotype of the MDM2 SNP309 polymorphism were found to increase MDM2 expression and thereby attenuates p53 activity (Bond et al, 2004;Qin et al, 2013). The polymorphism of MDM2 T309G is suggested to be associated with the risk of various human cancers Gao et al, 2014;Tang et al, 2014;Wang et al, 2014).…”