Correlations between MDM2 gene SNP309 polymorphism and susceptibility to leukemia

Abstract

Background: The objective of this study was to perform a systematic review of correlations between the single-nucleotide polymorphism at nucleotide 309 (single-nucleotide polymorphism, SNP309) in the murine double-minute 2 (MDM2) gene promoter and susceptibility to leukemia.

Material/methods: We performed a computer search of relevant case-control studies published from January 1990 to Jan 2014 in databases such as Ovid, EBSCO, PubMed, CNKI, CBMDISC, VIP, and WanFang Data. The literature was screened based on inclusion and exclusion criteria. The data were retrieved, and the quality of the methodology used in the studies was evaluated. A meta-analysis was performed by calculating the combined odds ratios (OR) and 95% confidence intervals (CI) using RevMan 5.0 and Stata 10.0 software. Sensitivity was analyzed and publication bias was assessed.

Results: A total of ten case-control studies from nine research papers were selected in this study, which included 1889 cases and 5707 controls. Meta-analysis showed that people who carried the G allele had increased susceptibility to leukemia compared to people who carried the T allele [OR=1.24, 95% CI (1.06, 1.45), P=0.007]. In a recessive model, the GG homozygotic population had a higher risk of leukemia than the heterozygotic GT+TT population [OR=1.47, 95% CI (1.11, 1.96), P=0.008]. We did not find significant difference in a dominant model [GG+GT vs. TT: OR=1.22, 95% CI (0.98, 1.52), P=0.07]. Publication bias was not significant.

Conclusions: SNP309 polymorphism in the MDM2 gene is associated with susceptibility to leukemia. The G allele may be a risk factor for leukemia.

Figure 1

Forest plot of leukemia susceptibility and SNP309 of MDM2 gene (a recessive model: GG vs. GT+TT), the horizontal lines correspond to the study-specific OR and 95% CI, respectively. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of OR and 95%CI.

Figure 2

Forest plot of leukemia susceptibility and SNP309 of MDM2 gene (a dominant model: TT vs. GG+GT), the horizontal lines correspond to the study-specific OR and 95% CI, respectively. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of OR and 95%CI.

Figure 3

Forest plot of leukemia susceptibility and SNP309 of MDM2 gene (an allele model: G vs. T), the horizontal lines correspond to the study-specific OR and 95% CI, respectively. The area of the squares reflects the study-specific weight. The diamond represents the pooled results of OR and 95%CI.

Figure 4

Begg’s funnel plot for publication bias tests. Each point represents a separate study for the indicated association. Log or represents natural logarithm of OR. Vertical line represents the mean effects size.