Abstract
BackgroundMDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including gastric cancer. Several studies were published to evaluate the association between SNP309 and gastric cancer risk. However, the results remain conflicting rather than conclusive.ObjectiveThe aim of this study was to assess the association between the MDM2 SNP309 polymorphism and gastric risk.MethodsWe performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively.ResultsFive published case-control studies, including 1,621 gastric cancer cases and 2,639 controls were identified. We found that the MDM2 SNP309 polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR = 1.54; 95%CI = 1.04–2.29, and GG versus GT/TT, OR = 1.49, 95%CI = 1.30–1.72). Furthermore, Egger's test did not show any evidence of publication bias (P = 0.799 for GG versus TT).ConclusionOur results suggest that the MDM2 SNP309 polymorphism may be a low-penetrant risk factor for the development of gastric cancer.
Highlights
Gastric cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death worldwide [1]
We found that the MDM2 SNP309 polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, Odds ratios (ORs) = 1.54; 95%confidence intervals (CIs) = 1.04–2.29, and GG versus GT/TT, OR = 1.49, 95%CI = 1.30–1.72)
Our results suggest that the MDM2 SNP309 polymorphism may be a low-penetrant risk factor for the development of gastric cancer
Summary
Gastric cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death worldwide [1]. Gastric cancer is a complex trait caused by both genetic and environmental factors [2]. In addition to above exogenous factors, genetic polymorphisms in the carcinogen detoxification, antioxidant protection, DNA repair and cell proliferation processes are crucial in the development of gastric cancer [4,5]. MDM2 is a crucial negative regulator of p53 through several mechanisms. MDM2 directly binds to p53, resulting in the inhibition of p53 transactivation activity [8]. MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including gastric cancer.
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