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Background  Studies on the association between  MDM2  SNP309 (T > G) and gastric cancer have reported conflicting results. Thus, the aim of this study was to investigate whether  MDM2  SNP309 is associated with susceptibility and prognosis of gastric carcinoma in Chinese patients.    Methods  Total of 574 gastric carcinoma cases and 574 age- and sex-matched healthy controls were included.  MDM2  polymorphism was detected by PCR- RFLP and infection of  Helicobacter pylori  ( H. pylori ) by a validated serology test. The functionality of  MDM2  SNP309, with or without  H. pylori  lipopolysaccharide (LPS), was examined by dual-luciferase assay. Kaplan-Meier survival curves were used to evaluate survival. Additional, a meta-analysis was conducted to verity the findings.    Results   MDM2  SNP309G/G genotype was associated with an increased risk of gastric carcinoma when compared with T/T genotype or T carriers (both  P  < 0.01), and a joint effect between  MDM2  SNP309G/G and  H. pylori  infection was observed to intensify gastric carcinoma risk. SNP309G/G was identified as an independent marker of poor overall survival of carcinoma. In vitro, the luciferase assay further showed an increased transcriptional activity of SNP309G allele compared with SNP309T allele, and the function of polymorphism T309G in  MDM2  gene promoter was intensified by  H. pylori  LPS. Pooled results from the meta-analysis confirmed that SNP309G/G genotype had a significantly increased risk of gastric carcinoma compared with T/T genotype or T carriers, consistent with the case–control findings.    Conclusions   MDM2  SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients. Additional, there is a joint effect of MDM2 SNP309G/G allele and  H. pylori  infection on gastric carcinoma development, which may attribute to  H. pylori  LPS.

bmc cancer

A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients