Published in:
Open Access
01-12-2013 | Research article
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
Authors:
Xiaolin Pan, Yuqin Li, Jin Feng, Xiaoyong Wang, Bo Hao, Ruihua Shi, Guoxin Zhang
Published in:
BMC Cancer
|
Issue 1/2013
Login to get access
Abstract
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.