title: 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.
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.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Pan
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Feng
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Hao
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; C442865:lipopolysaccharide, Helicobacter pylori; D051736:Proto-Oncogene Proteins c-mdm2