Interaction of helicobacter pylori with genetic variants in the MDM2 promoter, is associated with gastric cancer susceptibility in Chinese patients

Abstract

Background and Aims: MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 (rs2279744) has been shown to increase the affinity of the transcriptional activator Sp1, resulting in elevated MDM2 transcription and expression in some cancers. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric cancer in Chinese patients. Methods: Two hundred and sixty patients with gastric cancer and 260 healthy controls were genotyped for MDM2 SNP309 using the PCR-RFLP method. Helicobacter pylori's infection status was determined using a validated serology test. Results: The healthy control group was found to be in Hard-Weinberg equilibrium at the polymorphic loci studied (κ2 = 3.63, p = 0.06). Multiple logistic regression analyses revealed that the risk of gastric cancer for SNP309 (G/G) was significantly increased when compared with T carriers (adjusted odds ratio (OR): 2.05, 95% confidence interval (CI): 1.31-3.20). Further stratification analyses based on the recessive models reveal that a significantly increased risk of gastric cancer associated with the GG genotype was evident among subjects with H. pylori infection (adjusted OR: 2.52, 95% CI: 1.45-4.37), and noncardia gastric cancer patients (adjusted OR: 2.29, 95% CI: 1.41-3.71), compared with the T carriers. When stratified by histologic subtype of gastric cancer, the risk was also statistically significant. There was no significant difference in age at diagnosis among genotypes. Conclusions: The MDM2 promoter SNP309 is associated with the presence of gastric cancer in Chinese patients especially those with H. pylori infection. © 2009 Blackwell Publishing Ltd.