Interaction of Helicobacter pylori with Genetic Variants in the MDM2 Promoter, is Associated with Gastric CancerSusceptibility in Chinese Patients

摘要

Background and Aims: MDM2 is a major negative regulator of p53, and asingle nucleotide polymorphism (SNP) in the MDM2 promoter regionSNP309 (rs2279744) has been shown to increase the affinity of the tran-scriptional activator Spl, resulting in elevated MDM2 transcription andexpression in some cancers. The aim of this study was to determine whetherSNP309 is associated with susceptibility to gastric cancer in Chinese patients.Methods: Two hundred and sixty patients with gastric cancer and 260healthy controls were genotyped for MDM2 SNP309 using the PCR-RFLPmethod. Helicobacter pylori's infection status was determined using a vali-dated serology test. Results: The healthy control group was found to be in Hard—Weinberg equi-librium at the polymorphic loci studied (x2 = 3.63, p = 0.06). Multiple logis-tic regression analyses revealed that the risk of gastric cancer for SNP309(G/G) was significantly increased when compared with T carriers (adjustedodds ratio (OR): 2.05, 95% confidence interval (CI): 1.31-3.20). Furtherstratification analyses based on the recessive models reveal that a signifi-cantly increased risk of gastric cancer associated with the GG genotype wasevident 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 histologicsubtype of gastric cancer, the risk was also statistically significant. There wasno significant difference in age at diagnosis among genotypes. Conclusions: The MDM2 promoter SNP309 is associated with the presenceof gastric cancer in Chinese patients especially those with H. pylori infection.