Association Of Gene Polymorphisms With Helicobacter Pylori Related Gastric Cancer In A Chinese Population

Background:This study examined single nucleotide polymorphisms and their associations with the risk of developing gastric cancer in relation to Helicobacter pylori infection in Chinese han population.Methods:We conducted a hospital-based case–control study including 296 incident gastric cancer patients and 160 gastritis controls. TagSNPs in PTPN11,NOD1,NOD2,CD14,TLR4,TLR9 genes were genotyped by using Sequenom MassArray system. Serum levels of anti-H.pylori IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. PCR-RFLP was also applied in genotyping P53Arg72Pro and MDM2 SNP T309G in 268 patients with gastric cancer , and 190 gender-age-matched chronic gastritis patients served as controls.Results:1. P53 Arg 72Pro and MDM2 SNPT309G are not associated the risk of gastric cancer.2. PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.3. The association of NOD1 and NOD2 polymorphisms and gastric cancer3.1 NOD1 rs2907749 GG genotype gene showed a decreased risk for gastric cancer [adjusted odds ratio (OR) 0.50; 95% confidence interval (CI) 0.26-0.95] while rs7789045 TT genotype showed an increased risk for gastric cancer (OR 2.14; 95%CI 1.20-3.82).3.2 An elevated risk of gastric cancer was observed in subjects with H.pylori infection and NOD1 rs7789045 TT genotype (OR 2.05; 95%CI 1.07-3.94) or NOD2 rs7205423 GC genotype (OR 2.52; 95%CI 1.05-6.04).3.3 Haplotype analysis suggested that the distribution of AGT (indicated as in the order of rs2907749, rs2075820 and rs7789045) in NOD1 between cases and control groups was significantly different (Pcorrected: 0.04).4. the association of TLR4 polymorphisms and gastric cancerTLR4 rs2149356 AC heterozygote genotype showed an elevated risk for gastric cancer (adjusted OR,1.55; 95%CI, 1.02-2.36; P= 0.042).An elevated risk for gastric cancer also was observed in subjects with rs7873784 CG heterozygote genotype and the recessive model (genotype CCvs. CG+GG) (adjusted OR,1.85; 95%CI, 1.01-3.37; P= 0.046 and OR, 1.88; 95%CI, 1.03-3.43; P= 0.039,respectively).5. the association of CD14 polymorphisms and gastric cancer5.1 CD14 rs2569190 the dominant model (GG+GA vs. AA)significantly decreased the risk of gastric cancer (adjusted OR,0.64; 95%CI,0.42-0.98 P=0.041;OR,0.64; 95%CI, 0.43-0.96 P=0.032,respectively).5.2 rs2563298,rs2569190,rs5744441 in CD14 constructed three haplotypes(CAC,CGT,AGC),The most common haplotype was CAC and the distribution was significantly different between cases and controls (P=0.048).Conclusions: P53 Arg 72Pro,MDM2 SNPT309G and PTPN11 G/A polymorphism at intron 3 could not infect the risk of gastric cancer. PTPN11 polymorphism was not associated with H.Pylori infection states in both cancer patients and controls.Genetic polymorphisms in NOD1,NOD2,TLR4,CD14 may interaction with H.pylori infection and may play important roles in developing gastric cancer in the Chinese population.