We have investigated the role of Helicobacter pylori infection and of other risk factors of gastritis and carditis in residents of a high-risk area for gastric cardia cancer. During a national population-based endoscopic survey, 508 randomly-selected participants aged > or =40 were enrolled. Mucosal biopsies were obtained from six standard sites. Polymorphonuclear (PMN) and mononuclear (MN) infiltration and combined inflammatory scores (CIS) for chronic gastritis and H.pylori were assessed. Relationships of H.pylori and reflux esophagitis with these variables were calculated for cardia and non-cardia subsites. Both PMN and MN infiltrations correlated strongly with H.pylori infection. For PMN the relationship was maximum for the antrum (odds ratio (OR) = 9.4 (5.2-17.1)) and minimum for the gastric body (OR = 1.7 (1.0-2.9)). There was a significant relationship between carditis and H.pylori (OR = 2.8 (1.7-4.9)). A similar relationship was obtained for MN infiltration. In 56% of subjects the mean MN score for the corpus was equal to or greater than that for the antrum. For 59% of subjects the MN score for the cardia was greater than or equal to the antral score. Use of logistic regression revealed that was the main risk factor for gastritis and carditis in all sites. There was an inverse relationship between reflux esophagitis and carditis. H.pylori is the main risk factor for gastritis for all sites of the stomach including the cardia; but this relationship is stronger for the antrum and cardia than for the body. Continuous cardia inflammation may contribute to the high incidence of gastric cardia cancer in this region.

To investigate the relationship between Helicobacter pylori (H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection.

One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pylori infection and p53 expressions were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26, D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were characterized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker.

H pylori infection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P = 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas. In those gastric carcinomas, the MSI-H frequency in H pylori-positive group was significantly higher than that in H pylori-negative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pylori-positive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups (P = 0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylori infection and no p53 expression could be seen in the H pylori-negative samples.

H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.

In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.

Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the chi2 test and the Fisher's exact test, respectively.

The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A-308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated.

The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.

To investigate the relationship between Helicobacter pylori (H.pylori) infection and the expressions of the p53, Rb, c-myc, bcl-2 and hTERT mRNA in a series of diseases from chronic gastritis (CG), intestinal metaplasia type I or II(IMI-II), intestinal metaplasia type III (IMIII), mild or modest dysplasia (DysI-II), severe dysplasia (DysIII) to gastric cancer(GC) and to elucidate the mechanism of gastric carcinogenesis relating to H.pylori infection.

272 cases between 1998 and 2001 were available for the study including 42 cases of CG, 46 cases of IMI-II, 25 cases of IMIII, 48 cases of DysI-II, 27 cases of DysIII, 84 cases of GC. H.pylori infection and the expressions of p53, Rb, c-myc, bcl-2 were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. HTERT mRNA was detected by in situ hybridization (ISH).

The expressions of p53, Rb, c-myc, hTERT mRNA and bcl-2 were higher in the GC than in CG, IM, Dys. The expression of c-myc was higher in IMIII with H.pylori infection (10/16) than that without infection (1/9) and the positive rate in DysI-II and DysIII with H.pylori infection was 18/30 and 13/17, respectively, higher than that without infection (4/18 and 3/10, respectively). In our experiment mutated p53 had no association with H.pylori infection, the expression of Rb was associated with H.pylori infection in GC, but the p53-Rb tumor-suppressor system abnormal in DysI-II cases, DysIII and GC cases with H.pylori infection was 21/30, 15/17 and 48/48 respectively, higher than non-infection groups (4/18, 3/10, 28/36). Furthermore the level of hTERT mRNA in GC with H.pylori infection (47/48) was higher than that without infection (30/36), however the relationship between bcl-2 and H.pylori was only in IMIII. C-myc had a close association with hTERT mRNA in DysIII and GC (P=0.0 253,0.0 305 respectively).

In the gastric carcinogenesis, H.pylori might cause the severe imbalance of proliferation and apoptosis in the precancerous lesions (IMIII and GysIII) first, leading to p53-Rb tumor-suppressor system mutation and telomerase reactivation, and finally causes gastric cancer.