PURPOSE: Recently the theory has been developed that host genetic factor affects interleukin (IL)-1beta might exert an influence on the divergent clinical outcomes. We evaluated the roles of H. pylori infection and polymorphism of IL-1beta in the carcinogenesis of gastric adenocarcinoma. METHODS: Gastric cancer tissues from 68 patients, peripheral blood from 43 controls, and various gastric cancer cell lines (MKN45, MKN74, SNU620, SNU638, SNU216, SNU601, and AGS) were used. Single nucleotide polymorphism (SNP) of IL-1beta-31 and the length of tandem repeat of IL-1RN were analyzed by PCR and automatic DNA sequencer. IL-1beta mRNA expressions from gastric cancer tissues were measured using semiquantitative RT-PCR and compared according to SNP of IL-1beta-31. We also investigated the IL-1beta-31 SNP from various cancer cell lines and measured IL-1beta mRNA and protein expressions using semiquantitative RT- PCR and ELISA. We constructed reporter systems for IL-1beta-31T/T and IL-1beta-31C/C and the responses to antigen PMA and H. pylori were compared. RESULTS: We couldn't find any significant difference in the frequencies of IL-1beta-31 SNP and IL-1RN polymorphism between the gastric cancer and control groups. IL-1beta mRNA and protein expression were significantly more highly responsive to PMA at IL-1beta-31 T/T type as compared with those of C/T or C/C type when studied in gastric cancer cell lines, although we couldn't find any significant difference of IL-1beta mRNA expression according to IL-1beta-31 SNP when studied in gastric cancer tissue. When we compared the activities of reporter systems, the basal luciferase activity, response to PMA, and response to H. pylori of reporter genes was 1.30-fold, 1.32-fold, and 1.62-fold higher respectively in pIL-1beta T/T type as compared with pIL-1beta C/C type. CONCLUSIONS: These findings indicate that SNP of IL-1beta exerts an influence on the expression of IL-1beta and there is a significant difference in response to environmental factors. They also suggest that the host with IL-1beta-31 T/T type has a higher risk of hypochlorhydria, gastric atrophy, and after all gastric cancer in response to H. pylori infection. However the relationship between polymorphism of IL-1beta and gastric adenocarcinoma require further study.
Achlorhydria ; Adenocarcinoma ; Atrophy ; Carcinogenesis ; Cell Line ; DNA ; Enzyme-Linked Immunosorbent Assay ; Genes, Reporter ; Helicobacter pylori* ; Helicobacter* ; Humans ; Interleukin-1beta* ; Interleukins ; Luciferases ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; RNA, Messenger ; Stomach Neoplasms* ; Tandem Repeat Sequences

PURPOSE: The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer. MATERIALS AND METHODS: We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23. RESULTS: The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC. CONCLUSION: Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.
Adenocarcinoma ; Gastrectomy ; Gastric Stump* ; Humans ; Lymph Nodes ; Male ; Multivariate Analysis ; Neoplasm Metastasis ; Stomach ; Stomach Neoplasms ; Survival Rate