The Roles of Helicobacter pylori Infection and Interleukin-1beta Polymorphism in Gastric Cancer

ABSTRACT

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.