Expression Pattern of Caspase 2 in Korean Gastric Cancers

PURPOSE: Caspase 2, a member of the family of ICE-like proteases, is activated by the Fas pathway and induces apoptosis by triggering the caspase cascade. The purpose of this study was to determine whether the expression pattern of caspase 2 might be associated with gastric cancer development and if so, to determine to which pathologic parameter it is linked. MATENRIALS AND METHODS: For the construction of the gastric cancer tissue microarray, 78 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of caspase 2 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. RESULTS: Caspase 2 was expressed on superficial and foveolar epithelial cells and lymphocytes in the gastric mucosa, mainly in cytoplasm. We found loss of caspase 2 expression in 41 (52.6%) of the 78 gastric cancer tissues. Statistically, histologic type and other pathologic parameters were not related with loss of caspase 2 expression. CONCLUSION: Our findings provide enough evidence that loss of caspase 2 expression may contribute to the development of Korean gastric cancer and that it might be one of the possible escape mechanisms from apoptosis in gastric cancer.

A Single Nucleotide Polymorphism in the E-cadherin Gene Promoter-160 is Not Associated with Risk of Korean Gastric Cancer

Recently, the -160 C/A polymorphism, located within the regulatory region of E-cadherin promoter, has been shown to influence E-cadherin transcription by altering transcription factor binding. We examined the effect of this polymorphism on risk of gastric cancer and on histological classification of intestinal- and diffuse-type gastric cancer in 146 normal healthy individuals and 292 Korean gastric cancer patients. Genomic DNA samples were examined by polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP)-sequencing and confirmed by restriction fragment length polymorphism (RFLP). Unexpectedly, there was no significant difference in the genotype frequencies of the polymorphism between normal control and gastric cancer patients (x(2) test, p=0.433). The estimated odd ratio of C/C to A/A genotype in gastric cancer cases was 1.07 (95% confidence interval, 0.396-2.870). We also found no evidence for differences in risk for the intestinal- and diffuse-type gastric cancer. These results suggest that the -160 C/A polymorphism of the E-cadherin has no direct effect on the risk of Korean gastric cancer development and on its histological classification.

Association of the Interleukin-1beta and Interleukin-1 Receptor Antagonist Genetic Polymorphism and Korean Gastric Cancer

PURPOSE: Interleukin 1beta (IL-1beta) polymorphisms are associated with hypochlorhydria, atrophic gastritis, and increased risk of gastric cancer in Caucasians. We tried to determine whether the IL-1beta and IL-1 receptor antagonist (IL-1 RN) genetic polymorphisms contribute to the development of gastric cancer and the specific type of gastritis in Korean. MATENRIALS AND METHODS: The study population was comprised of 128 gastric cancer patients with histologically proven carcinoma and 63 normal healthy individuals. Sixty-eight carcinomas were of intestinal-type and sixty tumors were of diffuse-type. No patient had a familial gastric cancer history. The 511 bp and 31 bp polymorphisms in the IL-1beta were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The polymorphism of the IL-1 RN was analyzed with variable number tandem repeat after PCR. RESULTS: The genotype of 511C/-31T of IL-1beta and allele 1 of IL-1 RN was dominant in the present subjects. The allelic frequencies of the C allele IL-1beta, which is a high risk genotype for gastric cancer, were 0.551 and 0.429 in gastric cancer and normal controls, respectively. Statistically, significant difference in allelic frequencies of three polymorphic sites between gastric cancer patients and normal controls, and between intestinal-type and diffuse-type was not observed. CONCLUSION: These results suggest that the polymorphisms of IL-1beta and IL-1 RN may not contribute to the development of Korean gastric caner and that other endogenous or exogenous factors will be important for gastric carcinogenesis.