Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
Aged ; Female ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Intestinal Diseases/*genetics/microbiology/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions/metabolism/pathology ; Stomach Neoplasms/etiology/*genetics/microbiology

Epidemiological data including our studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer. However, this significant clinical outcome happens only in a small portion of infected person. This suggests that other contributors including host genetic and environmental factors might be involved in the disease process. Studies on the association between virulent strains of H. pylori and clinical outcomes failed to show significant results in Korea. Cytokine gene polymorphism such as interleukin-1 (IL-1) has been thought to play a role in gastric carcinogenesis. Our studies showed the controversial role of IL-1, TNF-A, IL-10 and IL-2 gene polymorphisms in the development of gastric cancer in Korea. Chronic infection and inflammation leading to tumorigenesis are mediated in part through the recognition of various stimuli by toll-like receptors (TLRs). Our studies on the polymorphisms of TLR4 and TLR2 showed no mutant form in Koreans. These discrepancies might reflect the genetic differences between Caucasians and Koreans or might be due to prevalent genetic polymorphisms with masked effect in gastric carcinogenesis in Koreans. As other candidate risk factors, there are constant or inconsistent results on the effect of dietary intake in gastric cancer. There are numerous similar risk for gastric carcinogenesis with different risk ratio including environmental factors in Caucasians and Koreans. Under the background of prevalent H. pylori infection and genetic polymorphisms, environmental factors including diet may potentiate their role in gastric carcinogenesis in Koreans.
Cytokines/genetics ; Diet ; Genetic Predisposition to Disease ; Helicobacter Infections/*complications/microbiology ; *Helicobacter pylori/pathogenicity ; Humans ; Korea ; *Polymorphism, Genetic ; Risk Factors ; Stomach Neoplasms/*etiology/genetics/microbiology ; Toll-Like Receptor 4/genetics ; Tumor Markers, Biological ; Virulence Factors

OBJECTIVETo study the expressions and the significance of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the remnant stomach.

METHODSFifty-eight patients with gastrectomy were examined by upper gastrointestinal endoscopy. Two biopsy specimens were obtained from the stoma and the upper corpus gastric mucosa in the remnant stomach. mRNA was extracted from biopsy specimens to measure the IL-8 and COX-2 gene mRNA levels by real-time PCR method.

RESULTSIL-8 and COX-2 levels were higher in stoma than in corpus, IL-8 levels in BI anastomosis were significantly higher in stoma than in corpus (P< 0.05). In Hp-negative patients, IL-8 and COX-2 levels in stoma were significantly higher in BII anastomosis than in BI anastomosis (P < 0.05). In Hp-positive patients, IL-8 and COX-2 levels in stoma showed no significant differences between BII anastomosis and BI anastomosis. In corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients, (P < 0.05), including in BI anastomosis and in BII anastomosis.

CONCLUSIONSThe risk of the secondary stomach carcinogenesis in stoma after distal gastrectomy is higher than that in corpus; The types of anastomosis may influence the risk for the secondary stomach carcinogenesis in the remnant stomach mucosa.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastric Mucosa ; metabolism ; microbiology ; Gastric Stump ; surgery ; Gastroenterostomy ; adverse effects ; methods ; Helicobacter Infections ; Helicobacter pylori ; Humans ; Interleukin-8 ; biosynthesis ; genetics ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthases ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Stomach Neoplasms ; etiology