• BMB Reports
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• v.36 no.1
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• pp.82-94
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• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7467-7472
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• 2013

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.78-87
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• 2009

Serum pepsinogen (sPG) is a marker of gastric mucosal atrophy, a condition that has been associated with an increased risk of gastric neoplasia. A low sPGI level and a low PG I/II ratio have been associated with severe gastric atrophy, and are frequently found in gastric cancer. Because the prevalence of gastric cancer is high in Korea, it would be convenient if a good biomarker for gastric cancer were developed. Two studies recently investigated the efficacy of sPG along with Helicobacter pylori (H. pylori) as a screening tool for gastric cancer. In these studies, sPG was measured using a Latex enhanced Turbidimetric Immunoassay. We found that H. pylori IgG status, age and gender were associated with serum pepsinogen levels. Thus, to increase the ability of the PG I/II ratio to detect atrophic gastritis, the cutoff value for the PG I/II ratio should be stratified according to the H. pylori IgG status. In addition, a PG I/II ratio ($\leq3.0$), which has been widely used as an international standard for gastric cancer, was found to be a reliable marker for the detection of gastric dysplasia or gastric cancer, especially of the intestinal type. The efficacy of the test in Korea was lower than the efficacy in Japan. However, the detecting power of a PG I/II ratio ($\leq3.0$) was significantly increased in the presence of H. pylori. The ratio together with H. pylori psotivitiy could provide a means of identifying persons at high risk of developing gastric cancer in Korea.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.167-171
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• 2009

Purpose: This study was done to determine the usefulness of serum pepsinogen (PG) levels as a screening method for gastric cancer, and to assess the relationships between serum PG and clinicopathologic factors of gastric adenocarcinoma. Materials and Methods: Serum PG concentrations were measured in 94 subjects who were classified into (a) a control group (50 subjects) without abnormal endoscopic finding on a health checkup, or (b) a gastric cancer group (44 subjects) who had surgery at Daegu Catholic University Hospital between Nov. 2008 and May 2009. Receiver operator characteristic curves were utilized to select the most suitable test. Using different cutoff points, sensitivity and specificity were calculated. We compared preoperative serum PG levels with several clinicopathologic findings for patients with gastric adenocarcinoma. Results: The Serum PG I：II ratio was the most useful as a screening test. The sensitivity and specificity of PG screening for gastric cancer were, respectively, 81.8% and 82%. The cut off point correlated with the type of intestinal cancer (Lauren classification; P=0.003), tumor stage (P=0.001), and gastric adenocarcinoma with peritumoral chronic atrophic gastritis (P=0.036). Conclusion: Serum PG levels were found to be a potentially useful screening test and to correlate with clinicopathologic factors in gastric cancer patients. But, in order to use serum PG found in a health checkup for gastric cancer as a clinical application a large scale study is recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.979-984
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• 2016

The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be strikingly lower than that in Japan. We conducted an on-site ecological study to investigate the association between the stomach cancer incidence and Helicobacter pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155 women) from the general population in Bali, Indonesia, we conducted a urea breath test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect chronic atrophic gastritis and urine analysis to estimate sodium and potassium excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and 7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0-3) for men and 3% (0-5) for women, significantly lower than the respective values in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4) for women, also significantly lower than the Japanese figures. Computed values for daily salt excretion were $13.3{\pm}4.1g$ (mean${\pm}$SD) for men and $11.1{\pm}3.1g$ for women, as high as corresponding Japanese consumption values. Moreover, the estimated potassium excretion was $3.2{\pm}0.7g$ for men and $2.8{\pm}0.6g$ for women in Bali, significantly higher than the figures in Japan. There were no associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be due to the rare H. pylori infection. Namely, the bacterium infection seems to be a critical factor for gastric cancer rather than host or other environmental factors.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1247-1251
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• 2012

Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

• Journal of Life Science
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• v.10 no.6
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• pp.630-639
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• 2000

The gastric pathogen Helicobacter pylori(H. pylori) establishes long-term chronic infection that can lead to atrophic gastritis, intestinal metaplasia, and gastric cancer. H. pylori, which express cytotoxic genes is now recohnized as a cause of peptic ulcer and is also a major risk factor for the development of gastric adenocarcinoma. We performed this study 1) to assess the detection rate of H. pylori according to direct investigation of bacteria of gastric biopsy specimen and two serologic tests of GAP test and Helico blot 2.0 system in the symptomatic and non-symptomatic group 2) to evaluate and compare the efficacy of two serologic tests of GAP test and Helico blot 2.0 system for the diagnosis of H. pylori infection. Forty-nine patients were positive for H pylori infection based on direct investigation of bacteria by histology. The detection rates of H. pylori infection based on direct investigation of bacteria by histology. The detection rates of H. phlori were significantly lower in gastric cancer than in other gastroduodenal disease(p<0.05). The concordance of two serologic tests of GAP test and Helico blot 2.0 system is poor. There was no statistically significant difference between the expression rate of CagA and VacA in the symptomatic and non-symptomatic group. Although Helico blot 2.0 system may not displace GAP test, it was a very sensitive serologic test for the diagnosis of H. pylori infection and it was used to detect IgG antibodies to H. pylori-specific antigens, including CagA, VacA and the various urease subunit. Our data suggest that further investigation is needed to determine whether or not the serologic expression of cytotoxic gene may be clinical usefulness of diagnostic methods in the gastroduodenal disease.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.904-908
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• 2005

Recently the pathological actions of CagA of Helicobacter pylori (H. pylori) on gastric epithelial cells have been reported. CagA is directly injected into the host cytoplasm and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes according to the amino acid sequence in the 3'region of CagA; i) the East Asian type (A-B-D of EPIYA motifs) and ii) the Western type (A-B-C of EPIYA motifs). Repeated EPIYA motifs in the 3'region of CagA are involved in the interaction with SHP-2. The East Asian type conferred stronger SHP-2 binding activity than the Westrrn type of CagA. Here we analyzed the amino acid sequences of the SHP-2 binding site of cagA gene in H. pyzori, and investigated whether there is my relationship between the diversities of cagA and the disease out-come in Korea. Most of Korean H. pylori strains showed A-B-D motifs(the East Asian type), and only one strain showed A-B-B-D motifs. In Korea, the incidence of atrophic gastritis and gastric cancer is significantly high compared with Western countries. The high frequency of the East Asian type CagA among Korean H. pylori strains would be involved in increasing the risk of gastric cancer in Korean populations.