• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5691-5694
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• 2012

Ectopic expression of CDX2 in the stomach is closely associated with chronic Helicobacter pylori (H. pylori) infection and intestinal metaplasia. Whether CDX2 has tumor suppression or tumorigenesis potential remains to be elucidated. In this study, we investigated the association between the CDX2 G543C polymorphism (silent mutation) and the risk for H. pylori-induced gastric atrophy and cancer as well as H. pylori infection, using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The frequency of the minor allele was the same as previously reported in China, but different from that reported in England. CDX2 G543C was not associated with risk of H. pylori infection, gastric atrophy, or gastric cancer, although the point estimate for non-cardiac differentiated gastric cancer as compared to controls with gastric atrophy was 2.22 (95%CI=0.17-29.4). In conclusion, our results indicate that the CDX2 G543C polymorphism is unlikely to affect the H. pylori infection-gastric atrophy-gastric cancer sequence.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5713-5718
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• 2013

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9905-9908
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• 2014

Background: Helicobacter pylori (H. pylori) is the most common chronic infectious agent in the stomach. Most importantly, it may lead to atrophy, metaplasia and cancer. The aim of this study was to investigate the incidence of H. pylori infection and to detect early mucosal changes that may lead to malignant degeneration in children. Materials and Methods: Children who underwent upper gastrointestinal endoscopy were included. Familial history of gastric cancer was noted. Endoscopic examinations were performed by a single pediatric gastroenterologist. A minimum of three biopsy samples were collected during endoscopy. The patients were accepted as H. pylori infected if results of biopsies and rapid urease test were both positive. Biopsies were evaluated for the presence and degree of chronic inflammation, the activity and severity of gastritis, glandular atrophy and intestinal metaplasia. Results: A total of 750 children (388 boys, 362 girls) were evaluated in our study, with a mean age of 10.1 years. A total of 390 patients (52%) were found to be infected with H. pylori. Among the H. pylori infected patients, 289 (74%) were diagnosed to have chronic superficial gastritis, 24 (6.2%) had gastric atrophy. Most strikingly, intestinal metaplasia was observed in 11 children, all were in the H. pylori positive group. There was no difference in the mean of age, gender and socioeconomic class between H. pylori infected and non-infected groups. The frequency of gastric cancer in family members (4 in number) was higher in patients with H. pylori infection. No gastric cancer case was reported from the parents of non-infected children. The worst biopsy parameters (atropy and metaplasia) were improved after H. pylori eradication on control endoscopy. Conclusions: The current study shows a higher prevalence of familial history of gastric cancer in H. pylori infected children. Intestinal metaplasia was also higher in the infected children. Eradication of H. pylori infection for this risk group may prevent subsequent development of gastric cancer.

• Clinical Endoscopy
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• v.56 no.1
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• pp.75-82
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• 2023

Background/Aims: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. Methods: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. Results: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). Conclusions: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.158-162
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• 2005

Purpose: In order to clarify the carcinogenesis mechanism from chronic atrophic gastritis toward gastric cancer, we measured the pepsinogen I and II and compared their ratio with several clinical findings. Materials and Methods: We measured the preoperative serum pepsinogen I and II by using a radio-immunoassay and compared their ratio with several clinical findings, such as tumor size, mucinous vs non-mucinous tumor, cell differentiation, tumor location, depth of invasion, lymph-node status, Lauren's classification, and peritumoral atrophy in 103 consecutive patients with gastric adenocarcinomas who had received resections at Bundang CHA Hospital during the period from July 2003 to February 2005. Results: There were significant differences in the serum pepsinogen I/II ratio between patients with mucinous vs non-mucinous tumors (n=4 vs 9 and mean pep I/II=1.29 vs. 2.99, p=0.0288), with tumor size more than and less than $10cm^2$ (n=55 vs. 48 and mean pep I/II=2.64 vs. 3.24, p=0.0491), and with or without peritumoral atrophy (n=94 vs. 9 and mean pep I/II=2.83 vs. 3.89, p=0.0466). In patients with peritomoral atrophy, the pepsinogen I/II ratio was also lower in larger tumors (n=48 vs. 46 and mean pep I/II=2.44 vs. 3.23, p=0.0083). Well-differentiated carcinomas showed significantly lower serum pep I/II ratios than signet-ring-ceil types. There was no correlation between serum pep I/II ratio and tumor location, depth of invasion, lymph-node status, or Lauren's classification Conclusion: We proved the existence of a correlation between serum pepsinogen level and musosal atrophy, but these results are not sufficient for clinical application of serum pepsinogen level as a screening tool for gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3549-3554
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• 2013

Background: It is generally accepted that gastric carcinomas are preceded by a sequential multistage process that includes chronic gastritis, gastric atrophy, usually with intestinal metaplasia (IM), and dysplasia. This series of changes in gastric carcinogenesis is often initiated by Helicobacter pylori (H pylori) infection. The aim of the present study was determination of gastric histopathologic changes in IM patients after at least one year in Guilan province, Iran. Materials and Methods: This case-series study was conducted in Guilan Gastrointestinal and Liver Disease Research Center (GLDRC) during 2010 to 2011. Gastric biopsy was performed for all 71 known cases of IM and precanceric lesions including gastric atrophy, IM, dysplasia and H pylori infection were determined after at least one year. Results: Of the total of 71 patients with established IM who were enrolled, 50 had complete-type IM and 21 had incomplete-type IM. Fifty two people had H pylori infection. H pylori eradication was achieved in 39 patients (75%). Secondary pathology findings of patients with IM were complete metaplasia (39.4%), incomplete metaplasia (32.4%), dysplasia (23.9%) and other precanceric lesions (4.2%). Dysplasia (20%vs 33%) occurred in patients who had complete and incomplete IM at baseline respectively (p>0.05). Age, gender, family history of gastric cancer(GC); smoking habits and NSAIDs use were not associated with gastric premalignant lesions in initial and secondary pathologies (p>0.05). The difference became statistically significant between H pylori infection in patients with more than 3 years diagnostic intervals (p<0.05). Statistical difference between eradicators and non-eradicators was not significant. Conclusions: We found that incomplete IM increased the risk of subsequent dysplasia in this study.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7911-7916
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• 2015

Serum anti-Helicobacter pylori antibodies and pepsinogens (PGs) have been used as gastric cancer screening and gastric mucosal status markers. Nepal is a low risk country for gastric cancer. However, the mountainous populace in the northern region culturally linked to Tibet as well as Bhutan, a neighboring country, have a high risk of GC. We collected gastric biopsy specimens and sera from 146 dyspeptic patients living in Kathmandu, Nepal. We also examined the sera of 80 volunteers living in the mountainous regions of the Himalayas. The optimal cut-off was calculated for serum biomarkers against the histology. Kathmandu patients (43.8%) were serologically positive for H. pylori infection, which was significantly lower than that for the mountainous (61.3%, P = 0.01). The same results also found in the prevalence of PG-positivity, PG I levels and PG I/II ratios (P = 0.001, P<0.0001 and P = 0.03, respectively). Moreover, the PG I/II ratios were significantly, and inversely correlated with the OLGA score (r = -0.33, P<0.009). The low incidence of gastric cancer in Nepal can be attributed to low gastric mucosal atrophy. However, the mountainous subjects have high-risk gastric mucosal status, which could be considered a high-risk population in Nepal.

• Journal of Gastric Cancer
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• v.16 no.3
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• pp.152-160
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• 2016

Purpose: Endoscopic diagnosis of gastric cancer (GC) that emerges after eradication of Helicobacter pylori may be affected by unique morphological changes. Using comprehensive endoscopic imaging, which can reveal biological alterations in gastric mucosa after eradication, previous studies demonstrated that Congo red chromoendoscopy (CRE) might clearly show an acid non-secretory area (ANA) with malignant potential, while autofluorescence imaging (AFI) without drug injection or dyeing may achieve early detection or prediction of GC. We aimed to determine whether AFI might be an alternative to CRE for identification of high-risk areas of gastric carcinogenesis after eradication. Materials and Methods: We included 27 sequential patients with metachronous GC detected during endoscopic surveillance for a mean of 82.8 months after curative endoscopic resection for primary GC and eradication. After their H. pylori infection status was evaluated by clinical interviews and $^{13}C$-urea breath tests, the consistency in the extension of corpus atrophy (e.g., open-type or closed-type atrophy) between AFI and CRE was investigated as a primary endpoint. Results: Inconsistencies in atrophic extension between AFI and CRE were observed in 6 of 27 patients, although CRE revealed all GC cases in the ANA. Interobserver and intraobserver agreements in the evaluation of atrophic extension by AFI were significantly less than those for CRE. Conclusions: We demonstrated that AFI findings might be less reliable for the evaluation of gastric mucosa with malignant potential after eradication than CRE findings. Therefore, special attention should be paid when we clinically evaluate AFI findings of background gastric mucosa after eradication (University Hospital Medical Information Network Center registration number: UMIN000020849).

• Journal of Gastric Cancer
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• v.15 no.4
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• pp.246-255
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• 2015

Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.

• 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.