Background: Common single‐nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three ...SNPs (rs11614913, rs2910164, and rs3746444) in pre‐miRNAs (miR‐196a2, miR‐146a, and miR‐499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori‐induced gastritis in Japanese population.
Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non‐cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non‐ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases.
Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non‐cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02–1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non‐cancer and non‐ulcer subjects (OR = 1.39, 95%CI = 1.00–1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09–2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non‐cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0–1 vs 2∼, adjusted OR = 1.62, 95%CI = 1.05–2.49, p =.03).
Conclusions: The rs2910164 (G>C) SNP in the miR‐146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR‐196a2 is associated with the degree of H. pylori‐induced mononuclear cell infiltration.
Background Magnifying narrow-band imaging (NBI) endoscopy visualizes superficial gastric mucosal and capillary patterns. We aimed to investigate changes in gastric mucosal patterns seen by magnifying ...NBI endoscopy after Helicobacter pylori eradication. Methods Gastric mucosal patterns in non-pathological gastric corpus were observed by magnifying NBI endoscopy before and 12 weeks after H. pylori eradication in thirty patients. By using paired photographs of each case, changes in NBI mucosal patterns during H. pylori eradication were judged in a consensus manner by three blinded endoscopists. Results At 12 weeks after H. pylori eradication, 20 of 24 subjects who had been successfully treated showed remarkable changes in gastric mucosal patterns (sensitivity 83.3%, specificity 100%). In the specimens from these subjects, the patterns of enlarged or elongated pits were improved to small oval or pinhole-like round pits, and the density of fine irregular vessels was decreased. Histological assessment showed alleviation of chronic inflammation in all subjects (p < 0.0001), while such a change was not observed for four subjects showing severe gastric atrophy and intestinal metaplasia. When the subjects were divided according to the presence of severe gastric atrophy, the diagnostic efficacy of magnifying NBI for predicting the results of H. pylori eradication was excellent in subjects without severe gastric atrophy and intestinal metaplasia (sensitivity and specificity, 100%). However, no change in the NBI mucosal pattern was observed in subjects with severe gastric atrophy and intestinal metaplasia, regardless of the H. pylori eradication result. Conclusions At least in subjects without severe gastric atrophy or intestinal metaplasia, successful H. pylori eradication treatment shows improvements in gastric mucosal patterns with the use of magnifying NBI endoscopy early after successful treatment.
Several study showed usefulness of microscopic capillaries, seen by magnifying narrow band imaging (NBI) endoscopy for predicting histopathology among superficial depressed or flat elevated gastric ...neoplasia (GN). Here we assessed the diagnostic efficacy of magnifying NBI for predicting histopathology among gastric protruding/or polypoid lesions.
Using endoscopic pictures of magnifying NBI from 95 protruding/or polypoid lesions (19 fundic gland polyps: FGP, 47 hyperplastic polyps: HP, and 29 GN), fine mucosal patterns were classified into four categories: small round, prolonged, villous or ridge, and unclear patterns, and micro vascular patterns were classified into five categories: honey comb, dense vascular, fine net work, core vascular, and unclear patterns.
Most suggestive micro vascular patterns for predicting FGP, and HP were honeycomb (sensitivity 94.7%, specificity 97.4%), and dense vascular patterns (sensitivity 93.6%, specificity 91.6%), respectively. Fine net work, core vascular, and unclear patterns presented higher specificity (97%, 100%, and 100%) for predicting GN, and diagnostic efficacy of combined of those patterns was favorable (sensitivity 86.2%, specificity 97.0%).
Micro vascular patterns by using magnifying NBI provides meaningful information for predicting the histopathology of gastric protruding/or polypoid lesions.
Combining the narrow-band imaging (NBI) system and magnifying endoscopy allows simple and clear visualization of microscopic structures of the superficial mucosa and its capillary patterns, which may ...be useful for precise endoscopic diagnosis in the gastrointestinal tract, being more closely to histopathological diagnosis. In the non-neoplastic gastric mucosa, there have been reports showing a potential usefulness of magnifying NBI for the diagnosis of Helicobacter pylori infection, degree of histological gastritis, and intestinal metaplasia. We have shown that magnifying NBI appearances in the non-neoplastic gastric mucosa also predicts pepsinogen levels, which indicates extension of gastric atrophy in the entire stomach, and gastric cancer occurrence. Furthermore, we have shown that magnifying NBI appearances predicts the result of H. pylori treatment. Clear visualization of fine mucosal and capillary patterns, obtained by magnifying NBI, allows prediction of the histological condition, more in detail without biopsy, and it may also be useful for less invasive, and cost-effective endoscopic gastric cancer surveillance, and prediction of H. pylori eradication.
Background
Early gastric cancer located from the pyloric ring to inside the duodenal bulb (DB) is not easily treated by endoscopic submucosal dissection (ESD). The endoscope needs to be reversed ...inside the DB to set the resection line at a safe distance from the anal side. Because of the space limitations and limited flexibility of conventional endoscopy (CE), there have been increasing possibilities of complications. Here we report a new ESD technique using a transnasal endoscope (TN-E) that is reversed inside the DB.
Methods
The subjects were 5 patients with early gastric cancer or adenoma, at locations ranging from the pyloric ring to inside the DB, who were all treated by ESD. We compared results in these patients (TN-E group) with results in five patients with similar disease characteristics who were treated by ESD before July 2008, when the TN-E treatment method was introduced (CE group). In the TN-E group, after marking by CE, we switched the endoscope to the TN-E, and performed the reversing procedure insidethe DB, and cut the anal side of the lesion in a semicircle. We switched back to CE to dissect the remaining half on the oral side. We compared the average resection time, en-bloc resection rate, and safety margin between the TN-E and CE groups.
Results
Reversing inside the DB and the anal-side procedures proved easy and there were no complications. No bleeding or perforation occurred. The average resection times and en-bloc resection rates were not different between the two groups. All the resections by the TN-E were more than 5 mm away from the tumor margin, whereas a resection rate with a safety margin of more than 5 mm was 80% by CE.
Conclusions
In conclusion, the TN-E was safe and effective for use inside the DB. ESD using the TN-E contributed to accurate pathological diagnosis, because the size of the resected specimen was sufficient to prevent the burning effect caused by the ESD.
Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major ...event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non‐neoplastic gastric mucosa.
Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP‐kinase and CDH1) loci, assessed by Methylation‐Specific‐Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated.
Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP‐kinase (adjusted OR = 0.30, 95%CI = 0.13–0.71, p = .0055) and CIHM high (OR = 0.42, 95%CI = 0.19–0.97, p = .04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p = .02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50 years and older generations (OR = 1.63, 95%CI = 1.01–2.62, p = .045).
Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP‐kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM‐related gastric carcinogenesis.
CpG island hypermethylation (CIHM) of tumor suppressor genes is one of the major events in the gastric carcinogenesis. We aimed to investigate the association between CIHM status of tumor suppressor ...genes and clinicopathological and morphological characteristics of gastric cancer.
CIHM of p14, p16, Death-associated protein kinase (DAPK) and E-cadherin (CDH1) genes were determined by methylation-specific-polymerase chain Reaction in 146 gastric cancer tissues. CIHM-high was defined as three or more methylated CpG islands.
CIHM pf p14 was found in 70 (47.9%) cases, in 26 (17.8%) for p16, in 104 (71.2%) for CDH1 and in 127 (87.0%) for DAPK. CIHM-high was also found in 63 cases (43.2%). No association was found between between CIHM status and different staging, Lauren's subtypes, anatomic location, venous and lymphatic invasion, lymph node metastasis, distant metastasis, or peritoneal dissemination. However, among early gastric cancer cases, the depressed type with ulceration presented a significantly lower prevalence of CIHM of DAPK. In addition, Borrmann type IV cases presented significantly lower prevalence of CIHM-high among advanced gastric cancer. The Borrmann type IV cases also presented lower mean methylation number.
The present results suggest that CIHM of DAPK and CIHM-high were associated with the morphological appearance of depressed type with ulceration in early gastric cancer, and Borrmann type IV advanced gastric cancer, respectively.
Introduction: A complex interaction of host genetic and environmental factors may be relevant in the development of Helicobacter pylori-related gastric diseases. Small, non-coding RNA molecules, ...called microRNAs (miRNAs), are thought to have functions as either tumor suppressors or oncogenes. Common single-nucleotide polymorphisms (SNPs) in miRNAs may change their property through altering miRNA expression and/or maturation, and thus they may have an effect on thousands of target mRNAs, resulting in diverse functional consequences. We evaluated the associations of three select SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (hsa-mir-196a2, hsa-mir-146a, and hsamir-499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of H. pylori-induced gastritis in central Japan. Methods: The rs11614913 (C > T), rs2910164 (G > C), and rs3746444 (A > G) SNPs were genotyped in a total of 1,249 subjects including 552 GC, 214 ulcer including 141 gastric ulcer (GU), 73 duodenal ulcer (DU), and 483 non-ulcer subjects. The degree of histological gastritis in the uninvolved mucosa was classified according to the updated Sydney System in 579 cases. The serum pepsinogen levels were measured by radioimmunoassay in 204 cases. Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non-cancer subjects (overall non-cancer vs. GC; adjusted OR = 1.30, 95%CI = 1.02-1.66, p = 0.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non-cancer and non-ulcer subjects (overall non-cancer vs. GC; adjusted OR = OR = 1.39, 95%CI = 1.00-1.93, p = 0.05, non-ulcer vs. GC; adjusted OR = 1.57, 95%CI = 1.09-2.27, p = 0.016). The rs2910164 CC genotype was associated with non-cardia (OR = 1.29, 95%CI = 1.01-1.64, p = 0.04) and upper-third anatomical locations (OR = 1.76, 95%CI = 1.02-3.02, p = 0.04), diffuse type histopathology (OR = 1.41, 95%CI = 1.01-1.96, p = 0.04), and advanced stage (OR = 1.56, 95%CI = 1.15-2.12, p = 0.004) compared to non-cancer subjects. In addition, the rs2910164 C carrier was associated with non-cardia (OR = 1.61, 95%CI = 1.11-2.34, p = 0.01) middle-third anatomical locations (OR = 1.62, 95%CI = 1.03-2.55, p = 0.04), and diffuse type histopathology (OR = 1.69, 95%CI = 1.02-2.79, p = 0.04) compared to non-ulcer subjects. The rs11614913 TT genotype was associated with a higher degree of mononuclear cell infiltration in the antrum by the Mann-Whitney U test (TT vs. others, 1.69 + or - 0.78 vs. 1.46 + or - 0.82. p = 0.002) and this association was confirmed by logistic regression analysis with adjustment for age, sex, and H. pylori infection (inflammation score 0-1 vs. 2-, OR = 1.62, 95%CI = 1.05-2.49, p = 0.03). No association was found between the three SNPs and risk of ulcer diseases and serum pepsinogen levels. Conclusions: The rs2910164 (G > C) SNP in the hsa-mir-146a is associated with susceptibility to GC. In addition, the rs11614913 (C > T) SNP in the hsa-mir-196a2 is associated with the degree of H. pylori-induced mononuclear cell infiltration. This is the first evidence that SNPs in the pre-miRNAs are associated with H. pylori-related gastric diseases in Japan.
Introduction: CpG island hyper methylation (CIHM) status provides a distinct clinicopathological feature of gastric cancer (GC). We investigated the association between the CIHM of four highly ...susceptible loci and GC. Methods: Paired samples of GC tissues and adjacent normal mucosa in GC patients as well as control samples from 180 non-GC subjects were obtained. CIHM of p14, p16, CDH1 and DAP-kinase (DAPK) genes were determined by Methylation Specific PCR. CIHM high was defined as when three or all CpG islands methylated. Result: Rates of CIHM of p14, CDH1, DAPK, and high CIHM in non-cancer mucosa were significantly higher in GC patients than in non-GC patients (p14: 32.2 vs. 50.4%; OR: 1.70, 95% CI 1.03-2.80, CDH1: 36.1 vs. 84.0%; OR: 8.65, 95% CI 14.74-15.77, DAPK: 42.2 vs. 83.2%; OR: 5.98, 95% CI 3.37-10.62 and high CIHM: 44.4 vs. 80.8%; OR: 4.40, 95% CI 2.51-7.72). CIHM in CDH1 and DAPK were associated with a greater risk of GC including all of its different subtypes. In comparison of a paired sample in GC patients, frequencies of CIHM of p16, CDH1, and high CIHM were decreased in cancer tissues than in normal mucosa. Mean methylation number in the cancer tissue was also decreased. Decreased CIHM of p14, CDH1, and high CIHM were associated with advanced stage, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination and distant metastasis. When dividing GC by mean methylation number into Type A (increased methylation number in GC tissues), Type B (no change in methylation number) and Type C (decreased methylation number in GC tissues), aggressive phenotypes of GCs presented lower prevalence of Type A, and higher prevalence of Type B and C. Conclusion: CIHM in non-neoplastic mucosa corresponded to a risk of GC, while it is suggested that CIHM may occur earlier in the gastric mucosa, then decrease during GC development and progression.
Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been shown to be associated with susceptibility to several types of human cancer. We evaluated the association between three ...SNPs (rs11614913, rs2910164 and rs3746444) in pre-miRNAs (miR-196a2, miR-146a and miR-499) and various clinicopathological characteristics, including CpG island hypermethylation (CIHM) status and overall survival in gastric cancer (GC) patients. rs11614913 (T>C), rs2910164 (C>G) and rs3746444 (A>G) SNPs were genotyped in 127 GC patients. CIHM of p14, p16, DAP-kinase and CDH1 genes was determined by methylation-specific polymerase chain reaction in the cancer tissues. A significant marginal association was found between the rs11614913 CC genotype and polypoid or elevated type morphology in early-stage GC (OR=6.29, 95% CI 1.18-33.47, p=0.03). The rs2910164 CC and CG genotypes were associated with increased susceptibility to CIHM of DAP-kinase (CC+CG, OR=5.48, 95% CI 1.30-23.10, p=0.02; CC, OR=6.93, 95% CI 1.37-35.02, p=0.02; CG, OR=4.24, 95% CI 0.87-20.78, p=0.07). The 11614913 TT and TC genotypes were associated with a higher number of CIHM (no. of CIHM 0-1 vs. 2-4; TT+TC, OR=3.67, 95% CI 0.98-13.72, p=0.05; TC, OR=4.08, 95% CI 1.04-15.97, p=0.04). When the subjects were divided according to age group, the combined rs11614913 TT+TC genotype tended to be associated with worse overall survival than the CC genotype in patients younger than 65 years of age (p=0.05). The combined rs2910164 CG+GG genotype also tended to be associated with worse overall survival than the CC genotype in the same age group (p=0.09). It appears that rs11614913 and rs2910164 SNPs in pre-miRNAs (miR-196a2 and miR-146a) affect the clinicopathological characteristics of GC, including its morphological appearance, CIHM status and overall survival.
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