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Endoscopy is widely applied in the examination of gastric cancer. However, extensive knowledge and experience are required, owing to the need to examine the lesion while manipulating the endoscope. Various diagnostic support techniques have been reported for this examination. In our previous study, segmentation of invasive areas of gastric cancer was performed directly from endoscopic images and the detection sensitivity per case was 0.98. This method has challenges of false positives and computational costs because segmentation was applied to all healthy images that were captured during the examination. In this study, we propose a cascaded deep learning model to perform categorization of endoscopic images and identification of the invasive region to solve the above challenges. Endoscopic images are first classified as normal, showing early gastric cancer and showing advanced gastric cancer using a convolutional neural network. Segmentation on the extent of gastric cancer invasion is performed for the images classified as showing cancer using two separate U-Net models. In an experiment, 1208 endoscopic images collected from healthy subjects, 533 images collected from patients with early stage gastric cancer, and 637 images from patients with advanced gastric cancer were used for evaluation. The sensitivity and specificity of the proposed approach in the detection of gastric cancer via image classification were 97.0% and 99.4%, respectively. Furthermore, both detection sensitivity and specificity reached 100% in a case-based evaluation. The extent of invasion was also identified at an acceptable level, suggesting that the proposed method may be considered useful for the classification of endoscopic images and identification of the extent of cancer invasion. [ABSTRACT FROM AUTHOR]

Upper gastrointestinal endoscopy is widely performed to detect early gastric cancers. As an automated detection method for early gastric cancer from endoscopic images, a method involving an object detection model, which is a deep learning technique, was proposed. However, there were challenges regarding the reduction in false positives in the detected results. In this study, we proposed a novel object detection model, U-Net R-CNN, based on a semantic segmentation technique that extracts target objects by performing a local analysis of the images. U-Net was introduced as a semantic segmentation method to detect early candidates for gastric cancer. These candidates were classified as gastric cancer cases or false positives based on box classification using a convolutional neural network. In the experiments, the detection performance was evaluated via the 5-fold cross-validation method using 1208 images of healthy subjects and 533 images of gastric cancer patients. When DenseNet169 was used as the convolutional neural network for box classification, the detection sensitivity and the number of false positives evaluated on a lesion basis were 98% and 0.01 per image, respectively, which improved the detection performance compared to the previous method. These results indicate that the proposed method will be useful for the automated detection of early gastric cancer from endoscopic images. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Methods 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. Results 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%). Conclusion Micro vascular patterns by using magnifying NBI provides meaningful information for predicting the histopathology of gastric protruding/or polypoid lesions.

Gastrointestinal endoscopy is widely conducted for the early detection of gastric cancer. However, it is often difficult to detect early gastric cancer lesions and accurately evaluate the invasive regions. Our study aimed to develop a detection and segmentation method for early gastric cancer regions from gastrointestinal endoscopic images. In this method, we first collected 1208 healthy and 533 cancer images. The gastric cancer region was detected and segmented from endoscopic images using Mask R-CNN, an instance segmentation method. An endoscopic image was provided to the Mask R-CNN, and a bounding box and a label image of the gastric cancer region were obtained. As a performance evaluation via five-fold cross-validation, sensitivity and false positives (FPs) per image were 96.0% and 0.10 FP/image, respectively. In the evaluation of segmentation of the gastric cancer region, the average Dice index was 71%. These results indicate that our proposed scheme may be useful for the detection of gastric cancer and evaluation of the invasive region in gastrointestinal endoscopy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate whether single nucleotide polymorphisms in the DNMT3A gene are associated with susceptibility to gastric cancer in the Japanese population. The present case-control study examined the associations between single nucleotide polymorphisms (rs6733868 and rs13428812) in DNMT3A and cancer susceptibility in 343 patients with gastric cancer and 708 subjects without gastric malignancies on upper gastro-duodenal endoscopy. Of 708 controls, 409 were classified into two groups histologically: 99 cases with and 310 cases without gastric mucosal atrophy. Overall, homozygosity for the DNMT3A rs6733868 minor allele was significantly associated with a reduced risk of gastric cancer (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.402–0.958; P=0.031), especially of the intestinal type (OR, 0.494; 95% CI, 0.274–0.890; P=0.019). In subjects >60 years, rs6733868 minor allele homozygosity was significantly associated with gastric cancer susceptibility. Carriers of the rs6733868 minor allele had a reduced risk of severe gastric mucosal atrophy (OR, 0.495; 95% CI, 0.299–0.826; P=0.0069). In addition, the number of minor alleles of both rs6733868 and rs13428812 was significantly correlated with the risk of Helicobacter pylori (HP) infection (P=0.0070 and P=0.0050, respectively). However, rs13428812 was not associated with severe gastric mucosal atrophy or gastric carcinogenesis. The present results suggest that DNMT3A polymorphisms serve roles in the progression from HP infection to gastric mucosal atrophy and gastric carcinogenesis in terms of degree and manner. [ABSTRACT FROM AUTHOR]

Both genetic and epigenetic abnormalities play important roles in gastric cancer (GC) development. We investigated whether the molecular subtypes of gastric cancer by combining genetic and epigenetic anomalies define its clinicopathological features and prognosis. The CpG island methylator phenotype (CIMP), MLH1 methylation, TP53, and KRAS mutation statuses were characterized in 214 GCs in relation to their clinicopathological features and prognosis. The molecular subtypes based on CIMP and TP53 hot spot mutation status (R175, G245, R248, R273, and R282) best predicted prognosis of GC. These subtypes contained 120 CIMP‐positive (CIMP+) TP53 hot spot mutation‐negative (TP53 hot spot–) cases, 81 CIMP‐negative (CIMP–) TP53 hot spot– cases, 8 CIMP+TP53 hot spot mutation‐positive (TP53 hot spot+) cases, and 5 CIMP– TP53 hot spot+ cases. The CIMP–TP53 hot spot+ group presented the worst overall survival (OS) and progression‐free survival (PFS), followed by the CIMP+TP53 hot spot+, CIMP–TP53 hot spot– and CIMP+TP53 hot spot– groups (both P < 0.0001). These subtypes also correlated well with several aggressive clinicopathological features in that order. The molecular subtypes were independent factors for predicting overall survival (hazard ratio = 1.66, 95% CI = 1.07–2.57, P = 0.006). The molecular subtypes combining the CIMP and TP53 hot spot mutation status provide distinct clinicopathological features and prognostic impacts in GC. Association between molecular subtypes based on the CpG island methylator phenotype (CIMP), and TP53 hot spot mutation status and overall survival (OS) and progression‐free survival (PFS) in gastric cancer patients. [ABSTRACT FROM AUTHOR]

DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) infection is involved in a subset of gastric carcinoma (GC) cases, and is associated with distinct clinicopathological features. The present study reports a unique case of EBV-associated early-stage GC compared with the other cases experienced in our hospital. A 72-year-old male receiving treatment for cerebral infarction underwent an esophagogastroduodenoscopy (EGD) for suspicion of gastrointestinal bleeding. EGD revealed a type 0-I protruding lesion in the lesser curvature of the upper gastric corpus. Biopsy indicated well-differentiated adenocarcinoma. As the tumor diameter was >3 cm and the thickness of the tumor suggested submucosal invasion, laparoscopic gastrectomy was performed. Histological assessment revealed polypoid growth of an intramucosal, differentiated, tubular or papillary adenocarcinoma, with dense infiltration of lymphocytes. The carcinoma crypts were found to be EBV-positive on in situ hybridization. A review of the clinicopathological features of 25 EBV-associated GCs from 20 patients treated in our hospital between 2005 and 2014 was performed. All of these tumors, except that in the current case, appeared as shallow, depressed or ulcerative lesions. Thus, the current case appears to represent an unusual growth of EBV-positive GC. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (RIPK2), which encodes a component of the nucleotide binding oligomerization domain containing 2‑RIP2 pathway, may compromise the innate immune response to Helicobacter pylori infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between RIPK2 single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro‑duodenal endoscopy. Overall, the RIPK2 rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer [OR, 1.37; 95% confidence interval (CI), 1.06‑1.77; P=0.016], particularly of the intestinal type (OR, 1.53; 95% CI, 1.13‑2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI, 1.14‑2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild‑type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild‑type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type. [ABSTRACT FROM AUTHOR]

Background and Aim: Early‐stage gastric cancer (EGC) found after Helicobacter pylori (Hp) eradication often displays non‐tumorous regenerative epithelium and/or maturated tumorous epithelium overlying the cancerous tissue, which may confuse endoscopic and histological diagnosis. Probe‐based confocal laser endomicroscopy (pCLE) enables in vivo real‐time optical biopsy. We compared the diagnostic yields for these EGC cases using conventional white light endoscopy (WL), magnifying endoscopy with narrow‐band imaging (ME‐NBI), pCLE, and endoscopic biopsy; we also compared the accuracy of the horizontal extent diagnosis between ME‐NBI and pCLE. Methods: This study enrolled 30 patients with 36 EGC lesions after successful Hp eradication. Diagnostic yields of WL, ME‐NBI, pCLE, and endoscopic biopsy were prospectively compared. Four points of cancerous margins (oral, anal, anterior, and posterior sites) were also prospectively evaluated with M‐NBI and pCLE to determine the horizontal extent of the EGC. Results: Diagnostic yield was significantly higher with pCLE than with WL and endoscopic biopsy (97 vs 72%, 97 vs 72%, P = 0.0159, 0.0077, respectively), whereas it did not differ from ME‐NBI (88.9%, P = 0.371). Height of non‐tumorous regenerative epithelium or maturated atypical glands was 104.7 ± 34.2 μm in the pCLE‐positive cases, whereas it was 188.3 ± 27.1 μm in a pCLE‐negative case (P = 0.0004). Diagnostic accuracy of the horizontal margin of EGC was significantly higher with pCLE than with ME‐NBI (92 vs 70%, P = 0.0159). Conclusion: pCLE may be helpful for the diagnosis of ambiguous ECG found after Hp eradication because it enables real‐time scanning throughout the lesion and detection of subsurface microstructure. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy may improve outcomes in gastric cancer (GC), especially for the patients with advanced stage. To explore useful predictive factor for GC performing chemotherapy, we compared the tumor responses assessed using computed tomography (CT) with endoscopy based criteria. Methods: 192 GC patients performing chemotherapy were retrospectively studied. CT based response assessment was performed after 2 courses of treatment. Endoscopic evaluation according to The Japanese classification of gastric carcinoma was also performed at same period. Data were correlated with overall survival (OS) and progression-free survival (PFS). Results: Majority of the cases (n = 178, 93%) received S-1 based chemotherapy as the first line treatment. 55 (29%) and 91 (47%) cases were considered to be CT and endoscopic responders. Endoscopic responder was more clearly associated with better OS and PFS compared to CT based responder by the log-rank test (P<0.0001 vs. 0.01 and P<0.0001 vs. 0.008, respectively). The association was more striking among patients performing neoadjuvant chemotherapy (P<0.0001 vs. 0.15 and P<0.0001 vs. 0.1, respectively). Multivariate survival analysis using Cox's regression model revealed that endoscopic non-responder was the independent predictive factor, being more strongly associated with worse OS when compared to CT non-responder (hazard ratio: 4.60 vs. 1.77, 95% confidence interval: 2.83–7.49 vs.1.08–2.89, P<0.0001 vs. 0.02). More advanced T, N stage and cases who had peritoneal dissemination were significantly associated with endoscopic non-responder (all P values <0.01). Conclusion: Endoscopy based evaluation of primary lesions are clearly associated with prognosis in patients with GC who perform chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features. Methods: A total of 55 consecutive patients with 64 early gastric cancers (EGCs) diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored. Results: The majority of EGCs (63/64) were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001). The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05). The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers. Conclusions: Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

We investigated the methylation status of multidrug resistance 1 (MDR1) gene promoter in noncancerous gastric mucosa in relation to gastric cancer (GC) occurrence. Methylation of the MDR1 promoter was estimated in 127 GC and 82 non-GC patients. A significant association was found between higher methylation ratio and occurrence of GC. Higher methylation ratio was also associated with occurrence of GC in both Helicobacter pylori–positive and Helicobacter pylori–negative subjects. Higher MR was also associated with Helicobacter pylori infection. Methylation status of MDR1 gene in noncancerous gastric mucosa would be useful for predicting GC occurrence. [ABSTRACT FROM AUTHOR]

Background/Aim: We investigated the relationship of gastric cancer (GC) and CpG island hypermethylation (CIHM) in tumor suppressor genes of non-neoplastic gastric mucosa. Methods: Gastric mucosa samples were obtained from 125 GC and 180 non-GC subjects. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific polymerase chain reaction. High CIHM was defined as three or all methylated CpG islands. Results: Rates of CIHM of p14, CDH1, DAP-kinase, and high CIHM were significantly higher in all GC samples than non-GC samples (p14: 32.2 vs. 50.4%; OR = 1.70, 95% CI = 1.03–2.80, p = 0.04, CDH1: 36.1 vs. 84.0%; OR = 8.65, 95% CI = 14.74–15.77, p < 0.0001, DAP-kinase: 42.2 vs. 83.2%; OR = 5.98, 95% CI = 3.37–10.62, p < 0.0001, and high CIHM: 44.4 vs. 80.8%; OR = 4.40, 95% CI = 2.51–7.72, p < 0.0001). CIHM in CDH1 and DAP-kinase were associated with a greater risk of GC including all of its different subtypes. An increased number of CIHM was associated with an increased risk of all GC (1 CIHM; OR = 2.33, 95% CI = 0.82–6.64, p = 0.11, 2 CIHM; OR = 4.89, 95% CI = 1.79–13.37, p = 0.002, 3 CIHM; OR = 9.43, 95% CI = 3.20–27.78, p < 0.0001, and all CIHM OR = 24.71, 95% CI = 6.70–91.18, p < 0.0001). Three and all CIHM were closely associated with a higher risk of intestinal-type GC, Helicobacter pylori-positive infection status, male gender, and middle and older GC while 3 CIHM was closely associated with a higher risk of diffuse-type GC, H. pylori-negative infection status and younger GC. Conclusions: CIHM of CDH1 and DAP-kinase in non-neoplastic gastric mucosa corresponded to a risk of GC regardless of histological subtype, H. pylori infection status, gender and generation. An increased number of CIHM correlates with a higher GC risk including its various clinico-pathological subtypes. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Interleukin-17A (IL-17A) and IL-17F play a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We investigated the associations between gastric cancer and polymorphisms of IL-17A (rs2275913, G-197A) and -17F (rs763780, 7488 T/C) genes. The study was performed in 811 subjects (524 without gastric cancer and 287 with gastric cancer). We used the multiplex PCR-SSCP method to detect gene polymorphisms. Overall, the number of IL-17A/−197A allele was significantly correlated to the development of gastric cancer (OR, 1.42; 95% CI, 1.09–1.85; p = 0.010). The frequency of IL-17A/−197 A/A homozygote was also significantly higher in gastric cancer group than in non-cancer group (OR, 3.02; 95% CI, 1.86–4.91; p < 0.0001). The IL-17A/G-197A polymorphism was more closely correlated to intestinal-type cancer than diffuse-type cancer. In addition, IL-17A/−197A allele carriers had an increased risk of the development of gastric mucosal atrophy (OR, 1.68; 95% CI, 1.06–2.65; p = 0.026), and a positive relationship between the inflammation score and the number of −197A allele was observed (p = 0.022). We concluded that G-197A polymorphism of IL-17A gene was significantly associated with the development of gastric cancer, especially intestinal-type cancer. [Copyright &y& Elsevier]

Host genetic factors may play a key role in determining the long-term outcome of the Helicobacter pylori infection. Toll-like receptor 4 (TLR4) and CD14-mediated recognition of lipo-polysaccharide (LPS) is required for efficient recognition of gram-negative bacterial infections. We investigated the effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile, and CD14 promoter-C159T on the risk of gastric cancer including its subtypes and clinicopathologic features. We also investigated the effects of these polymorphisms on histologic degree of H. pylori-induced gastritis. The study was performed in 149 gastric cancer (GC) cases [mean age 64.0 +/- 12.4, M:F = 109:40] and 94 patients without evidence of GC (mean age 64.1 +/- 12.3, M:F = 65:25, Peptic ulcer diseases = 43.6%, gastritis = 56.4%) as the control group. TLR4 Asp299Gly, Thr399Ile, and CD14 promoter-C159T were determined by PCR-RFLP in all the patients. Gastritis scores of non-cancerous gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects (n = 179). The frequencies of CD14-260 TT and T carrier were significantly lower in patents with intestinal-type gastric cancer than in controls (OR = 0.31; 95%CI = 0.12-0.78, OR = 0.38; 95%CI = 0.18-0.81, respectively). Compared to patients older than 61 years, the atrophy score in antrum was significantly lower in TT and CT patients. TLR4 Asp299Gly and Thr399Ile were not detected in all the patients. Our data suggests that CD14 promoter-159TT and T carrier were associated with a lower risk of developing gastric mucosal atrophy in H. pylori-infected patients of more than 61 years of age, and these genotypes may reduce the risk of intestinal-type gastric cancer. [ABSTRACT FROM AUTHOR]

Objective. Superoxide has been implicated in the pathogenesis of Helicobacter pylori-related diseases through inflammation. NADPH oxidase, a major source of superoxide generation, plays a critical role in H. pylori-related gastric inflammation. The aim of this study was to clarify the effect of the p22PHOX C242T polymorphism, an essential component of NADPH oxidase in the risk of gastroduodenal diseases, on the severity of H. pylori-induced gastritis in a Japanese population. Material and methods. The study comprised 436 patients attending the Endoscopy Center of Fujita Health University Hospital. The p22PHOX C242T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system. Results. The 436 patients represented 106 gastric ulcers (24.3%), 48 duodenal ulcers (11.0%), and 282 non-ulcer subjects (64.7%). No association was found between p22PHOX polymorphism and the risk of ulcer diseases compared to non-ulcer subjects. However, among H. pylori-positive subjects, the degree of intestinal metaplasia tended to be lower in 242T carriers aged more than 60 years (p=0.0488). The same allele also decreased the risk of developing a more severe intestinal metaplasia in H. pylori-positive female subjects (p=0.0441). Conclusions. Our data suggest that the p22PHOX 242T allele is associated with a reduced risk of developing a more severe intestinal metaplasia in subjects older than 60 years of age and in female subjects with H. pylori infection. [ABSTRACT FROM AUTHOR]

Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 ( MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer. Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients. Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23–0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23–0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17–0.77), advanced cancer (OR = 0.31; 95% CI = 0.13–0.73), venous invasion (OR = 0.30; 95% CI = 0.10–0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13–0.65). Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population. [ABSTRACT FROM AUTHOR]

Background and Aim: Trypsin acting at protease-activated receptor 2 (PAR2) contributes to a progression of malignant tumors. An abnormal DNA methylation has been recognized as an important molecular mechanism for the genesis of various types of cancers. We attempted to clarify the relationship between the promoter methylation of PAR2 and gastric cancer. Method: We estimated the methylation of the PAR2 promoter in both antral non-cancerous mucosa and cancer lesions in 94 patients with gastric cancer. We employed a methylation-specific PCR method. Results: Regarding the methylation ratio (MR) of antral-non-cancerous mucosa, no significant difference was despite among gender, age and Helicobacter pylori infection status, whereas MR increased rising inflammation scores. The MR of cancer lesions was significantly lower than that of antral non-cancerous mucosa. This finding was not dependent on tumor staging, but also histological classification. In venous invasion, lymph node metastasis, or peritoneal dissemination negative cases, this significant lower MR was also seen. Conclusion: The promoter methylation of PAR2 seems to be increased with a progression of chronic inflammation and has an inhibitory effect on carcinogenesis of the stomach. [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29–91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]