p16基因甲基化与胃黏膜异型增生恶性转化的关系

目的 山东省临朐县是我国北方胃癌高发区之一,人群中胃黏膜异型增生(dysplasia,DYS)病变所占比例较高.DYS是胃黏膜癌前病变发展的高级阶段,具有显著的恶性转化潜能.本研究探讨p16基因甲基化与DYS病变恶性转化的关系,验证其作为胃癌预警标志物的应用价值.方法 以胃癌高发现场长期胃镜随访队列为基础,对101例来自山东省临朐县胃癌高发区且随访至2015-12-31的DYS病例,采用Methylight方法定量检测胃黏膜组织p16基因甲基化水平,评价其与DYS进展为胃癌风险的关系.结果 在进展为胃癌组,p16基因甲基化百分比中位数(四分位数)为1.30％(0.13％～1.87％),显著高于非进展组的0.67％(0～1.15％),P=0.047.与p16基因低甲基化者相比,高甲基化水平的DYS患者进展为胃癌的风险显著增加,OR-3.67,95％CI为1.31～10.34.进一步分析发现幽门螺杆菌(H.pylori)感染阳性者p16基因甲基化百分比中位数(0.98％)明显高于阴性者(0.01％),P＜0.001;分层分析发现,p16基因高甲基化同时H.pylori感染阳性者进展为胃癌的风险进一步增加,OR=5.14,95％CI为1.57～16.82.通过分析p16基因甲基化水平与DYS病例进展为胃癌的时间关系,发现随着胃癌诊断时间的临近,p16基因甲基化水平有缓慢升高的趋势,但差异未见统计学意义.结论 胃黏膜组织p16基因甲基化水平升高可作为DYS患者发生恶性转化的潜在预警标志物.     

Genetic polymorphism of PSCA and risk of advanced precancerous gastric lesions in a Chinese population

Objective: To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen (PSCA) and the risk of advanced precancerous gastric lesions including intestinal metaplasia(IM) and dysplasia(Dys), a population-based study was conducted in Linqu County, a high-risk area of gastric cancer (GC) in China.Methods: The prevalence of gastric lesions including superficial gastritis(SG), chronic atrophic gastritis(CAG), IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression.Results: Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM (OR=1.38, 95% CI=1.11-1.71) and Dys (OR=1.75, 95% CI=1.36-2.26), especially for subjects with H.pylori infection (IM: OR=1.34, 95% CI=1.05-1.71; Dys: OR=1.82, 95% CI=1.37-2.42). Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of 1M (OR=3.32, 95% CI=2.33-4.71) and Dys (OR=4.58, 95% CI=2.99-7.04).Conclusion: This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.     

Association between Gastric Pathology and Hepatitis B Virus Infection in Patients with or without Helicobacter Pylori

Background: In the recent years, hepatitis B virus (HBV) infection has been considered as a risk factor for gastriccancer, but further studies are required to confirm these claim. The present study was aimed to evaluate the correlationbetween gastric pathology (precancerous and cancerous conditions) with HBV infection in Helicobacter pylori (H. pylori)positive or negative patients. Methods: In this cross-sectional study, 728 patients under endoscopy examination in YazdShaheed Sadoughi Hospital between 2017 and 2018 were participated. Histopathological analysis was performed ongastric specimens. Hepatitis B surface antigen (HBsAg) in sera was detected by the enzyme-linked immunosorbent assay(ELISA). The relationship between gastric pathology and HBV infection were explored by logistic regression analysis.Results: Of 728 patients, HBsAg and H. pylori infection were detected in 83 and 408 patients, respectively. Sixty ninepatients were co-infected with H. pylori/HBV. H. pylori infection detected in patients with HbsAg positive significantlymore than those were negative for HbsAg (p=0.029). None of HBV/H. pylori co-infected patients did not have normalgastric tissue. A significant difference was seen in histopathology of gastric tissue between HBsAg positive patientswith and without H. pylori infection (p<0.0001). The HBsAg was associated with histopathology of gastric (OR=21.56,95℅CI=7.070-65.741, p<0.001) and as a risk factor for gastritis (OR=12.457, 95℅CI= 3.007-51.614, P=0.001) but nocancer (OR=2.127, 95℅CI=0.242-18.704, P=0.496). Conclusion: The HBV infection alone is associated with someprecancerous lesions but is not correlated with gastric cancer. It can increase development of premalignant conditionsand carcinoma significantly in H. pylori positive patients.     

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generationof aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotidepolymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastriccancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophyand 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqmanassay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Oddsratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Amonghealthy 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 significantcorrelation 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 ofH. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require furtherinvestigation.     

Determining Gastric Cancer-Related Risk Factors in Mongolian Population Using ABC(D) Method: A Matched Case-Control Study

Objective: We aimed to identify gastric cancer-related risk factors and evaluate the efficacy of screening ABC(D) method in determining high risk  gastric cancer individuals in Mongolian population. Methods: A total of 240 participants (120 gastric cancer patients and 120 healthy individuals) were included in this study. Data were collecting using a structured questionnaire consisting of 56 questions covering 5 categories. Serum Helicobacter pylori IgG (H. pylori IgG), pepsinogen I (PGI), and pepsinogen II (PGII) were tested in one third of all the participants (40 gastric cancer patients and 40 controls).  PGI, PGII, and H. pylori IgG levels were measured using GastroPanel enzyme-linked immunosorbent assay kit (Biohit, Helsinki, Finland). Results: Habits of having leftover meals (OR 2.22, 95%CI 1.27-3.86, p<0.01), daily consumption of tea with salt (OR 1.97, 95%CI 1.18-3.30, p<0.01), smoking on an empty stomach (OR 2.44, 95%CI 1.11-5.37, p<0.05), daily consumption of vegetables (OR 0.45, 95%CI 0.27-0.76, p<0.01), and daily consumption of fruit juice (OR 0.36, 95%CI 0.15-0.85, p<0.05), family history of gastric cancer (parents OR 2.88, 95%CI 1.07-7.78, p<0.05, siblings (OR 3.09, 95%CI 1.09-8.81, p<0.05), and history of gastric diseases (OR 3.65, 95%CI 2.10-6.35, p<0.0001) were identified as protective factors. A low PGI level (<35.25ng/ml) and low PGI/II ratio (<4) were associated with gastric cancer risk. According to ABC(D) method, groups C and D had higher proportion of gastric cancer cases than group A and B (group C, OR 7.50, 95%CI 1.20-47.05, p<0.05; group D, OR 8.3, 95%CI 1.33-51.26, p<0.05). Conclusion: Our findings suggested that gastric cancer risk was more closely related to eating habits, smoking, family history, and precancerous lesions. ABC(D) method seems to be a plausible alternative or supplementary method for stratifying patients at high risk of gastric cancer in this country.     

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.     

白介素10-1082G/A位点单核苷酸多态性与中国北方人群胃癌发病风险的病例对照研究

背景与目的:个体遗传易感性对胃癌的发生发展具有重要作用,其中免疫抑制因子白细胞介素10(interleukin-10,IL-10)基因-1082G/A位点单核苷酸多态性(single anucleotide polymorphism,SNP)引起研究者重视。本研究分析IL-10-1082G/A SNP在中国北方胃癌高发区和低发区人群中的分布,探讨IL-10-1082G/A SNP与胃癌发病风险的关系。方法:1516例研究对象来自胃癌高发区辽宁庄河(983例)及低发区沈阳(533例),采用聚合酶链反应-限制性片段长度多态(polymerase chain reaction-restriction fragment lengthpolymorphism,PCR-RFLP)方法检测该人群中IL-10-1082G/A位点单核苷酸多态性;采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测血清幽门螺杆菌(Helicobacter pylori,H.pylori)IgG。采用病理组织学诊断进行疾病分组,按性别和年龄配对,选取基本正常、浅表性胃炎、胃糜烂溃疡、萎缩性胃炎和胃癌组织各111例,用于IL-10-1082G/A SNP与胃癌发病风险的分析。结果:中国北方人群IL-10-1082G/A基因位点AA、AG、GG三种基因型分布频率分别为88.5%、10.9%、0.6%。IL-10-1082AG GG基因型在胃癌组、非胃癌组及正常对照组分布频率分别为19.8%、9.7%和6.3%,IL-10-1082AG GG基因型在胃癌高、低发区人群中的分布的地区及性别差异无统计学意义(P>0.05),而胃癌组高于非胃癌组(P=0.003)及正常对照组(P=0.003),其差异均有统计学意义。以IL-10-1082AA基因型并H.pylori IgG阴性的正常组为对照,IL-10-1082AG GG基因型并H.pylori IgG抗体阴性个体、IL-10-1082AA基因型或AG GG基因型并H.pylori IgG抗体阳性个体胃癌患病风险均提高,OR(95%CI)分别为3.3(1.3～8.6)、4.3(2.0～9.5)、2.5(2.1～3.1),但三组两两进行比较其差异均无统计学意义(P>0.05)。结论:携带IL-10-1082AG GG基因型个体胃癌的发病风险提高,IL-10-1082G/A SNP和H.pylori感染在胃癌发生发展过程中无交互作用。     

Determinants of gastric CDX2 expression: a study in Mozambique

As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in the intestinal differentiation pathway, study of these steps of gastric carcinogenesis may contribute toward understanding the early effects of gastric cancer determinants. Our aim was to quantify the association between Helicobacter pylori infection and other environmental factors and the gastric expression of CDX2. Dyspeptic patients undergoing an upper digestive endoscopy (Gastroenterology Department, Maputo Central Hospital) were consecutively invited to participate in this study and classified as having normal stomach/chronic nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG patients (sex-matched and age-matched, 1?:?2), H. pylori infection and CDX2 gene expression were assessed by histology and PCR and by immunohistochemistry, respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and all IM patients (n=12). It was more frequent among the H. pylori-infected patients (OR=2.26, 95% CI: 1.00-5.15). Infection with high-virulence strains was associated with CDX2 expression in patients with CAG (cagA, OR=3.20, 95% CI: 1.35-7.52) and IM (vacA m1, OR=5.86, 95% CI: 1.08-31.62). Patients with a lower frequency of vegetable consumption had a higher risk of marked CDX2 expression (OR=3.64, 95% CI: 1.02-12.95). The virulence of the infecting strains and vegetable consumption were associated with CDX2 expression and may play a role in the progression to more advanced lesions.     

Seroreactivity to Helicobacter pylori Antigens as a Risk Indicatorof Gastric Cancer

Background: Multiple etiologic factors are suspected to cause gastric cancer, the most important of whichis infection with virulent types of Helicobacter pylori. Materials and Methods: We have compared 102 gastriccancer patients with 122 non-ulcer, non-cancer dyspeptic patients. Gastric specimens were evaluated for H.pylori infection by tissue-based detection methods. Patient sera underwent antigen-specific ELISA and westernblotting using a Helicoblot 2.1 kit and antibody responses to various H. pylori antigens were assessed. Results:The absolute majority (97-100%) of both groups were H. pylori seropositive. Multivariate regression analysisdemonstrated serum antibodies to the low molecular weight 35kDa protein to be protective and reduce the riskof gastric cancer by 60% (OR:0.4; 95%CI:0.1-0.9). Conversely, seroreactivity to the 89kDa (VacA) protein wassignificantly higher in gastric cancer patients (OR:2.7; 95%CI:1.0-7.1). There was a highly significant association(p<0.001) between seroreactivity to the 116kDa (CagA) and 89kDa (VacA) proteins, and double positive subjectswere found at nearly five fold (OR:4.9; 95%CI:1.0-24.4) enhanced risk of gastric cancer as compared to doublenegative subjects. Conclusions: Seroreactivity to H. pylori low (35kDa) and high (116kDa/89kDa) molecularweight antigens were respectively revealed as protective and risk indicators for gastric cancer.     

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.     

The influence of promoter polymorphism of nuclear factor-erythroid 2-related factor 2 gene on the aberrant DNA methylation in gastric epithelium

Aberrant promoter methylation is an important mechanism for gene silencing. Inflammation-related reactive oxygens contribute to this CpG island methylation. The nuclear factor-erythroid 2-related factor 2 gene (Nrf2) is known to regulate the expression of detoxifying and antioxidant genes. We investigated the relationship between promoter polymorphisms of Nrf2 gene and the CpG island methylation in non-cancerous gastric mucosa. The study was performed in 85 subjects (46 without gastric malignancies, non-GC group, and 39 with gastric cancer, GC group). The promoter methylation status of p14(ARF), p16(INK4a) and p21(Waf1) genes was determined by methylation-specific-polymerase chain reaction. The Nrf2 gene genotypes were determined by the PCR-SSCP method. In the 85 subjects, CpG island methylation was found in 25.9% for p14, 15.3% for p16, none for p21. The frequency of the methylated genes was significantly higher in GC group than non-GC group (OR, 2.67; 95% CI, 1.10-6.49; p=0.029). In particular, the frequency of p16 gene methylation was much higher in GC group (p=0.0023). The Nrf2 -686/-684 G/G haplotype was positively associated and A/G haplotype was inversely associated with the development of CpG island methylation, especially p14 gene methylation (OR, 3.28; 95% CI, 1.26-8.59; p=0.015, and OR, 0.38; 95% CI, 0.15-0.96; p=0.040, respectively). In Helicobacter pylori (H. pylori) infected subjects, the number of -686/-684 G/G allele was positively correlated and that of A/G allele was inversely correlated to the methylation status, especially p14 methylation, by the adjusted analysis (OR, 2.90; 95% CI, 1.14-7.36; p=0.026, and OR, 0.33; 95% CI, 0.13-0.88; p=0.027, respectively). Our results suggested that the promoter polymorphisms of Nrf2 gene may affect the methylation status of tumor-related genes, especially the p14 gene, under the influence of H. pylori-induced gastric inflammation.     

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. Conclusions: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.     

Smoking, Helicobacter pylori virulence, and type of intestinal metaplasia in Portuguese males.

High-virulence Helicobacter pylori strains and smoking increase the risk of gastric precancerous lesions. However, its association with specific types of intestinal metaplasia has been poorly studied. We aimed to quantify the association between different types of intestinal metaplasia (complete, incomplete, and mixed) and these two risk factors. Male volunteers (n = 227) underwent an upper digestive endoscopy and completed symptoms and lifestyle questionnaires. A histologic diagnosis was assigned based on the lesions found in any of the biopsy specimens (antrum, body, or incisura). H. pylori vacA and cagA were directly genotyped by multiplex PCR and reverse hybridization. Each participant's smoking status at the time of endoscopy was assessed. Logistic and multinomial logistic regression models were fitted (including H. pylori virulence, smoking, age, and education as independent variables) using normal/chronic nonatrophic gastritis as the reference category. Compared with never smokers infected with low-virulence strains, the risk of intestinal metaplasia was increased in subjects infected with high-virulence strains [odds ratio (OR), 5.74; 95% confidence interval (95% CI), 1.68-19.63] and in ever smokers (OR, 3.54; 95% CI, 1.30-9.61). In ever smokers infected with high-virulence H. pylori strains, the risk of intestinal metaplasia was further increased (OR, 8.61; 95% CI, 3.07-24.17). Infection with high-virulence strains significantly increased the risk of incomplete (OR, 9.81; 95% CI, 2.39-40.31) and mixed (OR, 3.28; 95% CI, 1.51-7.14) intestinal metaplasia. Complete (OR, 2.82; 95% CI, 1.01-7.88) and mixed (OR, 2.97; 95% CI, 1.12-7.84) intestinal metaplasia were more frequent among ever smokers. High-virulence H. pylori strains and smoking are differentially associated with the complete and incomplete types of intestinal metaplasia, suggesting divergent pathways in gastric carcinogenesis.     

Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype.

BACKGROUND: In the general population, Helicobacter pylori (H. pylori), particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age < or = 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS: In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS: For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS: In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma.     

Helicobacter pylori Infection Impacts on Functional Dyspepsia in Thailand

Background: Helicobacter pylori (H. pylori) is a well known major cause of gastric cancer and even whenasymptomatic infected patients are at elevated risk. Functional dyspepsia (FD) is also one of the most commongastrointestinal diseases, which greatly impacts the quality of life. H. pylori infection and psychosocial stress arefrequently associated with FD but limited studies have confirmed the relationships, especially in Southeast Asiancountries. Here we aimed to investigate the prevalence and impact of H. pylori infection, anxiety and depressionon Thai FD patients. Materials and Methods: This cross-sectional study was conducted in a tertiary care centerin Thailand, during February 2013-January 2014. All FD patients were diagnosed and categorized by Rome IIIcriteria into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) groups. The HospitalAnxiety and Depression Scale was used to evaluate psychological status. The presence of H. pylori was definedas positive with H. pylori culture, positive rapid urease test or positive histology. Results: Three hundred FDpatients were included, 174 (58%) female. Overall mean age was 54.8+15.1 years. There were 192 (64%) patientswith PDS and 108 (36%) with EPS. H. pylori infection was demonstrated in 70 (23.3%) patients. Anxiety anddepression were documented in 69 (23%) and 22 (7.3%), respectively. H. pylori infection, anxiety and depressionwere significantly higher in PDS than EPS patients (27.1% vs 16.7%; p=0.04; OR=1.86; 95%CI=1.01-3.53 and29.7% vs 11.1%; p=0.0002; OR=3.4; 95%CI=1.7-7.1 and 10.4% vs 1.9%; p=0.006; OR=6.2; 95%CI=1.4-38.9,respectively). Conclusions: H. pylori infection, anxiety and depression were commonly found in Thai FD patientsand more prevalent in PDS than EPS. H. pylori eradication might be the key to success for the treatment of ThaiFD patients and prevent the development of gastric cancer.     

Does treatment of Helicobacter Pylori Infection Reduce Gastric Precancerous Lesions?

Background: Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, andmay inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determinethe effect of treatment on subsequent gastric precancerous lesion development. Materials and Methods: Weprospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasiaatrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy totreat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at followup two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greatercurvature, angularis, body of stomach and fundus. Results of these biopsies were compared before and aftertreatment. Results: Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotictherapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reductionof the atrophic lesions (p=0.01), but not metaplasia. Conclusions: Treatment of H. pylori likely is an effectivetherapy in preventing the development of subsequent gastric premalignant lesions.     

Association between C1019T polymorphism in the connexin 37 gene and Helicobacter pylori infection in patients with gastric cancer

Objective: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacterpylori infection in patients with gastric cancer. Methods: 388 patients with gastric cancer (GC), 204 with chronicsuperficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method.Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypesand alleles frequencies were compared. Results: (1) Connexin37 gene 1019 site distribution frequency (CC type,TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%,45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, thefrequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR = 2.01, 95%CI =1.58-2.57, P < 0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele(CC+TC) than in TT homozygote (OR = 2.47, 5%CI = 1.68- 3.610. (3) Gastric cancer patients complicated withHp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control groupmale patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and thefemale OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P <0.01). After eliminationof gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) Thedistribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative casesin the GC group (64.5% vs 47.0%, OR = 2.05, 95%CI = 1.54-2.74, P < 0.01). Compared with TT homozygotes,(CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR = 2.96, 5%CI = 1.76-2.99 ).Conclusion: The T allele in the connexin37 gene might not only be associated with gastric cancer but also withH. pylori infection.     

Salt Taste Preference,Sodium Intake and Gastric Cancer in China

Aim: The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pyloriand diet. By using a case-control study among residents in China, we examined the association between sodiumintake, presence of H,pylori, and gastric cancer risk. Methods: A population-based case-control study including235 cases and 410 controls were used. Potential risk factors of gastric cancer were interview for cases and controlsby questionnaire, salt taste preference was measured for all subjects, and IgG antibodies to H,pylori was usedfor H.pylori infection. Risk measures were calculated using unconditional logistic regression. Results: H.pyloriinfection and smoking increased the risk of gastric cancer, with the OR(95%CI) of 1.91(1.32-2.79) and 1.47(1.05-2.05), respectively. Dietary sodium intake independently increased the risk of gastric cancer. Participants withthe highest sodium intake(>5g/day) had a high gastric cancer risk [OR(95%CI)= 3.78(1.74-5.44)]. Participantswith the salt taste preference at 7.3g/L and ≥14.6g/L showed higher risk of gastric cancer [OR(95%) for 7.3g/Land ≥14.6g/L were 5.36(2.72-10.97) and 4.75(2.43-8.85), respectively]. A significantly interaction was foundbetween salt taste preference and H.pylori infection (p=0.037). Salt taste preference was significantly correlatedwith sodium intake (Correlation coefficient=0.46, p<0.001). Conclusion: Salt taste preference test could be asimple way to evaluate an inherited characteristic of sodium intake, and our study confirms the gastric canceris associated with sodium intake and H.pylori.     

Host-bacterial interaction in the development of gastric precancerous lesions in a high risk population for gastric cancer in Venezuela

Helicobacter pylori (HP) infection affects over 50% of the world's population. The prevalence is over 90% in populations at high risk for gastric cancer, but clinical outcomes of the infection are highly variable and thus host genetic factors have been suggested to play a role in its outcomes in addition to bacterial factors. In this study, we examined the effects of common functional genetic polymorphisms of several proinflammatory cytokines known to be overexpressed in HP-infected gastric mucosa on the risk of various stages of gastric premalignant lesions. The odds ratios (ORs) and 95% confidence intervals (CI) for atrophic gastritis, intestinal metaplasia and dysplasia were estimated by multinominal logistic regression analysis among 2,033 Venezuelan subjects. There was a significant effect of IL8 -251A allele on the prevalence of dysplasia (p = 0.021). The OR associated with the A-allele was 1.34 (95% CI: 0.82-2.18) for heterozygotes and 2.00 (95% CI: 1.13-3.56) for homozygotes, compared with the TT genotype. Furthermore, there was a statistically significant interaction between the number of A-alleles and HP cag A genotype (p = 0.009), suggesting that the A-allele increased the risk of dysplasia only when cag A was present. The OR for the AA compared with TT genotype was 3.22 (95% CI: 1.60-6.52) in this group. There were no associations with other proinflammatory cytokines studied, i.e., IL1 beta, IL6, monocyte chemoattractant protein 1 (MCP1) and TNF alpha, or with other stages of premalignant lesions. The present study provides important evidence suggesting host-bacterial interactions in the development of gastric precancerous lesions.