胃因性心律失常8例分析

笔者于1990～1994年遇到8例胃十二指肠球部病变活动时引起的心律失常误认为心因性心律失常现作回顾分析如下,供同道参考。 1 临床资料 本组中男6例,女2例,年龄20～55岁,病程15～60天,平均30天。 临床表现 规律性上腹部疼痛6例,上腹部饱胀7例,嗳气4例,反酸水5例,规律性心慌并活动后自觉症状消失8例,黑便2例。

胃因性心律失常8例分析

笔者于2000～2006年遇到8例胃十二指肠球部病变活动时引起的心律失常误认为心因性心律失常,现作回顾分析如下,供同道参考。

胃因性心律失常8例分析

胃因性心律失常８例分析江苏省丹阳卫校临床教研组姚桂香丹阳市人民医院邱锡定笔者于１９９０～１９９７年间遇到８例胃十二指肠球部病变活动时引起的心律失常，误诊为心因性心律失常，现作回顾分析如下：１临床资料本组中男性６例，女性２例，年龄２０～５５岁，病程１５...

Investigation of HER-2 codon 655 single nucleotide polymorphism frequency and c-ErbB-2 protein expression alterations in gastric cancer patients

AIM： To investigate both whether the risk of gastric cancer is associated with the Ile/Val single nucleotide polymorphism （SNP） of human epidermal growth factor receptor-2 （HER-2） transmembrane domain-coding region at codon 655 and the suggested existence of HER-2 expression in gastric cancer cases in a Turkish patient group. METHODS： Polymerase chain reaction （PCR） followed by restriction fragment length polymorphism （RFLP） strategy was used to analyze the presence of HER-2 SNP at codon 655. c-erbB-2 expression pattern was analyzed by immunohistochemistry. The results were compared between gastric carcinoma group and chronic gastritis group, as well as between clinicopathological parameters and carcinoma. RESULTS： Results showed that Ile/Val genotype accounted for 20% within the Turkish gastric carcinoma group, and none in chronic gastritis group, and this genotyping was associated with stage Ⅳ gastric cancers （P = 0.04）. Positive membranous HER-2 immunoreactivity, on the other hand, accounted for 24% within the Turkish gastric carcinoma group and none from chronic gastritis cases; further, it was correlated with intestinal type carcinomas （P = 0.007）, and stage Ⅲ-Ⅳ carcinomas （P = 0.004）. CONCLUSION： These observations imply that the tested HER-2 SNP may participate in the development and progression of gastric cancer. Thus, after confirming these results with large sample groups, HER-2 codon 655 SNP and/or c-erbB-2 overexpression may also be used as a poor prognostic indicator for gastric carcinomas.

Association betweenITGA2 C807T polymorphism and gastric cancer risk

AIM： To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer risk. METHODS： A hospital-based case-control study was conducted, including 307 gastric cancer patients and 307 age- and gender-matched control subjects. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS： The frequencies of the wild and variant genotypes in cases were significantly different from those of controls （P = 0.019）. Compared with individuals with the wild genotype CC, subjects with the variant genotypes （CT ＋ IT） had a significantly higher risk of gastric cancer （adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007）. In stratified analyses, the elevated gastric cancer risk was especially evident in older individuals aged 〉 58 years, nonsmokers and rural subjects. Further analyses revealed that the variant genotypes were associated with poor tumor differentiation and adjacent organ invasion in the sub-analysis of gastric cancer patients. CONCLUSION： The ITGA2 gene C807T polymorphism may be associated with an increased risk of gastric cancer, differentiation and invasion of gastric cancer.

XRCC1 genetic polymorphism Arg399Gln and gastric cancer risk:A meta-analysis

AIM： To evaluate the association between X-ray crosscomplementing gene 1 （XRCCl） genetic polymorphism Arg399Gln and gastric cancer risk by means of metaanalysis. METHODS： We searched PubMed and NCBI up to June 1, 2008. A total of 16 clinical trials and reports were identified, but only 8 trials qualified under our selection criteria. Statistical analysis was performed with the software program Review Manage, version 4.2.8. RESULTS： Of the 8 case-control studies selected for this meta-analysis, a total of 1334 gastric cancer cases and 2194 controls were included. For Arg399GIn, the Gin/Gin genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype （OR = 0.92, 95% CI, 0.71-1.19; P = 0.51）. Similarly, no associations were found in the recessive and dominant modeling （Gin/Gin vs Arg/GIn ＋ Arg/Arg： OR = 0.96; 95% CI, 0.77-1.19; P = 0.70 and Gin/Gin ＋ Arg/GIn vs Arg/Arg： OR = 0.90, 95% CI, 0.77-1.05; P = 0.18）. CONCLUSION： No association is found between the XRCC1 polymorphism Arg399GIn and gastric cancer risk.

Etiologic factors of gastric cardiac adenocarcinoma among men in Taiwan

AIM:To elucidate etiologic associations between Helicobacter pylori(H pylori),lifestyle,environmental factors and gastric cardiac adenocarcinoma(GCA)among men. METHODS:A hospital-based case-control study was conducted in Taiwan from 2000 to 2009.All cases were newly confirmed as primary GCA.Five controls were selected matching with age,sex,and admission date to each case.Participants were informedof potential risk factors with a structured question- naire by trained interviewers during hospitalization and provided a blood sample for the determination of H pylori infection.Odds ratio(OR)and 95%confidence interval(95%CI)were used to evaluate risk,and a multivariate conditional logistic regression model was performed. RESULTS:All participants recruited for this study were men,consisting of 41 cases and 205 controls.Results of the univariate analysis showed that significant factors associated with the etiology of GCA included H pylori(OR =2.69,95%CI=1.30-5.53),cigarette smoking(OR= 2.28,95%CI=1.05-4.96),working or exercising after meals(OR=3.26,95%CI=1.31-8.11),salted food (OR=2.51,95%CI=1.08-6.11),fresh vegetables(OR =0.28,95%CI=0.09-0.80),fruits(OR=0.19,95% CI=0.04-0.89),and rice as principal food(OR=0.53, 95%CI=0.30-0.85).Multivariate conditional logistic regression models indicated that a significantly elevated risk of contracting GCA was associated with working or exercising after meals(OR=3.18,95%CI=1.23-9.36) and H pylori infection(OR=2.93,95%CI=1.42-6.01). In contrast,the consumption of fresh vegetables(OR =0.22,95%CI=0.06-0.83),fruits(OR=0.28,95% CI=0.09-0.79)and rice as principal food(OR=0.48, 95%CI=0.24-0.93)remained as significant beneficial factor associated with GCA. CONCLUSION:Working or exercising after meals and H pylori infection increase the risk of GCA,but higher intakes of rice,fresh vegetables and fruits reduce the risk.

Cytochrome p450 2E1 polymorphisms and the risk of gastric cardia cancer

AIM: Genetic polymorphisms of drug-metabolizing enzymes have recently been shown to affect susceptibility to chemical carcinogenesis. Cytochrome P450 2E1 (CYP2E1) enzyme catalyzes the metabolism of many procarcinogens, such as N-nitrosamines and related compounds. The gene coding for this enzyme is polymorphic and thus may play a role in gastric cardia cancer (GCC) etiology. In this hospital-based case-control study, we evaluate the relationship between genetic polymorphisms of CYP2E1 and the risk of GCC. METHODS: The study subjects comprised 159 histologically confirmed GCC cases identified via hospital cancer registry and surgical records at five hospitals in Fuzhou, Fujian Province, China, between April and November 2001. Controls were 192 patients admitted to the same hospitals for nonmalignant conditions. The genotypes of CYP2E1 were detected by a PCR-based RFLP assay. The odds ratios were estimated by logistic regression analyses and were adjusted for potential confounding factors. RESULTS: The distribution of three genotypes of CYP2E1 in GCC cases and controls was significantly different (X2 = 16.04, P<0.01). The frequency of the CYP2E1 (c1/c1) genotype in GCC cases and controls was 60.4% and 40.1%, respectively. The CYP2E1 (c1/c1) genotype was associated with an increased risk for GCC (the adjusted (OR) was 2.37, 95% confidence interval (CI): 1.52-3.70). Subjects who carried the CYP2E1 (c1/c1) genotype and were habitual smokers were at a significantly higher risk of developing GCC (OR = 4.68,95%CT. 2.19-10.04) compared with those who had the CYP2E1 (c1/c2 or c2/c2) genotype and did not smoke. CONCLUSION: These results suggest that the CYP2E1 genotype may influence individual susceptibility to development of GCC, and that the risk increases significantly in smokers.

Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans

AIM： To observe the pharmacokinetics and pharmacodynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS： The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups： homozygous extensive metabolizers （homEM）, heterozygous extensive metabolizers （hetEM） and poor metabolizers （PM）. After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS： The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION： In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.

Helicobacter pylori infection in relation to E-cadherin gene promoter polymorphism and hypermethylation in sporadic gastric carcinomas

AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.METHODS: Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. Hpyloriwas detected by real-time PCR of the cagA gene from non-neoplastic epithelium.E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry.RESULTS: Hpyloriwas found in 57% of patients with GC.H pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs47%, P = 0.02). Hpylori infection was associated with E-cad methylation in nonneoplastic epithelium; however, no significant difference in H pylori was observed between methylated and unmethylated cancerous lesions.CONCLUSION: Patients with the -160C/C genotype might require Hpyloriinfection to promote the inactivation of CDH1, suggesting that Hpylori infection might affect GC in an initial stage because polymorphism is germ line.Mechanism of hypermethylation of CDH1 promoter in GC is complex, and Hpyloriinfection might affect it in an initial stage.

Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population

AIM： To examine the association of inducible nitric oxide synthase （iNOS） C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity.METHODS： A single nucleotide polymorphism of iNOS CtSOT was examined for 454 Japanese health checkup examinees （126 males and 328 females） aged 35 to 85 years without a history of cancer and 202 gastric cancer patients （134 males and 68 females） aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma.RESULTS： The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio （OR） of the C/T ＋T/T for gastric cancer was increased without statistical significance （OR=1.19, 95% confidence interval （CI）： 0.68-2.08）. In the differentiated subgroup （n = 113）, however, the OR of the C/T genotvpe for gastric cancer was significant （OR = 2.02, 95% CI： 1.04-3.92） relative to the C/C genotype. In addition, considering the location of gastric cancer （n = 105）, there were significant differences between the controls and non-cardia group with the ORof 2.13 （95% CI： 1.08-4.18） for C/T and 1.94 （95% CI： 1.00-3.78） for C/T ＋ T/T.CONCLUSION： The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancer in a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer

AIM： TO evaluate the association between poly- morphisms XRCC1 Arg194Trp and Arg399GIn and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS： Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis （CG） and 160 patients with gastric cancer （GC）, matched to 202 （Cl） and 150 （C2） controls, respectively. RESULTS： No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles （194Trp, 399Gin and 241Met） showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gin and XRCC3 241Met were related with gender, smoking, drinking and Hpylori infection in the CG and GC groups. CONCLUSION： Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilianpopulation, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities

AIM:To investigate the associations between interleukin(IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet,Hui and Han ethnicities.METHODS:Genomic DNA was extracted from peripheral blood of 210,205,and 202 healthy volunteers and from 155,158,and 197 gastric cancer patients from the Tibet,Hui,and Han populations,respectively.Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography.RESULTS:Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio(OR) = 2.17,P = 0.037] in the Tibet ethnicity.Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer(OR = 2.08,2.31,P = 0.007,0.016,respectively) in the Hui ethnicity.In the Han population,carriers of the IL-1B-31 CC,IL-1B-511CT,TT genotypes had increased risk of intestinal type gastric cancer(OR = 2.51,2.74,5.66,P = 0.005,0.002,0.000,respectively).CONCLUSION:IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet,Hui,and Han ethnicities in the Qinghai area of China.

Risk for gastric neoplasias in patients with chronic atrophic gastritis:A critical reappraisal

Chronic atrophic gastritis （CAG） is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue （non-metaplastic atrophy） or by glandular structures inappropriate for location （metaplastic atrophy）. Epidemiological data suggest that CAG is associated with two different types of tumors： Intestinal-type gastric cancer （GC） and type I gastric carcinoid （T I GC）. The pathophysiological mechanisms which lead to the development of these gastric tumors are different, It is accepted that a multistep process initiating from Helico- bacterpylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The T I GC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of T I GC. Thus, several events occur in the gastric mucosa before the development of intestinatype GC and/ or T I GC and these take several years. Knowledge ofCAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors as- sociated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

Genetic alterations in benign lesions:Chronic gastritis and gastric ulcer

AIM： To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TPS3 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. METHODS： Gastric biopsies from normal mucosa （NM, n = 10）, chronic gastritis （CG, n = 38）, atrophic gastritis （CAG, n=13） and gastric ulcer （GU, n=21） were studied using fluorescence in situ hybridization （FISH） and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect Hpylori. An association of the gastric pathologies and aneuploidies with Hpylori infection was assessed. RESULTS： Aneuploidies were increasingly found from CG （21%） to CAG （31%） and to GU （62%）, involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG （P=0.0143） and GU （P=0.0498）. No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% （5/11） and 12% （2/17） of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. CONCLUSION： The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with Hpylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa.

Association of the myeloperoxidase ^(468)G→K polymorphism with gastric inflammation and duodenal ulcer risk

AIM: To elucidate the relations between the myeloperoxidase ^(-468)G→a polymorphism and the development of duodenal ulcer (DU), and to investigate the impacts of this host genetic polymorphism on the histopathological features of Helicobacter pylori (H py/ori)-related gastritis. METHODS: In a case-control study of 115 consecutive DU patients and 182 controls, the myeloperoxidase ^(-468)G→A polymorphism was genotyped. Additionally, gastric mucosal changes were examined according to the updated Sydney System. RESULTS: The two study groups differed in the distributions of myeloperoxidase genotypes (P=0.008). All six individuals carrying myeloperoxidase A/A genotypes were in the DU group. The carriage of myeloperoxidase allele A and H pylori infection were associated with an increased risk of DU with odds ratios (OR) of 2.3 and 5.8, respectively. The combined risk of the carriage of myeloperoxidase allele A and H pylori infection for DU was 8.7 (95% CI, 3.5-21.8). In the H pylori-infected individuals, allele A carriers displayed higher bacterial density scores (P=0.04) in the antrum than did non-carriers. CONCLUSION: This work verifies for the first time the association of myeloperoxidase ^(-468)G→A polymorphism with antral H pylori density and DU disease. The mechanisms underlying this genetic polymorphism in developing DU disease merit further investigations.

Interaction models of CYP1A1, GSTMl polymorphisms and tobacco smoking in intestinal gastric cancer

AIM： To explore the interaction models of the cytochrome P-450 （CYP） 1A1 Valvariant and glutathione S-transferase （GST） M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS： A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblingsin-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS： The frequency of the CYPIA1 Valvariant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 （95% confidence interval [95%CI]： 1.2-3.1, P〈0.01）. It showed a significant type 2 form of interaction model when both CYPIA1 Valvariant allele and former tobacco smoking existed （i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYPIA1 variant alone）. The interaction index y was 2.8, and OReg （95%CI） was 5.0 （1.9-13.4）. GSTM1 null genctype and former tobacco smoking were significant in a type 4 interaction model （i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects）. The interaction index y and OReg （95%CI） were 3.4 and 8.4 （3.4-20.9）, respectively.CONCLUSION： Different interaction models of CYPIA1 Valvariant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.

Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients

AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUSA） method. RESULTS： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （OR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, OR = 13.07; 95% CI, 2.82-85.14）.CONCLUSION： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.