The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea

Background/Aims

The potential role of the cyclooxygenase (COX)-2 polymorphism has been reported in relation to the risk of gastrointestinal tract malignancies. Therefore, we investigated whether COX-2 polymorphisms are associated with the risk of gastric cancer (GC) in Korea, one of the areas with a high prevalence of this condition.

Methods

We evaluated the genotypic frequencies of COX-2-765 and -1195 in 100 peptic ulcer patients, 100 GC patients, and 100 healthy controls. The polymorphisms of the COX-2-765 and -1195 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphisms.

Results

The frequencies of the COX-2-1195 GG, GA, and AA genotype were 20%, 60%, and 20% in intestinal-type GC and 8%, 48%, and 44% in diffuse-type GC, respectively (p=0.021). There were no significant differences in the frequency of COX-2-765 genotypes between intestinal-type GC and diffuse-type GC (p=0.603). Age- and sex-adjusted logistic regression analysis showed that the COX-2-1195 AA genotype was the independent risk factor of diffuse-type GC compared with the COX-2-1195 GG genotype (p=0.041; odds ratio, 6.22; 95% confidence interval, 1.077 to 35.870).

Conclusions

The COX-2-1195 AA genotype may render subjects more susceptible to diffuse-type GC.     

环氧化酶-2基因启动子区多态性与结直肠癌的易感性

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)基因启动子区的-1195(G/A,rs689466)及3’非翻译区的8473(T/C,rs5275)2个位点的基因多态性与结直肠癌(colorectal cancer,CRC)发病风险的相关性.方法:采用病例-对照研究,利用聚合酶链式反应和限制性片段长度多态性(polymerase chain reaction-restrictive fragment length polymorphism,PCR-RFLP)分析方法,对343例CRC患者和340例健康人的COX-2基因的2个位点的多态性进行检测,采用SPSS11.0软件包统计分析各位点的基因型分布和等位基因频率.结果:COX-2-8473位点多态性的各基因型频率在病例组及对照组中分布均无显著差异(P>0.05),但COX-2-1195位点多态性的基因型频率在二组中分布有显著性差异(P<0.001),结果显示CRC患者COX-2-1195AG基因型在病例组的频率较对照组显著增高(校正后OR=2.23;95%CI:1.50-3.32),AA基因型在病例组中的频率亦较对照组高(校正后OR=2.46;95%CI:1.51-4.02),A等位基因携带者在病例组中的频率高于对照组(校正后OR=2.27;95%CI:1.55-3.34).各基因型分布在结肠癌及直肠癌中的分布无显著性差异(P>0.05).COX-2-1195A等位基因与淋巴结转移及TNM分期有显著相关性.结论:COX-2-1195位点AG/AA基因型是CRC的风险因素,且与CRC的淋巴结转移及TNM分期相关.     

Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: a meta-analysis

AIM: To investigate the association of the cyclooxygenases-2 (COX-2) polymorphisms and susceptibility to gastric cancer (GC) by means of meta-analysis. METHODS: Publications addressing the association between polymorphisms of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and CBMdisc databases. Data was extracted from the studies by 2 independent reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data, odds ratio (OR) with 95% confidence interval (CI) was calculated.RESULTS: Ten studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of -765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P = 0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P = 0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively). CONCLUSION: The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.     

环氧合酶-2基因启动子区单核苷酸多态性与非酒精性脂肪肝遗传易感性的关系

目的 通过检测环氧合酶-2(COX-2)基因启动子区单核苷酸的多态性,以探讨其与非酒精性脂肪肝(NAFLD)遗传易感性的关系.方法 对200例NAFLD患者和206名正常对照,采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法对COX-2基因启动子区-765G＞C和-1195G＞A多态性进行基因型分析.计量资料结果用均数±标准差((-x)±s)表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行x2检验.结果 正常对照中,COX-2基因启动子区-765G＞C和-1195G＞A等位基因的分布频率分别为48%和2%,NAFLD患者组二者分别为54%和5%.多变量Logistic回归分析显示:-765GC基因携带者与-765GG基因携带者相比较,前者发生NAFLD的比值比(OR)=2.35 (95% CI为1.17～3.65);-1195AA基因携带者与-1195GG基因携带者相比较,前者发生NAFLD的OR=1.13 (95% CI为1.01～2.46).与单体型G-1195-G765相比较,含有A1195的A-1195-C-765、A1195-G765两种单体型发生NAFLD的相对风险明显升高,OR分别为1.42 (95% CI为1.11～1.63,P＜0.05)和4.24(95% CI为1.72～14.22,P＜0.01).且A-1195-C765发生NAFLD的OR值高于A-1195-G-765、G-1195-C765的单体型.这一结果提示在同一单体型内-1195A与-765C之间存在交互作用.结论 COX-2基因启动子区的-1195G＞A和-765G＞C单核苷酸存在多态性,与NAFLD发生相关,是决定NAFLD个体遗传易感性的重要因素.     

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in Cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.     

Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer

BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, -1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and 2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(-1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G-->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer.     

COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因,探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点,以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异,-511CT／-31CT（OR=2．256,95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312,95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033）,GG基因型胃癌发病风险显著高于CG基因型（OR=2．796,95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险,TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。     

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

AIM: To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.METHODS: We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylori (H. pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H. pylori infection. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, including sex and age as confounding factors.RESULTS: The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer (OR 0.50, 95% CI: 0.26-0.95, P = 0.04) while the rs7789045 TT genotype showed an increased risk (OR 2.14, 95% CI: 1.20-3.82, P = 0.01). An elevated susceptibility to gastric cancer was observed in the subjects with H. pylori infection and the NaOD1 rs7789045 TT genotype (OR 2.05, 95% CI: 1.07-3.94, P = 0.03) or the NOD2 rs7205423 GC genotype (OR 2.52, 95% CI: 1.05-6.04, P = 0.04). Haplotype analysis suggested that the distribution of AGT (rs2907749, rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different (P corrected: 0.04), and the diplotype AGT/AGT was associated with an elevated gastric cancer risk (OR 1.98, 95% CI: 1.04-3.79, P = 0.04). The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H. pylori-related diffuse-type gastric cancer (OR 3.00, 95% CI: 1.38-6.53, P = 0.01; OR 4.02, 95% CI: 1.61-10.05, P < 0.01, respectively).CONCLUSION: Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.     

Association of Helicobacter pylori infection with atrophic gastritis and intestinal metaplasia

AIMS: To evaluate the effect of Helicobacter pylori infection and aging on atrophy and intestinal metaplasia of the gastric mucosa. METHODS: One hundred and sixty-three patients were divided into three age groups and underwent an upper gastrointestinal endoscopy where no esophagitis, peptic ulcers, or malignancies were detected. Two biopsy specimens were obtained from the anterior and posterior walls of the antrum and of the fundus. These were used to evaluate the grade of gastritis, bacterial culture and histologic evidence of H. pylori infection. RESULTS: Helicobacter pylori infection was found to be directly associated with an increased risk of gastritis grade (odds ratio (OR) = 90 (95% CI; 30-270)). An age of 60 years and older along with H. pylori infection was also strongly associated with an increased risk of atrophy (OR = 6.6, (95% CI; 2.9-15.2)); OR = 9.8, (95% CI; 2.7-35.4)), as was intestinal metaplasia of the gastric mucosa (OR = 5.5, (95% CI; 1.7-17.6)); OR = 7.9, (95% CI; 2.8-46.1)). The prevalence of atrophic gastritis increased with advancing age in H. pylori-infected patients, but no such phenomenon was observed in H. pylori-uninfected patients. The prevalence of intestinal metaplasia significantly increased with advancing age, irrespective of the presence of H. pylori infection. In addition, H. pylori uninfected female patients had a decreased risk of intestinal metaplasia. CONCLUSIONS: These results suggest that atrophic gastritis is not a normal aging process, but instead is likely to be the result of H. pylori infection, while intestinal metaplasia is caused by both the aging process and H. pylori infection. A decreased risk of intestinal metaplasia found in uninfected female subjects may partly explain the lower prevalence of gastric cancer in females than in males.     

Complete and incomplete intestinal metaplasia at the oesophagogastric junction: prevalences and associations with endoscopic erosive oesophagitis and gastritis

BACKGROUND/AIMS: Intestinal metaplasia (IM) is a common finding at the oesophagogastric junction, but the aetiopathogenesis of the different IM subtypes-that is, incomplete IM (specialised columnar epithelium, SCE) and complete IM- and their associations with gastro-oesophageal reflux disease and Helicobacter pylori gastritis are unclear. METHODS: 1058 consecutive dyspeptic patients undergoing gastroscopy were enrolled. The gastric, oesophagogastric junctional, and oesophageal biopsy specimens obtained were stained with haematoxylin and eosin, alcian blue (pH 2.5)-periodic acid Schiff, and modified Giemsa. RESULTS: Complete junctional IM was detected in 196 (19%) of the 1058 subjects, and in 134 (13%) was the sole IM subtype. Incomplete junctional IM (SCE) was detected in 101 (10%) subjects, of whom 62 (61%) also had the complete IM subtype. Of patients with normal gastric histology (n = 426), 6% had complete IM and 7% junctional SCE. The prevalence of both types of IM increased with age in patients with either normal gastric histology or chronic gastritis (n = 611). Epithelial dysplasia was not detected in any patients with junctional IM. In multivariate analysis, independent risk factors for incomplete junctional IM were age (odds ratio (OR) 1.3 per decade, 95% confidence interval (CI) 1.2 to 1.6), endoscopic erosive oesophagitis (OR 1.9, 95% CI 1.1 to 3.2), and chronic cardia inflammation (OR 2.9, 95% CI 1.3 to 6.2), but not gastric H pylori infection (OR 1.0, 95% CI 0.6 to 1.7). In univariate analysis, junctional incomplete IM was not associated with cardia H pylori infection. Independent risk factors for "pure" complete junctional IM (n = 134) were age (OR 1.2 per decade, 95% CI 1.0 to 1.4), antral predominant non-atrophic gastritis (OR 2.6, 95% CI 1.3 to 5.2), antral predominant atrophic gastritis (OR 2.1, 95% CI 1.1 to 5.2), and multifocal atrophic gastritis (OR 7.1, 95% CI 2.5 to 19.8). In univariate analysis, junctional complete IM was strongly associated with chronic cardia inflammation and cardia H pylori infection (p<0. 001). CONCLUSIONS: Both complete and incomplete junctional IM are independent acquired lesions that increase in prevalence with age. Although IM subtypes often occur simultaneously, they show remarkable differences in their associations with gastritis and erosive oesophagitis: junctional complete IM is a manifestation of multifocal atrophic gastritis, while the incomplete form (SCE) may result from carditis and gastro-oesophageal reflux disease. The frequency of dysplasia in intestinal metaplasia at the oesophagogastric junction appears to be low.     

Polymorphism of -765G 〉 C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection：A study from northern India

AIM： To investigate -765G 〉 C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease （PUD） and nonulcer dyspepsia （NUD）. METHODS： We enrolled 348 adult patients （62 gastric adenocarcinoma, 45 PUD and 241 NUD） undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests （RUT, culture, histopathology and PCR） were positive. Genotyping for -765G 〉 C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS： Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P 〈 0.001, odds ratio （OR） 8.20; 95% confidence interval （95% CI）, 4.08-16.47] and PUD （77.4% vs 31.1%, P 〈 0.001; OR 8.04; 95% CI, 3.25-19.90）. Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with （OR 7.83; 95% CI 3.09-19.85） and without H pylori infection （OR 7.06; 95% CI, 2.61-19.09）. Patients with C carrier and H pylori infection had significant risk for the development of PUD （P 〈 0.001; OR 5.65; 95% CI, 2.07-15.34）. CONCLUSION： -765G 〉 C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.     

A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma

BACKGROUND & AIMS: Pro-inflammatory polymorphisms within the genes interleukin (IL)-1B and IL-1RN are associated with risk for gastric carcinoma (GC) in Helicobacter pylori-infected individuals. We aimed to determine the association between variation of the tumor necrosis factor (TNF)-alpha gene and the risk for chronic atrophic gastritis (CAG) and GC. We also investigated the extent to which the combined effect of proinflammatory genetic polymorphisms (IL-1B, IL-1RN, and TNF-alpha), and the combined effect of TNF-alpha and bacterial genotypes each influence such a risk. METHODS: In a case-control study including 306 controls, 221 individuals with chronic gastritis, and 287 GC patients, the TNF-alpha-308 and IL-1B-511 bi-allelic polymorphisms, the IL-1RN variable number of tandem repeats (VNTR), and the H. pylori genes vacA (s and m regions) and cagA were genotyped. RESULTS: We found that carriers of the TNF-alpha-308*A allele are at increased risk for GC development with an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.3-2.7). For both CAG and GC, the odds of developing disease increased with the number of high-risk genotypes. Individuals carrying high-risk genotypes at the 3 loci are at increased risk for CAG and GC with an OR of 5.8 (95% CI, 1.1-31.0) and 9.7 (95% CI, 2.6-36.0), respectively. The risk for GC was not affected significantly by the combination of bacterial and TNF-alpha-308 genotypes. CONCLUSIONS: These findings show that a proinflammatory polymorphism in the TNF-alpha gene is associated with increased risk for GC, and that it is possible to define a specific genetic profile associated with highest risk for CAG and GC.     

Association between COX-2-1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

AIM To perform a meta-analysis to investigate the association between cyclooxygenase-2(COX-2)-1195GA gene polymorphism and gastrointestinal cancers. METHODS Publications related to the COX-2-1195GA gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from Pub Med, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios(ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg's rank correlation test, and Egger's linear regression method were applied to analyse whether the included publications had publication bias. RESULTS A total of 24 publications related to the COX-2-1195GA gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2-1195GA gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer(A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2-1195GA gene polymorphism in the Asian population(A vs G: OR = 1.30; AA/AG vs GG: OR= 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis(P 0.05) and the false positive report probability(P 0.2) confirmed the reliability of the results. CONCLUSION The results showed that the COX-2-1195GA gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.     

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

~~Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients@Roberto Herrera-Goepfert$Department of Pathology, Institute Nacional de Cancerologia (INCan), Mexico City, Mexico @Jesús K Yamamoto-Furusho$Dep…     

环氧化酶2基因多态性与急性冠状动脉综合征的关联研究

目的探讨环氧化酶2(COX-2)基因-1195G>A和-765G>C位点与中国汉族人群急性冠状动脉综合征(ACS)的相关性。方法选择ACS患者250例(ACS组),同期选取健康体检者266例(对照组)。采用扩增阻碍突变系统结合TaqMan探针的实时荧光定量PCR方法对COX-2基因多态性位点(-1195G>A和-765G>C)进行基因分型。多因素logistic回归分析各多态性位点与ACS的相关性。结果在男性中,ACS组-1195G>A基因型及等位基因频率与对照组比较,差异有统计学意义(GG:23.4%vs 33.8%,GA:50.6%vs 49.4%,AA:25.5%vs 16.9%,P=0.049;G:48.7%vs 58.4%,A:51.3%vs 41.6%,P=0.014);与-1195G>A位点GG基因型比较,AA+GA基因型发生ACS的风险更高(P=0.042),行多因素分析校正相关危险因素后,差异有统计学意义(OR=1.971,95%CI:1.130³.438,P=0.017)。在女性中,ACS组-1195G>A位点基因型及等位基因频率与对照组比较,差异无统计学意义(P>0.05)。单体型分析提示,在男性中,ACS组A-1195-765-G频率显著高于对照组,差异有统计学意义(P=0.012),而在女性中,ACS组A-1195-765-G频率差异无统计学意义(P>0.05)。结论在中国汉族人群中,COX-2基因-1195G>A基因多态性以及单体型A-1195-765-G与男性ACS有关,与女性无关。     

Helicobacter pylori infection and low serum pepsinogen I level as risk factors for gastric carcinoma

AIM: To study whether examination of CagA antibodies could increase the odds ratio for gastric cancer in a casecontrol study, and how often other serum markers of gastric cancer risk could be found in Helicobacter pylori-negative patients. METHODS: H pylori CagA and parietal cell antibodies (PCAs), and serum pepsinogen I (SPGI) levels were compared between patients with gastric cancer and controls who received endoscopic examination due to reasons other than gastrointestinal malignancy. RESULTS: The odds ratio (OR) for gastric cancer was 2.9 (95% CI 1.4-5.8) in H pylori + patients, and 2.4 (95% CI 1.2-4.9) in CagA+ patients. When results of H pylori and CagA antibodies were combined, OR increased to 5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were excluded, the OR increased to 6.8 (95% CI 3.1-14.8). Among patients with a low SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant only in the older age group. The number of patients with low SPGI was significantly higher in H pylori -/CagA+ patients as compared to other cancer patients. CONCLUSION: Examination of both H pylori and CagA antibodies increases the OR for gastric cancer in our casecontrol study. CagA antibodies are important in detecting previous H pylori infection in advanced atrophic gastritis or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be helpful in screening elderly gastric cancer patients.     

Endoscopic Patterns and Histopathological Features after Eradication Therapy in <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-Associated Nodular Gastritis

The endoscopic finding of nodular gastritis (NG) is highly associated with presence of Helicobacter pylori infection. How the endoscopic patterns and histopathology of NG change after eradication of H. pylori is unclear. Twenty-one adults (3 men and 18 women) with H. pylori-associated NG found on endoscopy were enrolled for this study. The histological findings included gastritis activity, bacterial colonization, and lymphoid follicles. Repeat endoscopy for the endoscopic as well as histopathological features of gastric biopsy specimens was performed 2 months later after eradication treatment. H. pylori was successfully eradicated in 19 patients. Endoscopic NG disappeared in 12, improved in 5, and was unchanged in 4. After treatment, there was significant improvement in scores for gastritis activity [P < 0.001, 95% confidence interval (CI) 1.31-1.91], bacterial colonization (P < 0.001, 95% CI 0.71-1.14) and follicular gastritis (P = 0.047, 95% CI 0.04-0.52), primarily among patients whose endoscopic pattern resolved completely. The disappearance of nodularity on endoscopy was accompanied by a decrease in follicular gastritis score.     

Helicobacter pylori Infection and Gastric Neoplasia: Correlations With Histological Gastritis and Tumor Histology

Objective: Several authors have reported an association between Helicobacter pylori ( H. pylori ) and gastric carcinoma, but the data are conflicting. Atrophic gastritis and intestinal metaplasia (IM) have also been linked to gastric carcinoma, especially the intestinal tumor type. We investigated the relationship between H. pylori infection, gastric neoplasms, and histological gastritis.
Methods: A total of 105 patients with gastric carcinoma, 36 patients with gastric adenoma, and 105 age- and sex-matched control subjects were examined for H. pylori infection and histological gastritis. H. pylori status was evaluated by Giemsa staining and IgG serology. Mucosal inflammation, atrophy, and IM were evaluated in biopsy specimens from antrum and corpus.
Results: H. pylori seroprevalence was higher in patients with gastric carcinoma (98 of 105, 93%) and adenoma (34 of 36, 94%) than in control subjects (82 of 105, 71%,   p < 0.05  ). H. pylori was more prevalent in patients with noncardia (OR, 5.67; 95% CI, 2.25–14.44) than cardia (OR, 5.20; 95% CI, 0.65–41.68) tumors. Histologic types and tumor stage (early; OR, 6.60; 95% CI, 2.23–19.69, advanced; OR, 4.27; 95% CI, 1.21–15.03) showed no difference in H. pylori prevalence. Atrophy and IM scores were higher in patients with the intestinal- but not diffuse-type of carcinoma and adenoma than in H. pylori -positive control subjects. Smoking was associated with gastric carcinoma (OR, 3.05; 95% CI, 1.58–5.93) but not alcohol or coffee use, blood group A, or a family history of gastric cancer.
Conclusions: Our results confirm a strong association between H. pylori and gastric carcinoma and adenoma. The intestinal-type gastric carcinoma is associated with atrophic gastritis and IM.