Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection

BACKGROUND: Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori-induced gastric atrophy. METHODS: Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti-H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. RESULTS: The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26-6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01-4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39-0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori-seropositive and -seronegative groups. In the H. pylori-seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12-6.93) had a significant association with gastric atrophy. CONCLUSIONS: These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer.     

Helicobacter pylori and Gastroesophageal Reflux Disease: A Case–Control Study

Background:  Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict.
Methods:  We conducted a case–control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein.
Results:  Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15–0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08–0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09–0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori -positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms.
Conclusions:  H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.     

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.     

Association of Helicobacter pylori-related distal gastric cancer with the HLA class II gene DQB10602 and cagA strains in a southern European population

BACKGROUND: Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population. MATERIAL AND METHODS: In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies. RESULTS: Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the (*)0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1(*)0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94). CONCLUSION: Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.     

Genetic susceptibility and risk of gastric cancer in a human population of Cauca, Colombia

Gastric cancer (GC) is the main cause of mortality by cancer in Colombia. Glutathione S-transferase (GST) enzymes are involved in the detoxification of many environmental carcinogens. The homozygous deletions of glutathione S-transferase M1 (GSTM1-0) and glutathione S-transferase T1 (GSTT1-0) have been associated with several types of cancer. The risk to develop GC has been associated with environmental factors and Helicobacter pylori infection. The tumor necrosis factor (TNF-alpha) and its levels are increased in patients infected with H. pylori. A G/ A transition in the position -308 of the promoter of the TNF-alpha has been related in several studies to an increased expression of the gene and is associated with susceptibility to GC. The association of these polymorphisms with GC and the interaction with other risk factors (life style) were investigated. Blood samples were obtained from 46 GC patients and 96 controls. The logistic regression model was used to obtain the odds ratio (OR) and their 95% confidence intervals. These statistics established the association between the enzymatic polymorphisms and GC and between other independent factors and GC. The frequency of the TNF-alpha polymorphism in people infected with H. pylori was 18% in the GC population and 7% in the control group. This transition was not significantly associated with H. pylori infection and GC. The frequencies of the deletion polymorphisms for patients and controls were as follows: GSTM1 65.2% and 37.5%; GSTT1 17.4% and 14.6%. These results suggested that the GSTM1 deletion polymorphism was associated with an increased risk of gastric cancer (OR of 5.5; 95%CI, 1.7-17.2). Furthermore, other risk factors such as H. pylori infection (OR 5.58, CI 1.8-17.2), smoking (OR 6.70, CI 2.2-20.3) and alcohol intake (OR 3.27, CI 1.1-9.4) were associated with GC.     

Clinical relevance of the cagA,vacA and iceA genotypes of Helicobacter pylori in Brazilian clinical isolates

Infection with Helicobacter pylori strains harboring determinants of pathogenicity may lead to a strong inflammatory response in gastric mucosa. In this work, we examined the frequency of the cagA, vacA and iceA genotypes in H. pylori strains isolated from Brazilian patients and correlated these with the clinical manifestations. H. pylori was isolated from 165 patients [30 with non-ulcer dyspepsia cases (NUD); 93 peptic ulcer disease (PUD): 31 gastric ulcers (GU) and 62 duodenal ulcer disease (DU); 18 with erosive gastritis (EG); and 24 gastroesophageal reflux disease (GERD)]. Allelic variants of cagA, vacA and iceA were identified using the polymerase chain reaction. More than one H. pylori strain was detected in 28 cases (17%), and these were excluded from the statistical analysis. We were unable to confirm an association between iceA status and clinical outcome. There was a strong association between the genotype cagA-positive vacA s1 and PUD. However, logistic regression analysis showed that vacA s1 was the only predictive factor for PUD (OR=4.19; 95% CI 1.95-8.98). The presence of the less virulent strain vacA s2 was related to GERD (OR=8.59; 95% CI 2.85-25.91). Our results support the hypothesis that virulent strains may protect against the development of GERD.     

A Population-Based Epidemiologic Study of Helicobacter Pylori Infection and its Association with Systemic Inflammation

Background:  Infection with Helicobacter pylori is associated with a variety of non-gastrointestinal sequelae. These may be mediated by an increase in systemic inflammation. We assessed if serologic evidence of infection with H. pylori is associated with increased serum C-reactive protein (CRP) levels.
Methods:  The study design consisted of a randomly selected, cross-sectional population-based study of 2633 individuals phenotyped in 1991, of whom 2361 participants provided serum samples to permit measurement of H. pylori 's serologic status and CRP levels.
Results:  Male gender (odds ratio (OR): 1.65; 95% confidence interval (CI): 1.23–2.21), age (OR per year: 1.05; 95% CI: 1.04–1.06), height (OR per meter: 0.05; 95% CI: 0.01–0.24), current smoking habit (compared with never smokers, OR: 1.46; 95% CI: 1.13–1.88), and less affluent socioeconomic status were associated with increased odds of being seropositive for H. pylori . Helicobacter pylori infection was associated with increased risk of having an elevated serum CRP (above 3 mg/L) after adjustment for gender, age, height, smoking status, and socioeconomic status (OR: 1.32; 95% CI: 1.05–1.67). Similar associations were seen using a threshold for elevated serum CRP of greater than 1 mg/L.
Conclusions:  Our data suggest that infection with H. pylori is associated with increased systemic inflammation. This suggests one potential mechanism to explain the extra-gastrointestinal conditions associated with H. pylori infection.     

Is the Association Between Helicobacter pylori and Gastric Cancer Confined to CagA‐Positive Strains?

BACKGROUND: Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk. MATERIALS AND METHODS: In a hospital-based case-control study, we collected sera from 100 case patients with a newly diagnosed gastric adenocarcinoma and 96 control patients with diseases unrelated to H. pylori status. Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA were detected by immunoblot. Logistic regression was used to obtain odds ratios (ORs) as estimates of relative risk, adjusted for potential confounding. RESULTS: Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA. The corresponding numbers among the controls were 58% and 55%, respectively. ELISA positivity was associated with an increased risk of gastric adenocarcinoma compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95% CI 1.9-8.2). The OR was 7.4 (95% CI 3.3-16.6) for CagA-positive relative to CagA-negative subjects. Among ELISA-positive subjects the presence of CagA antibodies increased the risk 3.6 times (95% CI 1.2-11.1). ELISA-positive CagA-negative infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0-17.0) compared to no infection (ELISA-negative and CagA-negative). CONCLUSIONS: Although patients with antibodies to CagA have the greatest risk of developing gastric cancer, those with CagA-negative infections run a significantly greater risk than uninfected persons.     

Diverse H. pylori strains,IL-10 promoter polymorphisms with high morbidity of gastric cancer in Hexi area of Gansu Province,China

In Hexi area of Gansu Province, people have a higher susceptibility of gastric cancer than people in the rest area of China. There is substantial geographic variation in the incidence of gastric cancer. In this article, the present author explored the roles of H. pylori infection and IL-10 promoter polymorphisms in development of gastric cancer in this area. A total of 304 participants were admitted to our study, and they were divided into two groups: control group and case group. Blood samples from all subjects were collected for gene extraction using DNA extraction kits. IL-10 polymorphisms were determined by SNaPshot Multiplex. To test H. pylori infection and its typing H. pylori antibody Immunoblotting Kits were used. This research suggested that environmental factor played an important role in the pathogenesis of gastric carcinoma in the area, H. pylori infection increased the risk of gastric cancer (OR = 2.612, 95% CI 1.636-4.170) and subject with H. pylori I-type positive was at significantly higher risk for progression to gastric cancer (OR = 4.712, 95% CI 2.656-8.537). For subjects with the ATA/GCC or GCC/GCC haplotype of the IL-10-1082/-819/-592 polymorphism relative to the ATA/ATA haplotype group, the risk of gastric cancer development was significantly increased. It has been demonstrated that the presence of IL-10-819 C alleles and IL-10-592 C alleles was associated with an increased risk for gastric cancer development in H. pylori-infected patients and IL-10 promoter polymorphisms and H. pylori have a synergistic effect on gastric cancer in Hexi population.     

Epidemiological study on Helicobacter pylori infection and extragastroduodenal disorders in Polish population.

An association between Helicobacter pylori (H. pylori) infection and extragastroduodenal disorders (EGDD) is still not clear. The aim of the study was to investigate the relationship between H. pylori infection and the symptoms of coronary artery disease (CAD), facial dermatological changes (FDC), gastroesophageal reflux diseases (GERD), and periodontal diseases (PD) in Polish population. The study was performed between 1996-1999 year on 7,060 adult inhabitants of municipal area of Krakow (aged 18-76, mean 46.3 year; 55.8% female, 44.2% male): 2,204 subjects with EGDD and 4,856 without symptoms of EGDD. Each patient responded to a detailed questionnaire under supervision of medical staff. The H. pylori status was assessed non-invasively using urea breath test (UBT) with capsulated low-dose 13C-UBT (38 mg). Exclusion criteria were: recent H. pylori eradication, treatment with PPI, bismuth and/or antibiotics in the last 4 weeks. Four groups of cases with EGDD symptoms were selected. Within each group exclusively only one of studied symptoms was recorded. The study included 328, 138, 688, and 1,050 patients with CAD, FDC, GERD and PD, respectively. For each studied group an age and sex-matched asymptomatic controls were selected (897, 387, 1,083, and 2,489 control patients). Results: Overall H. pylori infection rate was 69,9% (in 71.4% of 2,204 cases and in 69.31% of 4,856 controls). In CAD group: 68% of 328 cases were H. pylori (+ve) vs. 70% H. pylori (+ve) of 897 controls. An association was not significant: OR = 0.93 (95% CI, 0.72-1.20). In 138 of FDC cases, 59% were H. pylori (+ve) vs. 71% H. pylori (+ve) in 387 controls showing the lack of positive association; OR = 0.60 (95% CI, 0.42-0.87). In GERD, 69% of 688 cases were H. pylori (+ve) vs. 73% of 1,083 H. pylori (+ve) controls and negative association was observed; OR=0.80 (95% CI, 0.65-1.00). In 1,050 of PD cases 75% were H. pylori (+ve) vs. 68% H. pylori (+ve) of 2,489 controls; positive association was significant; OR = 1.4 (95% CI, 1.16-1.68). We conclude that in the studied Polish population, no positive association exists between H. pylori positivity and CAD, FDC or GERD possibly due very high overall H. pylori infection rate. The only positive link observed between H. pylori infection and periodontal disease may reflect direct "in situ" H. pylori pathological action of H. pylori in oral cavity. It is not excluded that periodontal diseases may facilitate the H. pylori oro-gastric transmission and colonisation of the bacteria in the digestive tract.     

Helicobacter pylori, ethnicity, and the gastroesophageal reflux disease spectrum: a study from the East

BACKGROUND: Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored. AIMS: We estimated the strength of the association between H. pylori, ethnicity, and the gastroesophageal reflux disease (GERD) spectrum, including Barrett's esophagus, in Asian patients presenting for endoscopy in a tertiary referral center. METHODS: Prospectively, we studied 188 consecutive patients with GERD, short- and long-segment Barrett's esophagus, and controls. All patients underwent gastroscopy with gastric biopsies to assess H. pylori, gastritis, and atrophy. CagA status and H. pylori infection were determined by immunoblot assay. RESULTS: The overall prevalence of H. pylori infection was 52.1% (of which 77.6% were cagA(+)) and was lowest in the long-segment Barrett's esophagus group (36.7%) (p = .048). When Barrett's esophagus was present, the length of abnormality was 44.8% shorter in the presence of H. pylori (p = .015). Indians had the highest prevalence of H. pylori (75%) and Malays the lowest (19.6%) (p < .001). In Indians, increased prevalence of H. pylori and cagA-positive strains was associated with reduced severity of GERD (p < .004 and p < .001, respectively), a trend not apparent in the other races. Corpus atrophy, which was almost exclusively associated with H. pylori, was highest in Indians as compared to the other races (p = .013). CONCLUSIONS: Presence of H. pylori was associated with a reduced severity of GERD spectrum disease in Asians, especially Indians. H. pylori infection may protect against complicated reflux disease via induction of corpus atrophy.     

Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden

ABSTRACT: BACKGROUND: Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related toinfection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori,CagA and VacA, have been associated with these sequelae of the infection. In this study, totalDNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes. RESULTS: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/dayregions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals usingPCR and sequencing. Analysis of a possible association between cagA and vacA genotypesand gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the samebiopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs wasassociated with atrophy in the gastric mucosa. No statistically significant relation betweenvacA genotypes and gastroduodenal pathogenesis was observed. CONCLUSIONS: The results of this study indicate that cagA genotypes may be important determinants in thedevelopment of gastroduodenal sequelae of H. pylori infection. In contrast to other studies,vacA genotypes were not related to disease progression or outcome. In order to fullyunderstand the relations between cagA, vacA and gastroduodenal pathogenesis, themechanisms by which CagA and VacA act and interact need to be further investigated.     

Toll-Like Receptor 4 +3725 G/C Polymorphism, Helicobacter pylori Seropositivity, and the Risk of Gastric Atrophy and Gastric Cancer in Japanese

Background:  Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms were reported to be a risk factor of gastric carcinoma or its precursors in Caucasian and Indian population, but these polymorphisms are absent in Japanese. We investigated the associations of TLR4 +3725 G/C polymorphism, another functional polymorphism of TLR4 , with risk of gastric cancer and gastric atrophy in Japanese.
Materials and Methods:  Study subjects were 583 histologically diagnosed gastric cancer patients and age- and sex-matched 1592 control outpatients, who visited Aichi Cancer Center Hospital from 2001 to 2005. Serum anti- H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.
Results:  Among the seropositive subjects, the age- and sex-adjusted OR of gastric atrophy was 1.17 (95%CI: 0.91–1.50) for G/C , 1.20 (95%CI: 0.76–1.89) for C/C , and 1.18 (95%CI: 0.93–1.49) for G/C + C/C relative to G/G genotype. The age- and sex-adjusted OR of severe gastric atrophy among H. pylori seropositive subjects was 1.43 (95%CI: 0.99–2.06) for G/C , 1.47 (95%CI: 0.76–2.88) for C/C , and 1.43 (95%CI: 1.01–2.04) for G/C + C/C . The OR of gastric cancer compared with gastric atrophy controls was not statistically significant.
Conclusion:  Our study found that TLR4 +3725 G/C polymorphism was a risk factor of severe gastric atrophy in H. pylori seropositive Japanese. Our results underscored the significance of the variations in host innate immunity due to TLR4 polymorphism as genetic predispositions to gastric precancerous lesions in Eastern Asian populations with the same backgrounds.     

Helicobacter pylori seropositivity and risk of lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.     

cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA- strains

cagA+ Helicobacter pylori (HP) infection is associated with an increased risk of distal gastric cancer. Previous studies investigating the effect of HP infection on prostaglandin E2 (PGE2) levels have not differentiated between cagA+ and cagA- strains and consequently have produced contradictory results. The aim was to investigate the effect of cagA+ strains on PGE2 and enhance the understanding of the mechanisms leading to gastric diseases. Hundred patients without peptic ulcers and not on medication were recruited (one later excluded) from endoscopy clinics: six biopsies were obtained from each patient. PGE2, colonization density and histology were determined. In addition, HP status was assessed by histology, CLOtest and culture with cagA+ being determined by PCR. Sixty-nine patients were HP- and 30 HP+ (10 cagA+, 18 cagA-, 2 undetermined). In age and sex-matched patients, PGE2 was significantly greater (P = 0.04) in HP+ (37.2 +/- 1.2 pg/mg per 20 min) than in HP- (22.6 +/- 1.2). In patients without atrophy, those infected with cagA+ had significantly higher (P = 0.03) PGE2 levels (53 +/- 1.1) than HP- patients (22.6 +/- 1.1) and greater levels (P = 0.29) than cagA- patients (35 +/- 1.3). In conclusion, the increased levels of PGE2 in the presence of cagA+ infection could be an important factor by which cagA+ strains enhance the gastric mucus layer protective functions leading to established colonization, gastritis and increased risk of gastric cancer. However, further evaluation with a large-scale multi-centre study is required to substantiate this hypothesis.     

The effects of genetic polymorphisms of IL-1 and TNF-A on Helicobacter pylori-induced gastroduodenal diseases in Korea

OBJECTIVE: To evaluate whether or not genetic polymorphism of IL-1B, IL-1RN, and TNF-Alpha is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection. METHODS: This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first-degree gastric cancer relative (GCR). IL-1Beta-511 and TNF-A-308 biallelic polymorphism were genotyped by 5' nuclease polymerase chain reaction (PCR) assays, and PCR-restriction fragment length polymorphism (PCR-RFLP). IL-1RN penta-allelic variable number of tandem repeats was genotyped by PCR. RESULTS: There was no difference in the genetic polymorphism of IL-1Beta-511, IL-1RN and TNF-A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL-1B-511 C/T (OR: 0.5, 95% CI: 0.3-0.7) and T carrier (OR: 0.6, 95% CI: 0.4-0.8) were lower in the H. pylori-positive BGU patients. The IL-1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1-28.5) in the H. pylori-positive GCR. There was no significance in the polymorphism of TNF-Alpha-308 regardless of H. pylori-induced gastroduodenal diseases. CONCLUSIONS: The IL-1Beta-511 T-carrier polymorphism has a negative effect on the development of H. pylori-positive BGU, and high frequency of IL-1RN 2/2 was found in the H. pylori-positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori-induced gastroduodenal diseases in Korea.     

Decreased Prevalence of Helicobacter pylori Infection in Gastroesophageal Reflux Disease

Background.   An increased incidence of reflux esophagitis has been reported after eradication of H. pylori in patients with duodenal ulcer. To determine if H. pylori is associated with lower rates of esophagitis, we studied the prevalence of H. pylori infection in patients with and without reflux esophagitis and a subgroup of patients with concomitant peptic ulcer disease.
Methods.   Patients who underwent esophagogastroduodenoscopy and had diagnostic testing for H. pylori over a 30-month period were studied. H. pylori infection was determined by rapid urease testing, gastric histopathology, or serology. Reflux esophagitis was determined by endoscopic and/or histologic criteria.
Results.   Of 514 patients, 39.5% had H. pylori infection and 22.2% had reflux esophagitis. The prevalence of H. pylori infection in patients with reflux esophagitis was 30.7%, compared with 42.0% in patients without esophagitis ( p = 0.039). The odds ratio for esophagitis risk with H. pylori infection was 0.61 (95% CI, 0.39–0.95). Neither patient age nor gender affected H. pylori prevalence. In patients with duodenal ulcer, H. pylori was present in 36.4% of patients with esophagitis and in 69.2% of patients without esophagitis ( p = 0.018). The odds ratio for esophagitis with H. pylori infection in these patients was 0.25 (95% CI, 0.09–0.73).
Conclusions.   Our study demonstrates that H. pylori infection is significantly less prevalent in patients with reflux esophagitis and may protect against its development. In duodenal ulcer patients, this effect was more dramatic. Further study is required to confirm these findings and elucidate mechanisms underlying possible beneficial effects of H. pylori.     

The GSTM1 Null Genotype Increased Risk of Gastric Cancer: A Meta-Analysis Based on 46 Studies

Background

Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk.

Methods

This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren’s classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength.

Results

A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P_{heterogeneity}<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P_{heterogeneity} = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P_{heterogeneity}=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P_{heterogeneity}=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren’s classification did not modify the association.

Conclusions

In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.     

Helicobacter pylori genotyping and sequencing using paraffin-embedded biopsies from residents of colombian areas with contrasting gastric cancer risks

Background:   cagA -positive and vacA s1 and m1 genotypes of Helicobacter pylori are associated with an elevated risk of gastric cancer (GC). We determined these genotypes using paraffin-embedded gastric biopsy specimens harvested from infected individuals and compared genotype distributions in two Colombian populations residing in geographic regions with a high and low incidence of GC.
Methods:   DNA from paraffin-embedded gastric biopsies from 107 adults was amplified using primers specific for cagA , for the cag 'empty site', for the s and m alleles of vacA , and for H. pylori 16S rRNA.
Results:   H. pylori infection was detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in 78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were not significantly associated with a particular geographic area. The vacA m1 allele and s1m1 genotypes were more common in the area of high risk for GC ( p =  .037 and p  = .044, respectively), while the vacA m2 allele and s2m2 genotypes were more prevalent in the low-risk area. The prevalence of the combination of cagA -positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk areas, respectively ( p =  .011).
Conclusions:  H. pylori cagA and vacA genotyping from paraffin-embedded gastric biopsies permitted reliable typability and discrimination. The more virulent cagA- positive s1m1 strains, as well as vacA m1 genotype, were more prevalent in high risk than in low risk areas, which may contribute to the difference in GC risk between those two regions.