Interleukin-8-251A/T polymorphism and Helicobacter pylori infection influence risk for the development of gastric cardiac adenocarcinoma in a high-incidence area of China

Polymorphisms in cytokine genes may contribute to increased susceptibility to different cancers. The aim of this paper is to investigate the association of IL-8-251A/T polymorphism and Helicobacter pylori (H. pylori) infection with the risk of developing gastric cardiac adenocarcinoma (GCA) in the south of Taihang Mountain, a high-incidence area of esophageal cancer in China. The IL-8-251 A/T polymorphism was genotyped in 519 cases of GCA and 504 healthy controls. The H. pylori infection in GCA patients and controls was detected by rapid urease test (RUT), histopathology or ¹⁴C-urea breath test (¹⁴C-UBT). The results showed that family history of upper gastrointestinal cancer (UGIC) and H. pylori infection significantly increased the risk of developing GCA. The overall genotype and allelotype distributions of IL-8 promoter SNPs in GCA patients were significantly different from those in healthy controls. Compared with TT genotype, AA genotype significantly elevated the risk of developing GCA. The stratification analysis revealed that, compared with the TT genotype, the AA genotype significantly elevated the risk of developing GCA in both positive family history of UGIC and H. pylori infection subgroups. This study provides evidence to support a relationship of increased susceptibility to GCA in individuals of the south Taihang Mountain region with IL-8 251 AA genotype, especially for those individuals who have family history of UGIC or H. pylori infection.     

Seroreactivity to 19.5-kDa antigen in combination with absence of seroreactivity to 35-kDa antigen is associated with an increased risk of gastric adenocarcinoma

Background. Only a minority of those infected with Helicobacter pylori will develop gastric cancer. Stratification of H. pylori strains based on carcinogenic potential will provide a basis for selective surveillance and eradication therapy. We studied the anti‐H. pylori antibody profile in Asian patients with gastric adenocarcinoma to identify any H. pylori antigen that may be associated with an increased or decreased risk of gastric carcinoma. Patients and Methods. A case‐control study comparing the seroprevalence of antibodies with various H. pylori antigens in Singaporeans with gastric adenocarcinoma and the normal Singaporean population was carried out using both conventional immunoglobulin (Ig) G enzyme‐linked immunosorbent assay (ELISA) and Western blot immunoassay. Results. The seroprevalence among 44 gastric adenocarcinoma cases (70.5% males, mean age 66.7 ± 13.5 years) and 261 controls (49.8% males, mean age 61.5 ± 4.1 years) was 90.9% vs. 50.2% by IgG ELISA. In the H. pylori‐positive male population, those suffering from gastric adenocarcinoma had significantly lower seroreactivity to the 35‐kDa antigen compared with asymptomatic controls (p = .0198, OR = 3.79, 95% CI 1.24–11.61). Seropositivity to the 19.5 kDa antigen was also found to be associated with the presence of gastric adenocarcinoma in Singaporean males (p = .022, OR = 4.17, 95% CI 1.22–14.28). A ‘high‐risk’ phenotype consisting of absence of a band at 35‐kDa in combination with the presence of a band at 19.5‐kDa was significantly associated with the presence of gastric adenocarcinoma (p = .002, OR = 3.7, 95% CI 1.6–8.6). Conclusions. Stratification of H. pylori strains based on their potential for carcinogenesis, such as those strains that are seropositive for the 19.5 kDa antigen and seronegative for the 35‐kDa antigen, may provide a basis for selective eradication of H. pylori infection and future vaccine development.     

Helicobacter pylori infection and gastric cardia cancer in Chaoshan region

Helicobacter pylori (H. pylori) infection represents the most important risk factor for gastric cancer, while its association with gastric cardia cancer (GCC) has not been recognized yet. In this current study, we aim to investigate the status of H. pylori infection in the gastric cardia tissue samples from high-risk populations in Chaoshan littoral region, and the relationship between H. pylori infection and chronic inflammation as well as the proliferative activity of the gastric cardia epithelial cells. A total of 706 gastric cardia biopsy specimens were obtained from 372 GCC cases and 334 tumor-free controls in Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. Immunohistochemistry and Giemsa staining were employed for the verification of H. pylori infection. H. pylori infection rate was significantly higher in GCC (81.5%, P < 0.01) and gastric carditis (80.1%, P < 0.01) in comparison with that in the healthy group (34.8%). A significant higher prevalence of chronic inflammation was found in H. pylori+ samples (96.9%) than that in H. pylori− specimens (80.5%) (P < 0.01). To explore the possible role of H. pylori infection-related chronic inflammation in the GCC, we found that the expression of Ki-67 was progressively increased in tissues with chronic inflammation degrees from normal to severe inflammation (P < 0.01). Collectively, these results suggest that persistent H. pylori infection and the related chronic inflammation may contribute to the high incidence of GCC in Chaoshan littoral.     

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status

Background: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. Materials and Methods: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. “Atrophic” pepsinogen was defined as pepsinogen‐I < 70 ng/mL and pepsinogen‐I/II ratio <3. Other levels of pepsinogen were defined as “normal”. Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. Results: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori‐seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori‐seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with “normal” pepsinogen, but inversely correlated in those with “atrophic” pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. Conclusions: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening.     

Helicobacter pylori-negative gastric cancer in South Korea: incidence and clinicopathologic characteristics

Background and Aim: It is difficult to determine the exact incidence rate of Helicobacter pylori (H. pylori) infection‐negative gastric cancer (HPIN‐GC) because H. pylori detection rates decrease with the progression of gastric atrophy and intestinal metaplasia. The aim of this study was to evaluate the incidence and clinicopathologic characteristics of HPIN‐GC in South Korea. Methods: Helicobacter pylori infection status was evaluated by histology, a rapid urease test (CLO test), culturing, serology, and history of H. pylori eradication for 627 patients with gastric cancer. Current H. pylori infection was defined as positive results from histology, the CLO test, and culturing. Previous H. pylori infection was defined as negative in all three biopsy‐based tests and positive serology or history of H. pylori eradication. Patients were considered to be negative for H. pylori infection if all results from five methods were negative. However, patients who were found to have severe gastric atrophy by the serum pepsinogen test or metaplastic gastric atrophy by histology were assumed to have had a previous H. pylori infection even if results from other tests for H. pylori infection were all negative. Results: The number of patients with gastric cancer with current or previous H. pylori infection was 439 (70.0%) and 154 (24.6%), respectively. The rate of HPIN‐GC occurrence was 5.4% (n = 34). Sex, age, Lauren type, location of the tumor, and treatment modalities were not different according to H. pylori infection status. However, HPIN‐GC had a more advanced pT classification (T3/T4; 51.9 vs 31.1%, p = .025) and a more advanced stage (more than stage I; 63 vs 41.3%, p = .027) than H. pylori‐positive gastric cancer. Conclusion: At least 5.4% cases of gastric cancer were H. pylori negative among South Korean patients. HPIN‐GC looks like to have a poorer prognosis than H. pylori‐positive cases.     

Statistical model of the interactions between Helicobacter pylori infection and gastric cancer development

Background. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer. Methods. To find direct and indirect interactions between H. pylori and different histological variables, log‐linear analyses were used on a case–control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used. Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined. Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.     

Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer

Background and Aims: To determine genome‐wide DNA methylation profiles induced by Helicobacter pylori (H. pylori) infection and to identify methylation markers in H. pylori‐induced gastric carcinogenesis. Methods: Gastric mucosae obtained from controls (n = 20) and patients with gastric cancer (n = 28) were included. A wide panel of CpG sites in cancer‐related genes (1505 CpG sites in 807 genes) was analyzed using Illumina bead array technology. Validation of the results of Illumina bead array technique was performed using methylation‐specific PCR method for four genes (MOS, DCC, CRK, and PTPN6). Results: The Illumina bead array showed that a total of 359 CpG sites (269 genes) were identified as differentially methylated by H. pylori infection (p < .0001). The correlation between methylation‐specific PCR and bead array analysis was significant (p < .0001, Spearman coefficient = 0.5054). Methylation profiles in noncancerous gastric mucosae of the patients with gastric cancer showed quite distinct patterns according to the presence or absence of the current H. pylori infection; however, 10 CpG sites were identified to be hypermethylated and three hypomethylated in association with the presence of gastric cancer regardless of H. pylori infection (p < .01). Conclusions: Genome‐wide methylation profiles showed a number of genes differentially methylated by H. pylori infection. Methylation profiles in noncancerous gastric mucosae from the patients with gastric cancer can be affected by H. pylori‐induced gastritis. Differentially methylated CpG sites in this study needs to be validated in a larger population using quantitative methylation‐specific PCR method.     

Imbalance of Gastrointestinal Microbiota in the Pathogenesis of Helicobacter pylori‐Associated Diseases

The development of new nucleotide sequencing techniques and advanced bioinformatics tools has opened the field for studying the diversity and complexity of the gastrointestinal microbiome independent of traditional cultural methods. Owing largely to the gastric acid barrier, the human stomach was long thought to be sterile. The discovery of Helicobacter pylori, the gram‐negative bacterium that infects upwards of 50% of the global population, has started a major paradigm shift in our understanding of the stomach as an ecologic niche for bacteria. Recent sequencing analysis of gastric microbiota showed that H. pylori was not alone and the interaction of H. pylori with those microorganisms might play a part in H. pylori‐associated diseases such as gastric cancer. In this review, we summarize the available literature about the changes of gastrointestinal microbiota after H. pylori infection in humans and animal models, and discuss the possible underlying mechanisms including the alterations of the gastric environment, the secretion of hormones and the degree of inflammatory response. In general, information regarding the composition and function of gastrointestinal microbiome is still in its infancy, future studies are needed to elucidate whether and to what extent H. pylori infection perturbs the established microbiota. It is assumed that clarifying the role of gastrointestinal communities in H. pylori‐associated diseases will provide an opportunity for translational application as a biomarker for the risk of serious H. pylori diseases and perhaps identify specific organisms for therapeutic eradication.     

A population-based study of Helicobacter pylori infection in Chinese children resident in Hong Kong: prevalence and potential risk factors

Background: Data of Helicobacter pylori prevalence in children and its risk factors provide clues to the health authority to estimate burden of H. pylori‐associated diseases usually encountered in adulthood and facilitate healthcare planning. Materials and Methods: A cross‐sectional population‐based study was conducted in Chinese children in elementary and high schools. Schools were selected from all three major areas of Hong Kong. H. pylori infection was defined by a positive ¹³C‐urea breath test. Study subjects were stratified into six age groups for estimation of prevalence. Potential risk factors were analyzed from data of self‐administered questionnaires. Results: A total of 2480 children (aged 6–19, male: 47.3%) participated in the study. Overall, 324 (13.1%) were positive for H. pylori. There was no difference in prevalence between sexes, and no statistical trend in the prevalence across the six age groups. Multivariate logistic regression identified lack of formal education of mother (OR = 2.43, 95%CI 1.36–4.34), family history of gastric cancer (OR = 2.19, 95%CI 1.09–4.41), and household member > 5 (OR = 1.57, 95%CI 1.12–2.19) to be positively associated with H. pylori infection in our children. Conclusions: The H. pylori prevalence of Hong Kong children is comparable to the data of developed countries. The association with family history of gastric cancer justifies further study to investigate the cost‐benefit of community screening program for such children to decrease the incidence of gastric cancer in adulthood.     

Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori

Background and Aims: The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. Methods: The subjects were 18 early‐stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. Results: The average diameter of gastric cancer was smaller and Ki‐67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Conclusion: Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer.     

Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer

Background. Helicobacter pylori infection is usually acquired during childhood and is a known risk factor for the development of gastric malignancies in adulthood. It has been reported that early age at first infection may determine a neoplastic outcome in adults. The purpose of this study was to determine the prevalence of Helicobacter pylori infection in children residing in areas with high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate whether differences in the age of acquisition of H. pylori infection were present in the two populations. Materials and Methods. The study sample was based on a census taken in 1999. Using the ¹³C‐urea breath test, we compared the prevalence of H. pylori infection among children aged 1–6 years. Results. Among 345 children in Pasto, 206 (59.7%) were H. pylori‐positive, compared with 188 (58.6%) among 321 children in Tumaco. The two populations share a common pattern of very early age at infection and marked increase in prevalence during the first 4 years of life. No differences in any one year were observed when comparing the two groups. Conclusions. The prevalence of infection was similarly high and increased with age in both populations. In these populations the age of acquisition of H. pylori after 1 year of age does not appear to be a primary factor responsible for the differences in the rates of gastric cancer incidence in adults. Previous findings in adults showed lower prevalence of the most virulent genotypes in Tumaco compared to Pasto, and bacterial virulence may play a key role in determining cancer outcome.     

Decreasing trend of Helicobacter pylori infection in children with gastrointestinal symptoms from Buenos Aires, Argentina

Background: Helicobacter pylori infection is declining in developed and developing countries. The aim of this study was to retrospectively evaluate over an 8‐year period the rate of H. pylori infection in children with gastrointestinal symptoms from Buenos Aires, Argentina. Materials and Methods: We reviewed the records of children referred from 2002 to 2009 to the gastroenterology unit of the Children Hospital “Superiora Sor Maria Ludovica” for evaluation of upper gastrointestinal signs and symptoms in which the ¹³C‐urea breath test was performed to diagnose H. pylori infection and a sociodemographic questionnaire was obtained. Results: Records of a total of 1030 children and adolescents with a mean age of 9.99 years were included in the analysis. We found an H. pylori prevalence of 41.2% (95% CI, 36.9–46.0%) for the triennium 2002–2004, dropping to 26.0% (95% CI, 20.7–31.8%) in the triennium 2007–2009. Conclusion: Our results showed a significant decrease in H. pylori infection rates from children referred for upper gastrointestinal symptoms evaluation from 2002 to 2009, following the H. pylori epidemiologic trend reported in other countries.     

Preventive effects of Cladosiphon fucoidan against Helicobacter pylori infection in Mongolian gerbils

Background. Recently, the acquisition by Helicobacter pylori of resistance to antibiotics has become a serious problem. Therefore, nonantibiotic substances are required to diminish H. pylori‐induced gastric lesions. In the present study, the effects of Cladosiphon fucoidan were examined in terms of H. pylori attachment to porcine gastric mucin in vitro and Helicobacter pylori‐induced gastritis in vivo. Methods. The inhibitory effect of Cladosiphon fucoidan and other polysaccharides on H. pylori attachment to porcine gastric mucin was assayed in vitro with mucin‐coated microtiter plates. The effect of Cladosiphon fucoidan on H. pylori‐induced gastritis was examined in vivo using Mongolian gerbils. H. pylori‐inoculated gerbils were given fucoidan in drinking water. Six weeks after H. pylori‐inoculation, gerbils were sacrificed for macroscopic and microscopic examination of gastric lesions and counting of viable H. pylori in the gastric mucosa. Results. Cladosiphon fucoidan inhibited the H. pylori attachment to porcine gastric mucin at pH 2.0 and 4.0. Two other sulfated polysaccharides, Fucus fucoidan and dextran sulfate sodium, also inhibited the attachment but only at pH 2.0. Inhibitory effects of these three sulfated polysaccharides were not observed at pH 7.2 and nonsulfated polysaccharides, such as mannan and dextran, exerted no influence at any pH. In the in vivo experiment, the H. pylori‐induced gastritis and the prevalence of H. pylori infected animals were markedly reduced by fucoidan in a dose‐dependent manner, at doses of 0.05 and 0.5% in the drinking water. Conclusion. Cladosiphon fucoidan may deserve particular attention as a safe agent that can prevent H. pylori infection and reduce the risk of associated gastric cancer.     

Effect of Helicobacter pylori infection on Barrett's esophagus and esophageal adenocarcinoma formation in a rat model of chronic gastroesophageal reflux

Objectives: To investigate the relationship between Helicobacter pylori infection and Barrett’s esophagus (BE), a rat model of chronic gastroesophageal reflux with H. pylori infection was established and the degree of inflammation, incidence of BE and esophageal adenocarcinoma (EA) were evaluated. Methods: Eight‐week‐old male specific‐pathogen‐free SD rats were divided into five groups randomly: pseudo‐operation group; esophagojejunum anastomosis (EJA) group; EJA with H. pylori infection group; EJA with H. pylori infection and celecoxib‐treated group; EJA with celecoxib‐treated group. Rats were kept for 30 weeks after surgery. Esophageal lesion was evaluated grossly and microscopically. The expression of COX‐2 and CDX2 was determined by RT‐PCR and immunohistochemistry staining. The level of PGE₂ was assessed by enzyme‐linked immunosorbent assay. Results: Esophageal mucosal injury in the group of EJA with H. pylori infection was decreased than that in EJA group (p < .05). The incidence of BE and EA in rats undergoing EJA with H. pylori infection was increased than in rats undergoing EJA with no statistical difference. Celecoxib treatment decreased the incidence of EA in rats undergoing EJA with H. pylori infection (p < .05). The expression of CDX2 mRNA was decreased in rats with H. pylori infection or treated with celecoxib than in the rats of pseudo‐operation group (p < .05). When compared with those in rats of pseudo‐operation group, the expression of COX‐2 mRNA and the level of PGE₂ were upregulated in rats undergoing EJA irrespective of H. pylori infection (p < .05) and downregulated in rats treated with celecoxib (p < .05). When H. pylori colonized in esophagus, the severity of inflammation and the incidence of BE and EA were increased significantly. Higher levels of COX‐2 expression and PGE₂ were detected in rats with esophageal H. pylori colonization. Conclusions: When H. pylori infect in stomach, it may reduce the severity of inflammation. However, when colonizes in esophagus, H. pylori increases the severity of esophageal inflammation and the incidence of BE and EA. Celecoxib administration attenuates the incidence of EA by inhibiting COX‐2 expression.     

Histology of gastritis and Helicobacter pylori infection in Thailand: a nationwide study of 3776 cases

Background. Dyspepsia is a very common problem in Thailand. Etiology of gastritis, incidence of Helicobacter pylori and mode of transmission of Helicobacter pylori infection in the country was proposed. Methods. A nation‐wide study of gastric biopsy in 3776 dyspeptic patients from six different geographic regions for incidence of gastritis, type of gastritis, incidence of H. pylori infection, gastric atrophic change and intestinal metaplasia in three age‐groups of each region was done. Results. 58.7% of dyspeptic patients had histological gastritis. Pangastritis was the most common type (77.3%) with mostly mild active inflammation (60.6%) and was found most commonly in the age group 31–60 years. Incidence of gastritis was slightly lower in the coastal and peninsular community compared with the mountain, jungle, semiarid plateau and fertile plain communities. Geographic factor, socioeconomic status and dietary habit were proposed to be important factors in inducing gastritis. H. pylori infection was found in 48.2% of dyspeptic patients with high incidence in the age‐group 31–60 years (63.7%) and 98.2% of H. pylori infection was found to be associated with gastritis. Semi‐arid plateau, mountain, jungle and fertile plain communities had high incidences of H. pylori infection varying from 54.0 to 67.1% while the coastal and peninsular communities had low incidences of 32%. Oral to oral spread is proposed to be the mode of bacterial transmission. Incidences of gastric atrophic change and intestinal metaplasia were low in this country and were found in 11.6% and 8.2% of subjects, respectively, with no significantly different distribution in geographic regions. Type I or intestinal type was found to be the most common type of intestinal metaplasia.     

Gastric mucosal blood flow changes in Helicobacter pylori infection and NSAID-induced gastric injury

Background. The impact of H. pylori infection on gastric mucosal blood flow and NSAID‐induced gastric damage is unclear. Aim. To study the effects of H. pylori infection on gastric mucosal blood flow, both at basal conditions and after NSAID exposure, and its relation with mucosal damage and nitric oxide production. Methods. Gastric mucosal blood flow, nitric oxide production and gastric damage were assessed in time after H. pylori SS1 or E. coli inoculation in mice. Experiments were conducted in basal conditions or after oral exposure to indomethacin (20 mg/kg). Results. H. pylori infected mice exhibited a significant increase in gastric blood flow and gastric nitric oxide production 1 week after infection, but those parameters returned to basal levels by 4 weeks. NSAID challenge elicited a similar reduction in gastric blood flow [25–35%] in H. pylori‐infected and control animals. However, only 1 week H. pylori‐infected mice, which exhibited a significant baseline hyperemia, were able to maintain gastric blood flow values within the normal range after NSAID exposure. NSAID‐induced gastric damage was increased in H. pylori‐infected mice by 4 weeks, but not 1 week after infection. Conclusions. Underlying H. pylori infection aggravates acute NSAID‐induced gastric damage. However, at early phases, gastric hyperemia associated with increased nitric oxide production may exert some protective role.     

Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori-associated gastroduodenal diseases

Background. Polymorphisms in the promoter region of the proinflammatory cytokine, interleukin (IL)‐6 have been related to several chronic inflammatory diseases. Inter‐individual variation in the severity of gastric inflammation may be important in determining the clinical outcome of an Helicobacter pylori infection and relate to polymorphisms in this region. Materials and Methods. We studied H. pylori‐infected patients with duodenal ulcer or gastric cancer. In addition six gastric cancer cell lines, AGS, SNU‐668, MKN‐1, MKN‐7, MKN28 and KATOIII, were cocultured with both cag pathogenicity island‐positive and ‐negative H. pylori. Single nucleotide polymorphisms at positions ?174, ?572, and ?597 in the IL‐6 promoter region were identified by PCR‐RFLP. The IL‐6 production from the cancer cells was determined by ELISA. Results. Sixty patients with gastric cancer and 60 with duodenal ulcer were studied. The alleles at positions ?174 and ?597 were closely linked (?174G/?597G or ?174C/?597A) regardless of the ethnic group or disease presentation. There was no difference in the allele frequency at any of the sites among patient groups. H. pylori‐induced IL‐6 production from the gastric cancer cell lines was also independent of the IL‐6 polymorphisms or the presence of the cag pathogenicity island. Conclusions. The genetic polymorphisms in IL‐6 can be attributable to ethnicity and appear to be independent of the clinical outcome of an H. pylori infection.     

Helicobacter pylori Infection – A Boon or a Bane: Lessons from Studies in a Low‐Prevalence Population

Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori‐infected non‐Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.     

Helicobacter pylori infection,mucosal atrophy and intestinal metaplasia in Asian populations: a comparative study in age-, gender- and endoscopic diagnosis-matched subjects

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races. Materials and Methods. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori‐related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori‐positive cases (n = 120, 109, 145, 80, respectively) and H. pylori‐negative cases (n = 55, 66, 30, 95, respectively). Results. Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori‐positive Japanese subjects than in H. pylori‐positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori‐negative subjects belonging to the different Asian populations examined. Conclusions. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.     

CpG island hypermethylation of tumor-suppressor genes in H. pylori-infected non-neoplastic gastric mucosa is linked with gastric cancer risk

Background and aim: Gastric carcinogenesis involves CpG island hypermethylation (CIHM) of tumor‐suppressor genes. Although the CIHM of these genes occurs in non‐neoplastic gastric cells, it is unclear whether this epigenetic alteration is linked with aging and/or gastric cancer risk. We investigated this linkage in noncancerous gastric mucosa infected with H. pylori. Subjects and methods: Noncancerous corpus mucosa was endoscopically obtained from H. pylori‐positive gastric cancer patients (n = 34), and age‐matched H. pylori‐positive noncancerous controls (n = 68). Genomic DNA retrieved from the mucosa was subjected to methylation‐specific polymerase chain reaction for p16, Ecad, and DAPK genes. Linkage between CIHM and clinicopathologic factors was evaluated. Results: CIHM rates of DAPK, Ecad, and p16 promoters were significantly higher in noncancerous gastric mucosa of gastric cancer patients (91, 88, and 68%, respectively) than in noncancerous controls (71, 53, and 25%, respectively). Multivariate regression analysis showed a significant linkage between CIHM in noncancerous mucosa and coexistence of gastric cancer. Significant linkage between polymorphoneutrophil infiltration and CIHM was observed except for CIHM of p16. No linkage was observed between CIHM and other parameters, including age. High CIHM status (all three tested genes methylated) was associated with an increased risk of gastric cancer, with an odds ratio of 9.8 (95% confidence interval, 3.8–25.3). Conclusions: In a subset of the H. pylori‐infected population, CIHM of tumor‐suppressor genes in noncancerous gastric mucosa is linked with the risk of gastric cancer and polymorphoneutrophil infiltration, but not aging. CIHM is a potential marker of gastric cancer risk.