Evaluation of polygenic risk score for risk prediction of gastric cancer.

Genetic variations are associated with individual susceptibility to gastric cancer. Recently, polygenic risk score (PRS) models have been established based on genetic variants to predict the risk of gastric cancer. To assess the accuracy of current PRS models in the risk prediction, a systematic review was conducted. A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models. The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823. Incorporation of epidemiological factors or Helicobacter pylori (H. pylori) status increased the accuracy for risk prediction, while selection of single nucleotide polymorphism (SNP) and number of SNPs appeared to have little impact on the model performance. To further improve the accuracy of PRS models for risk prediction of gastric cancer, we summarized the association between gastric cancer risk and H. pylori genomic variations, cancer associated bacteria members in the gastric microbiome, discussed the potentials for performance improvement of PRS models with these microbial factors. Future studies on comprehensive PRS models established with human SNPs, epidemiological factors and microbial factors are indicated.

Prediction of gastric cancer risk by a polygenic risk score of Helicobacter pylori.

BACKGROUND: Genetic variants of Helicobacter pylori (H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms (SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear. AIM: To assess the performance of a polygenic risk score (PRS) based on H. pylori SNPs in predicting the risk of gastric cancer. METHODS: A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest (RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined. RESULTS: Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio (OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76 (95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve (AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hpEurope strains, with an AUC value of 0.78. CONCLUSION: The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.

Overgrowth of Lactobacillus in gastric cancer.

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.

Cytotoxic xanthones from the plant endophytic fungus Paecilamyces sp. TE-540.

One new xanthone, chryxanthone C (1), together with four known analogues (2-5), were isolated from the cultures of Paecilamyces sp. TE-540, an endophytic fungus obtained from the leaves of Nicotiana tabacum L. The structure of 1 was elucidated by comprehensive spectral analysis including HRESIMS and 1D/2D NMR, which were confirmed by Cu Kα X-ray crystallography. Compound 1 featured an unusual dihydropyran ring fused to an aromatic ring, rather than the commonly occurring prenyl moiety. The cytotoxicity of compounds 1-5 were evaluated against five human tumour cell lines and 4 exhibited moderate to strong cytotoxicities with IC50 values ranging from 5.6 to 14.2 µM.

Apolipoprotein A5 gene polymorphisms are associated with non-alcoholic fatty liver disease.

BACKGROUND: Several studies have reported that apolipoprotein A5 (APOA5) is involved in the development of non-alcoholic fatty liver disease (NAFLD). However, no research has been performed regarding the association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore the association between APOA5 gene polymorphisms and NAFLD in a Chinese Han population. METHODS: Genotypes of the SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 in 232 NAFLD patients and 188 healthy controls were determined using polymerase chain reaction (PCR) analysis. Clinical characteristics were measured using biochemical methods. RESULTS: The five single nucleotide polymorphisms (SNPs) (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 showed no significant association with NAFLD (P > 0.05). The rs10750097 with G allele showed a higher serum level of alkaline phosphatase (ALP) compared with C allele in overall series and NAFLD patients (P < 0.05). The rs1263173(A/A) carriers showed a higher level of glucose compared to the non-carriers in overall series (P < 0.05). The rs17120035(T/T) carriers showed a lower plasma TG level in overall series and NAFLD patients (P < 0.05), and the rs662799(G/G) carriers showed higher levels of plasma triglyceride (TG), ALP, and lower level of high-density lipoprotein (HDL) compared to non-carriers in NAFLD patients (P < 0.05). No significant difference were observed on the clinic parameters of APOA5 rs3135507(T/T) carriers in both group of overall series and NAFLD patients (P > 0.05). CONCLUSIONS: The five SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 gene are not associated with the risk of NAFLD in the Chinese Han population. The genotypes of rs10750097(G/G), rs1263173(A/A), rs17120035(T/T), and rs662799(G/G) performed a significant effect on clinic characteristics in overall series and NAFLD patients, indicating that these polymorphisms may be associated with NAFLD.

Redox-sensitive nanoparticles based on 4-aminothiophenol-carboxymethyl inulin conjugate for budesonide delivery in inflammatory bowel diseases.

The purpose of this study was to develop an oral nanocarrier as budesonide delivery system and to evaluate its therapeutic potential for inflammatory bowel disease (IBD). The nanoparticles (NPs) based on an amphiphilic inulin polymer with 4-aminothiophenol (ATP) grafted onto carboxymethyl inulin (CMI) were prepared. The particle sizes were about 210.18 nm and had the obvious pH/redox sensitive swelling transitions. The drug-release study of NPs <-- >in vitro showed a low release rate (about 45 wt%) in GSH-free media, whereas high release rate (about 80 wt%) in the media containing 20 mM GSH, exhibiting a redox-responsive property. Further in vivo experiments found the NPs tended to accumulate in inflamed sites, and exerted excellent therapeutic efficacy in comparison to drug suspension in colitis mice model. All the results demonstrated that the redox-sensitive NPs, based on amphiphilic inulin, may be used as colon-targeted drug delivery for the treatment of IBD.

Development of novel pH-sensitive thiolated chitosan/PMLA nanoparticles for amoxicillin delivery to treat Helicobacter pylori.

The cysteine conjugated chitosan/PMLA multifunctional nanoparticles were synthesized as targeted Nano-drug delivery system to eradicate Helicobacter pylori. Helicobacter pylori specifically express urea transport protein on its membrane to carrying urea to the cytoplasm urease to supply ammonia that protects bacteria in the acid environment of the stomach. The clinical suitability of topical antimicrobial agents is required to get rid of Helicobacter pylori inside the inflamed basal region. In this work, cysteine conjugated chitosan derivative, Cys-CS for their mucoadhesive and anticoagulant properties was designed and synthesized, for the preparation of multifunctional nanoparticles. The technique turned into optimized to prepare Cys-CS/PMLA nanoparticles for encapsulation of amoxicillin. The results showed that amoxicillin-Cys-CS/PMLA nanoparticles exhibit favorable pH-sensitive properties that could procrastinate the release of amoxicillin at gastric acid and allow the drug to deliver and target to Helicobacter pylori at its survival region efficiently. In comparison with unmodified amoxicillin-chitosan/PMLA nanoparticles, effective inhibition of Helicobacter pylori growth was observed for amoxicillin-Cys-CS/PMLA nanoparticles. These results indicate that the multifunctional amoxicillin-loaded nanoparticles have great potential for the effective treatment of Helicobacter pylori infection. They can also be used as pharmacologically powerful nanocarriers for oral targeted delivery of different therapeutic drugs to treat Helicobacter pylori.

Association between Helicobacter pylori infection and angiographically demonstrated coronary artery disease: A meta-analysis.

Coronary artery disease (CAD) is a leading cause of mortality globally. However, the etiology and pathogenesis of CAD are not fully understood. The aim of the present meta-analysis was to estimate the association between the risk of CAD and Helicobacter pylori (H. pylori) infection. A literature search was performed to identify eligible studies published prior to August 14, 2014. Fixed or random effect meta-analytical methods were used to pool the data and perform the subgroup analyses. The effect measures estimated were the odds ratios (OR) for dichotomous data reported with 95% confidence intervals (95% CI). Of the 109 studies identified using the search parameters, 26 cross-sectional studies were eligible involving 3,901 CAD patients and 2,751 controls. H. pylori infection was associated with an increased risk of CAD (OR: 1.96, 95% CI: 1.47-2.63, P<0.00001). When the adjusted ORs were used to conduct another meta-analysis, the OR value decreased, but the association remained significant (OR: 1.42, 95% CI: 1.09-1.86, P=0.008). The association between H. pylori infection and CAD risk was stronger in younger individuals than in older individuals (OR: 2.36, 95% CI 1.50-3.73 vs. OR: 1.59, 95% CI: 1.19-2.11). A significant association was observed in studies from Europe (OR: 2.11, 95% CI: 1.54-2.88, P=0.01) and the USA (OR: 1.43, 95% CI: 1.08-1.91, P=0.36). There is a potential association between H. pylori infection and the risk of CAD. The association may be influenced by age and ethnicity.

Association of Adiponectin Gene Polymorphisms With the Risk of Coronary Artery Disease in Patients With Nonalcoholic Fatty Liver Disease in a Chinese Han Population.

BACKGROUND: Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. OBJECTIVES: The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. MATERIALS AND METHODS: In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. RESULTS: There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0.042, respectively) than those of their noncarrier counterparts. CONCLUSIONS: In this Northern Chinese Han population, the Adrs266729 and rs2241766 G alleles were closely associated with the occurrence of NAFLD. However, only NAFLD patients who carried the Adrs266729 G allele had an increased risk of developing CAD.

Reduced genome size of Helicobacter pylori originating from East Asia.

Helicobacter pylori (H. pylori), a major pathogen colonizing the human stomach, shows great genetic variation. Comparative analysis of strains from different H. pylori populations revealed that the genome size of strains from East Asia decreased to 1.60 Mbp, which is significantly smaller than that from Europe or Africa. In parallel with the genome reduction, the number of protein coding genes was decreased, and the guanine-cytosine content was lowered to 38.9%. Elimination of non-essential genes by mutations is likely to be a major cause of the genome reduction. Bacteria with a small genome cost less energy. Thus, H. pylori strains from East Asia may have proliferation and growth advantages over those from Western countries. This could result in enhanced capacity of bacterial spreading. Therefore, the reduced genome size potentially contributes to the high prevalence of H. pylori in East Asia.

Participation of microbiota in the development of gastric cancer.

There are a large number of bacteria inhabiting the human body, which provide benefits for the health. Alterations of microbiota participate in the pathogenesis of diseases. The gastric microbiota consists of bacteria from seven to eleven phyla, predominantly Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. Intrusion by Helicobacter pylori (H. pylori) does not remarkably interrupt the composition and structure of the gastric microbiota. Absence of bacterial commensal from the stomach delays the onset of H. pylori-induced gastric cancer, while presence of artificial microbiota accelerates the carcinogenesis. Altered gastric microbiota may increase the production of N-nitroso compounds, promoting the development of gastric cancer. Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.

[Polymorphism rs738409 in PNPLA3 is associated with inherited susceptibility to non-alcoholic fatty liver disease].

OBJECTIVE: To study the relationship between the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hereditary susceptibility to non-alcoholic fatty liver disease (NAFLD) by detecting single nucleotide polymorphisms (SNPs). METHODS: Peripheral blood DNA from 315 patients diagnosed with NAFLD (including the spectrum of simple steatosis (SS) and non-alcoholic steatosis (NASH)) and 336 control subjects was used to determine the PNPLA3 genotype by polymerase chain reaction (PCR) and direct sequencing. The relationship of SNPs and NAFLD-related markers of liver function were assessed by correlation analysis. RESULTS: The SNP rs738409 was identified in more of the NAFLD patients (allele variant frequencies: NAFLD, 65.40%; NASH: 71.87%; SS, 56.47%) than in the controls (33.18%). Case-control analysis revealed that carriers of the 148GG genotype were at 3.81-fold (95% CI: 3.03 ~ 4.79) higher risk of developing NAFLD and at 1.97-fold (95% CI: 1.41 ~ 2.75) higher risk of progressing from SS to NASH, compared with non-carriers. rs738409 was also found to be associated with serum levels of alanine aminotransferase (ALT) and y-glutamyltransferase (y-GT) (both P less than 0.05). Carriers of the 148GG genotype had significantly higher body mass index, ALT, and fasting insulin than carriers of the 148CC genotype (all P less than 0.05), and significantly higher level of serum HDL than carriers of either the 148CC genotype or the 148GC genotype (both P less than 0.05). CONCLUSION: Polymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD in the Chinese population. The rs738409 polymorphism, in particular, is related to development and progression of NAFLD and may play a role in the contribution of PNPLA3 to NAFLD pathogenesis.

Relatedness of Helicobacter pylori populations to gastric carcinogenesis.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and possibly result from geographical separation of the bacterium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different populations of H. pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H. pylori. Further studies are indicated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.

[HBV genotypes distribution and YMDD spontaneous mutation in Qingdao population].

OBJECTIVE: To investigate the distribution of hepatitis B virus (HBV) genotypes in Qingdao, and the relationship of HBV genotypes with the serum HBV-DNA levels and HBV YMDD spontaneous mutation of patients, then to discuss the clinical significance. METHODS: Hepatitis B virus genotypes and YMDD spontaneous mutation of 144 patients were detected by real time PCR (Taqman probe), then the results were analyzed by statistical method. RESULTS: Of the 144 patients, 130 (90.3%) were genotype C, 12 (8.3%) were genotype B, and 2 (1.4%) were neither genotype B nor genotype C; 33 (22.9%) were detected to have YMDD mutation, and 25 (75.5%) were YVDD positive, 3 (9.1%) were YIDD positive, 5 (15.2%) were YVDD and YIDD positive. There were no significant differences between clinical diagnosis, serum HBV-DNA levels, YMDD spontaneous mutation and HBV genotypes (P > 0.05). CONCLUSION: Genotype C is the dominant position for HBV genotype in Qingdao. Untreated patients with chronic hepatitis B have YMDD spontaneous mutation. HBV genotypes have no association with YMDD spontaneous mutation and the development of diseases.

Specific HLA-DQB1 alleles associated with risk for development of hepatocellular carcinoma: a meta-analysis.

AIM: To evaluate the association of human leukocyte antigen (HLA)-DQB1 alleles with hepatocellular carcinoma (HCC) through meta-analysis of published data. METHODS: Case-control studies on HLA-DQB1 allele association with HCC published up to January 2010 were included in the analyses. The odds ratios (ORs) of HLA-DQB1 allele distributions in HCC patients were analyzed and compared with healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. A meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. Seven case-control studies containing 398 cases and 594 controls were included in the final analysis. RESULTS: Among the five family alleles, two (DQB1*02 and DQB1*03) were found to be significantly associated with the risk of HCC. The combined OR for the association of DQB1*02 and DQB1*03 allele with the risk for HCC was 1.78 (95% CI: 1.05-3.03, P = 0.03) and 0.65 (95% CI: 0.48-0.89, P = 0.007), respectively. Among the 13 specific alleles, two (DQB1*0502 and DQB1*0602) were significantly associated with risk of HCC. The combined OR for the association of DQB1*0502 and DQB1*0602 allele with the risk for HCC was 1.82 (95% CI: 1.14-2.92, P = 0.01) and 0.58 (95% CI: 0.36-0.95, P = 0.03), respectively. No significant association was established for other HLA-DQB1 family alleles and specific alleles. CONCLUSION: Our results support the hypothesis that specific HLA-DQB1 allele families and alleles might influence the susceptibility or resistance to HCC, although it needs further investigations.

Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis.

UNLABELLED: The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to update the 2007 meta-analysis to systematically assess the accuracy of APRI in predicting significant fibrosis, severe fibrosis, and cirrhosis stage in hepatitis C virus (HCV) monoinfected and HCV / human immunodeficiency virus (HIV) coinfected individuals. Studies comparing APRI versus biopsy in HCV patients were identified via a thorough literature search. Areas under summary receiver operating characteristic curves (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to examine the APRI accuracy for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis. Heterogeneity was explored using meta-regression. Twenty-one additional studies were eligible for the update and, in total, 40 studies were included in this review (n = 8,739). The summary AUROC of the APRI for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis were 0.77, 0.80, and 0.83, respectively. For significant fibrosis, an APRI threshold of 0.7 was 77% sensitive and 72% specific. For severe fibrosis, a threshold of 1.0 was 61% sensitive and 64% specific. For cirrhosis, a threshold of 1.0 was 76% sensitive and 72% specific. Moreover, we found that the APRI was less accurate for the identification of significant fibrosis, severe fibrosis, and cirrhosis in HIV/HCV coinfected patients. CONCLUSION: Our large meta-analysis suggests that APRI can identify hepatitis C-related fibrosis with a moderate degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among chronic hepatitis C patients.

Association between HLA-DRB1 alleles polymorphism and hepatocellular carcinoma: a meta-analysis.

BACKGROUND: HLA-DRB1 allele polymorphisms have been reported to be associated with hepatocellular carcinoma susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to explore whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer susceptibility to hepatocellular carcinoma. METHODS: Case-control studies on HLA-DRB1 alleles association with HCC were searched up to January 2010 through a systematic review of the literature. The odds ratios (ORs) of HLA-DRB1 allele distributions in patients with hepatocellular carcinoma were analyzed against healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. RESULTS: Eight case-control studies were included in the final analysis. Among the 3 HLA-DRB1 alleles studied, DRB1*07 and DRB1*12 were significantly associated with the risk of HCC in the whole populations (OR = 1.65, 95% CI: 1.08-2.51, P = 0.02 and OR = 1.59, 95% CI: 1.09-2.32, P = 0.02, respectively). No significant association was established for DRB1*15 allele with HCC in the whole populations. Subgroup analysis by ethnicity showed that DRB1*07, DRB1*12 and DRB1*15 alleles significantly increased the risk of hepatocellular carcinoma in Asians (OR = 2.10, 95% CI: 1.06-4.14, P = 0.03; OR = 1.73, 95% CI: 1.17-2.57, P = 0.006 and OR = 2.88, 95%CI: 1.77-4.69, P <0.001, respectively). CONCLUSION: These results support the hypothesis that specific HLA-DRB1 alleles might influence the susceptibility of hepatocellular carcinoma. Large, multi-ethnic confirmatory and well designed studies are needed to determine the host genetic determinants of hepatocellular carcinoma.

Comparative genomics of Helicobacter pylori.

Genomic sequences have been determined for a number of strains of Helicobacter pylori (H. pylori) and related bacteria. With the development of microarray analysis and the wide use of subtractive hybridization techniques, comparative studies have been carried out with respect to the interstrain differences between H. pylori and inter-species differences in the genome of related bacteria. It was found that the core genome of H. pylori constitutes 1111 genes that are determinants of the species properties. A great pool of auxillary genes are mainly from the categories of cag pathogenicity islands, outer membrane proteins, restriction-modification system and hypothetical proteins of unknown function. Persistence of H. pylori in the human stomach leads to the diversification of the genome. Comparative genomics suggest that a host jump has occurs from humans to felines. Candidate genes specific for the development of the gastric diseases were identified. With the aid of proteomics, population genetics and other molecular methods, future comparative genomic studies would dramatically promote our understanding of the evolution, pathogenesis and microbiology of H. pylori.

Association between the presence of H pylori in the liver and hepatocellular carcinoma: a meta-analysis.

AIM: To evaluate the arguments for and against the possible roles of H pylori in hepatocellular carcinoma (HCC). METHODS: We performed a systematic review of all relevant studies published in the literature. A total of 103 clinical trials and reports were identified, but only 10 trials qualified under our selection criteria. A meta-analysis was carried out by a biostatistician according to the Cochrane Reviewers' Handbook recommended by The Cochrane Collaboration. RESULTS: Nine case-control studies and one retrospective cross sectional study were included in the final analysis. Overall the prevalence of H pylori infection was 53.3% (129 of 242) in cases and 10.4% (29 of 280) in controls, and the summary odds ratio for the association of H pylori infection with the risk for HCC (using the fixed-effects model, which accounted for the homogeneity across the 10 studies) was determined to be 13.63 (95% CI, 7.90-23.49). CONCLUSION: Our analysis showed a positive association between H pylori infection and the risk of HCC, with an indication of possible publication bias and possible confounders due to study designs that showed results of less pronounced associations.

Effect of Helicobacter pylori infection on gastric epithelial proliferation in progression from normal mucosa to gastriccarcinoma.

AIM:To study the effect of Helicobacter pylori (H. pylori) infection on gastric epithelial proliferation in the progression from normal mucosa to gastric carcinoma.METHODS:Gastric biopsy specimens from normal controls (n = 11), superficial gastritis (n = 32), atrophic gastritis with intestinal metaplasia (n= 83), dysplasia (n= 25) and gastric carcinoma (n = 10) were studied by immunohistochemical stianing of proliferating cell nuclear antigen (PCNA).RESULTS: The gastric epithelial proliferation, expressed as PCNA labeling index (LI)%, was progressively increased in successive stages from normal mucosa to gastric carcinoma regardless of H. pylori status. There was significant difference in PCNA LI% among all groups (P <0.01). The analysis pursuing the effect of H. pylori infection on gastric epithelial proliferation in the progression from normal mucosa to gastriccarcinoma showed that in superficial gastritis and mild atrophic gastritis groups, PCNA LI% in H. pylori positive patients were 13.14 ± 1.6 and 19.68 ± 2.22 respectively, significantly higher than 6.95 ± 0.78 and 11.34 ± 1.89 in H. pylori negative patients (P <0.01); but there was no such difference in other groups (P >0.05).CONCLUSION:H. pylori infection causes increased gastric epithelial proliferation in the stages of superficial and mild atrophic gastritis and may play a part in triggering gastric carcinogenesis.