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.

乳杆菌抑制幽门螺杆菌感染的分子机制

乳杆菌具有调节胃肠道菌群、改善胃肠道功能的益生作用。幽门螺杆菌是定植于胃黏膜的革兰阴性致病菌,可诱发胃癌。目前,幽门螺杆菌根除率逐年下降,临床上开始尝试应用嗜酸乳杆菌、鼠李糖乳杆菌和加氏乳杆菌等乳杆菌联合抗生素治疗幽门螺杆菌。然而不同临床研究结论有差异,临床疗效仍有待提升。该文通过综述乳杆菌治疗幽门螺杆菌的临床研究,进一步探讨其抑制幽门螺杆菌感染的分子机制,包括细菌素的直接杀菌、黏附抑制、胃肠道微生物群调节、炎症抑制等,为筛选理想乳杆菌菌株,提高幽门螺杆菌临床疗效提供新方案。

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 metaanalysis 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 F1 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.

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 guaninecytosine 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.

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 HLADQB1 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.

Relatedness of Helicobacter pylori populations to gastric carcinogenesis

Helicobacter pylori （H. pylorl） is a Gram-negative bac- terium 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 hpAfrical, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and pos- sibly result from geographical separation of the bac- terium 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 popula- tions 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 indi- cated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.

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.

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.

Apolipoprotein A5 gene polymorphisms are associated withnon-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 regardingthe association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore theassociation between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.

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 hp Europe 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.

The Pathogenesis of Acute on Chronic Hepatitis B liver Failure

Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would benefit for the prognosis and raise the survival rate of patients.

The Correlation between Gene Polymorphism and Hepatocellular Carcinoma

The association of gene polymorphism and susceptibility to hepatocellular carcinoma(HCC)has been widely studied in recent years.Gene mutations are closely related to HCC.Understanding and measuring the gene mutations are useful to reduce the incidence of HCC and improve its prognosis.

Helicobacter Infection and Chronic Liver Diseases

This paper reviews the recent Helicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.