Lower Risk Of Gastric Cancer Research Articles

Dietary patterns and gastric cancer risk in a Korean population: a case-control study.

Dietary pattern analysis has been considered as an approach to capture the complex interactions of overall diet, which are often lost in studies of single dietary components (e.g., foods and nutrients). The aim of this study was to identify the major dietary patterns of Koreans via principal component analysis based on the food groups and to investigate the association between dietary patterns and gastric cancer (GC) risk. In this study, participants were recruited from the National Cancer Center, Korea. Among them, 415 cases were diagnosed with early GC, and 830 controls were age- and sex-matched at a ratio of 1:2. To determine the subjects' dietary patterns, 34 predefined food groups based on the 106-item semiquantitative food frequency questionnaire (SQFFQ) were used. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated across the tertiles of dietary pattern scores using logistic regression models. The two dietary patterns derived in this study were named westernized and prudent. Those patterns explained 24.83% of the total variation in food intake. Higher scores on the prudent pattern was inversely associated with the risk of GC (OR [95% CI] for the highest vs. lowest tertiles: 0.58 [0.41-0.84], p for trend = 0.004). Our findings suggest that adherence to the prudent dietary pattern represented by high loadings of vegetables and fruits, was associated with lower GC risk. Further studies with a prospective design and larger sample sizes are necessary.

A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk.

We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.

Statins Were Associated with a Reduced Gastric Cancer Risk in Patients with Eradicated Helicobacter Pylori Infection: A Territory-Wide Propensity Score Matched Study.

Individuals may still develop gastric cancer even after Helicobacter pylori eradication. We aimed to investigate statin effect on gastric cancer development in H. pylori-eradicated subjects. All adult subjects who were prescribed clarithromycin-based triple therapy between 2003 and 2012 were identified in this retrospective cohort study utilizing a territory-wide electronic healthcare database. Patients were observed from index date of H. pylori therapy, and censored at gastric cancer diagnosis, death, or December 2015 (study end date). Statin use was defined as ≥180-day use after index date. Exclusion criteria included gastric cancer diagnosed within the first year after index date, previous gastric cancer or gastrectomy, and H. pylori treatment failure. Subdistribution hazard ratio (SHR) of gastric cancer with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities, and other drug usage, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin). During a median follow-up of 7.6 years (interquartile range = 5.1-10.3), 169 (0.27%) of 63,605 patients developed gastric cancer at an incidence rate of 3.5 per 10,000 person-years. Among 22,870 PS-matched subjects, statins were associated with a lower gastric cancer risk (SHR = 0.34; 95% confidence interval, 0.19-0.61), in a duration- and dose-response manner (P trend < 0.05). Statins were associated with a lower gastric cancer risk in a duration- and dose-response manner among H. pylori-eradicated patients. This study provides evidence on the additional benefits of statins as chemopreventive agents against gastric cancer among H. pylori-eradicated patients.

Highlights of This Issue

Mapping breast cancer survival can help cancer-control programs prioritize efforts with limited resources. Wiese and colleagues used Bayesian spatial models to assess whether geographic variation in breast cancer survival among patients in New Jersey persists after adjusting for key individual and neighborhood measures of poverty and economic inequality. The results support a growing understanding of the independent association between neighborhood socioeconomic measures and breast cancer survival. More effective health interventions could be developed if geographic variations were examined more routinely in the context of neighborhood socioeconomic inequalities in addition to individual characteristics.The impact of processed meat intake on the risk of bladder cancer is not clear. In this study, Xu evaluated the association of processed meat intake with bladder cancer using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. As a result, intake of processed red meat was significantly associated with the incidence of bladder cancer after multivariate adjustment. By contrast, there was only a suggestive but not significant association between total processed meat intake and bladder cancer risk. The study suggests that bladder cancer risk is increased with cumulative intake of processed red meat.Infection with Helicobacter pylori can lead to chronic atrophic gastritis, a gastric cancer precursor. Autoimmune gastritis is an alternative form of gastritis that may be marked by autoantibodies against parietal cells (APCA). Wang and colleagues measured seropositivity to APCA in a nested case–control study of upper gastrointestinal cancers in a rural Chinese cohort. The authors found that APCA positivity was associated with lower risk of gastric cancer that was strongest in the gastric cardia. APCA negativity when assessed along with a serologic marker for atrophic gastritis revealed complex and strong associations with gastric cancer that may be useful in risk stratification.Multiple myeloma (MM) is a common hematologic malignancy preceded by monoclonal gammopathy of undetermined significance (MGUS). Chang and colleagues aimed to identify a new clinical predictor to guide MGUS management. Multivariable analyses were performed using data from the U.S. Veterans Health Administration. The rate of rise in serum monoclonal protein concentration of &gt;0.1 g/dL in the year following MGUS diagnosis was positively associated with progression of MGUS to MM. These findings enhance the current risk stratification. The identified clinical predictor is a dynamic measure for disease progression with prognostic value. It has the potential to inform MGUS management and MM prevention.

Association between the relative abundance of gastric microbiota and the risk of gastric cancer: a case-control study

The human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17–2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94–7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42–4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10–0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.

Review: Gastric cancer-Clinical aspects.

Gastric cancer (GC) was responsible for over 1000000 new cases in 2018 and an estimated 783000 deaths, making it still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Divergent trends for GC incidence were observed in the USA. Incidence rates, particularly for non-cardia GC, were stable or increasing among persons aged <50years. In an analysis of data from a public hospital database in Hong Kong, treatment of Helicobacter pylori infection was associated with a lower risk of GC, particularly in older subjects who received treatment ≥10years before. Based on the results of a 16-year endoscopy-based follow-up eradication trial, patients with incomplete-type intestinal metaplasia (IM) should receive endoscopic surveillance upon H. pylori eradication therapy. Updated guidelines on the endoscopic surveillance of preneoplastic conditions of the stomach (MAPS II) have been published. In the RAINFALL trial, the addition of ramucirumab to a backbone chemotherapy as a first-line regimen failed to improve overall survival (OS) of patients with metastatic disease. Also, pembrolizumab did not prolong OS when compared to paclitaxel in the second-line treatment of patients with advanced GC or esophagogastric junction (EGJ) cancer. Trifluridine/tipiracil improved OS by 2.1months in the third or further treatment line of patients with advanced GC. In a systematic investigation conducted on Chinese patients with GC, CLDN18-ARHGAP26/6 fusion was associated with signet-ring cell content and was prognostic for a worse outcome and predictive for no benefit from oxaliplatin/fluoropyrimidine-based chemotherapy. Organoid cultures represent an appealing model that may be applied for therapy response testing in the near future.

Polymorphisms in IL-10 and TGF-\u03b2 gene promoter are associated with lower risk to gastric cancer in a Mexican population

BackgroundHelicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC.MethodsThe study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5′-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models.ResultsBoth genotypes, TC (OR = 0.51, 95% CI = 0.27–0.98) and TT (OR = 0.42, 95% CI = 0.20–0.91) in the locus − 509 of the TGF-β promoter were significantly associated with GC. The TT genotype in the locus − 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17–0.81). No significant association was found with SNPs IL-4 –590 T/C (rs1800629), IL-6 –573G/C (rs1800796), IL-10 –592C/A (rs1800872), IL-10 –1082A/G (rs1800896), and, IFN-γ –1615C/T (rs2069705).ConclusionsSNPs in TGFβ (− 509 C/T, rs1800469) and IL-10 (− 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.

Flavonoids and the Risk of Gastric Cancer: An Exploratory Case-Control Study in the MCC-Spain Study.

Several epidemiological studies have investigated the association between the dietary flavonoid intake and gastric cancer (GC) risk; however, the results remain inconclusive. Investigating the relationship between the different classes of flavonoids and the histological types and origin of GC can be of interest to the research community. We used data from a population-based multi-case control study (MCC-Spain) obtained from 12 different regions of Spain. 2700 controls and 329 GC cases were included in this study. Odds ratios (ORs) were calculated using the mixed effects logistic regression considering quartiles of flavonoid intakes and log2. Flavonoid intake was associated with a lower GC risk (ORlog2 = 0.76; 95% CI = 0.65–0.89; ORq4vsq1 = 0.60; 95%CI = 0.40–0.89; ptrend = 0.007). Inverse and statistically significant associations were observed with anthocyanidins, chalcones, dihydroflavonols and flavan-3-ols. The isoflavanoid intake was positively associated with higher cancer risk, but without reaching a statistical significance. In general, no differences were observed in the GC risk according to the location and histological type. The flavonoid intake seems to be a protective factor against GC within the MCC-study. This effect may vary depending on the flavonoid class but not by the histological type and location of the tumor. Broader studies with larger sample size and greater geographical variability are necessary.

Association Between Nitrite and Nitrate Intake and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis.

BackgroundStudies have shown inconsistent associations of nitrite and nitrate intake with the risk of gastric cancer or its associated mortality. We performed a meta-analysis of observational studies to evaluate the correlation of nitrite and nitrate intake with the risk of gastric cancer.Material/MethodsWe searched for studies reporting effect estimates and 95% confidence intervals (CIs) of gastric cancer in PubMed, EMBASE, and the Cochrane Library through November 2018. The summary results of the included studies were pooled using a random-effects model.ResultsEighteen case-control and 6 prospective cohort studies recruiting 800 321 participants were included in this study. The summary results indicated that the highest (odds ratio [OR], 1.27; 95%CI, 1.03–1.55; P=0.022) or moderate (OR: 1.12; 95%CI, 1.01–1.26; P=0.037) nitrite intake were associated with a higher risk of gastric cancer. However, we noted that high (OR, 0.81; 95%CI, 0.68–0.97; P=0.021) or moderate (OR, 0.86; 95%CI, 0.75–0.99; P=0.036) nitrate intakes were associated with a reduced risk of gastric cancer. These associations differed when stratified by publication year, study design, country, the percentage of male participants, assessment of exposure, adjusted model, and study quality.ConclusionsHigh or moderate nitrite intake was associated with higher risk of gastric cancer, whereas high or moderate nitrate intake was correlated with lower risk of gastric cancer.

Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer.

BACKGROUNDThe lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited.AIMTo investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population.METHODSA total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed.RESULTSAll the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3’-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters.CONCLUSIONThe let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.

Berberine Attenuated Proliferation, Invasion and Migration by Targeting the AMPK/HNF4α/WNT5A Pathway in Gastric Carcinoma.

Background: Recent epidemiologic studies have found that patients with diabetes have a higher risk of gastric cancer (GC), and the long-term use of metformin is associated with a lower risk of gastric cancer. It is believed that blocking tumor energy metabolic alterations is now emerging as a new therapeutic approach of cancer. Berberine, a natural isoquinoline alkaloid, could modulate lipid metabolism and glucose homeostasis by regulating the expression of HNF4α in many metabolic diseases. Here, we investigated the effect of Berberine on GC and its possible molecular mechanism through targeting HNF4α.Methods and Results: (1) AGS and SGC7901 gastric cancer cells were treated with Berberine (BBR). We found that in AGS and SGC7901 cell, BBR inhibited cell proliferation in a time- and dose-dependent manner through downregulating C-myc. BBR also induced G0-G1 phase arrest with the decreased expression of cyclin D1. Moreover, BBR attenuated the migration and invasion by downregulating MMP-3. (2) The lentivirus infection was used to silence the expression of HNF4α in SGC7901 cell. The results demonstrated that the knockdown of HNF4α in SGC7901 slowed cells proliferation, induced S phase arrest and dramatically attenuated gastric cancer cells’ metastasis and invasion. (3) We performed GC cells perturbation experiments through BI6015 (an HNF4α antagonist), AICAR (an AMPK activator), Compound C (AMPK-kinase inhibitor), metformin and BBR. Our findings indicated that BBR downregulated HNF4α while upregulating p-AMPK. Moreover, the inhibition of HNF4α by BBR was AMPK dependent. (4) Then the LV-HNF4α-RNAi SGC7901 cell model was used to detect the downstream of HNF4α in vitro. The results showed that the knockdown of HNF4α significantly decreased WNT5A and cytoplasmic β-catenin, but increased E-cadherin in vitro. Berberine also downregulated WNT5A and cytoplasmic β-catenin, the same as LV-HNF4α-RNAi and BI6015 in GC cells. (5) Finally, the SGC7901 and LV-HNF4α-RNAi SGC7901 mouse-xenograft model to evaluate the effect of BBR and HNF4α gene on GC tumor growth. The result illustrated that BBR and knockdown of HNF4α suppressed tumor growth in vivo, and BBR decreased HNF4α, WNT5A and cytoplasmic β-catenin levels, the same effect as HNF4α knockout in vivo.Conclusion: BBR not only had proliferation inhibition effect, attenuated the invasion and migration on GC cell lines, but also suppressed the GC tumor growth in vivo. The anti-gastric cancer mechanism of BBR might be involved in AMPK-HNF4α-WNT5A signaling pathway. HNF4α antagonists, such as BBR, could be a promising anti-gastric cancer treatment supplement.

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication.

Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level.

Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer Susceptibility in a Korean Population

PurposeHalf of the world’s gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. Materials and MethodsWe performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. ResultsWe showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer.ConclusionOur result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.

Effects of Helicobacter pylori Treatment on Incidence of Gastric Cancer in Older Individuals

Although eradication of Helicobacter pylori infection reduces the risk of gastric cancer, few data are available on its effects in older subjects. We compared the age-specific risk of gastric cancer in a large cohort of subjects who received H pylori eradication therapy vs a matched general population. We searched the Hospital Authority database of Hong Kong to identify individuals with H pylori infection who had received a course of clarithromycin-containing eradication therapy from January 2003 through December 2012. We compared the gastric cancer incidence in this cohort with the expected incidence for the local general population by retrieving the gastric cancer incidence of the age- and sex-matched population from 2003 through 2014 (the latest available year) from the Hong Kong Cancer Registry. The primary outcome was the incidence of gastric cancer development in the cohort treated for Hpylori infection vs the expected number of gastric cancer cases in the general population. Analyses were conducted by a priori age groups of less than 40 years, 40-59 years, and 60 years or older. Among 73,237 subjects infected with H pylori who received eradication therapy, 200 (0.27%) developed gastric cancer during a median follow-up time of 7.6 years. Compared with the matched general population, the gastric cancer risk was significantly lower in subjects 60 years or older who had received H pylori treatment (standardized incidence ratio [SIR], 0.82; 95% confidence interval [CI], 0.69-0.97; P= .02) but not in younger groups. When data were stratified based on time from H pylori treatment (less than 5 years, 5-9 years, and 10 or more years), the risk of gastric cancer was significantly lower than the general population 10 or more years after eradication in the group 40-59 years old (SIR 0.32; 95% CI, 0.08-0.88; P= .04) and the group 60years or older (SIR, 0.42; 95% CI, 0.42-0.84; P= .02) than the other age groups. In an analysis of data from a public hospital database on Hong Kong, we associated treatment of H pylori infection with a lower risk of gastric cancer, particularly in older subjects, 10 or more years after treatment.

Functional long non-coding RNAs associated with gastric cancer susceptibility and evaluation of the epidemiological efficacy in a central Chinese population

AimTo screen and validate the gastric cancer-associated long non-coding RNAs (lncRNAs) and their functional single nucleotide polymorphisms (SNPs). MethodsBased on case-control design, we select the differentially expressed lncRNAs by bioinformation tools and validate SNPs in lncRNAs genes in population. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the effect of epidemiology. ResultsFour lncRNAs with SNPs (lnc-EVX1-3:3 (rs1859168), lnc-MACC1-1:7 (rs3815254), lnc-AMFR-1:1 (rs4784659) and lnc-ZNF33B-2:1 (rs579501)) were selected to be validated in population. The unconditional multiple logistic regression based on the dominant (odds ratio, OR=0.64, 95%confidence interval, 95%CI: 0.47–0.86) and recessive genetic model (OR=1.77, 95%CI: 1.34–2.35) showed rs1859168 was significantly associated with lower risk of gastric cancer. The dominant (OR=0.42, 95%CI:0.31–0.57) and additive (OR=0.52, 95%CI:0.40–0.67) genetic model revealed that rs4784659 decreased the risk of gastric cancer. Similarly, the dominant (OR=0.72, 95%CI: 0.52–0.98) and additive (OR=0.73, 95%CI: 0.56–0.97) genetic model showed the individuals with rs579501 had reduced risk of gastric cancer. Whereas no statistical association between rs3815254 and gastric cancer. ARP and PARP for gastric cancer associated with rs1859168 in dominant model (56.25%, 33.05%), and in recessive model (43.50% and 29.37%). For rs4784659, ARP and PARP were 138.09% and 10.39% in dominant model, 92.31% and 8.76% in additive model. For rs579501, ARP and PARP were 38.89% and 4.03% in dominant model, 36.99% and 3.88% in additive model. ConclusionOur findings showed rs4784659, rs579501 and rs1859168 reduced the susceptibility of gastric cancer. From epidemiological perspective, the lncRNAs with SNPs attenuate the development of gastric cancer.

Association between alcohol consumption and the risk of gastric cancer: a meta-analysis of prospective cohort studies.

Alcohol consumption is inconsistently associated with the risk of gastric cancer morbidity and mortality. The aim of this study was to systematically evaluate the association between alcohol consumption on gastric cancer risk. The PubMed, Embase, and Cochrane Library databases were searched from inception through April 2017. Prospective cohort studies evaluating the association between alcohol consumption and risk of gastric cancer which report its effect estimates with 95% confidence intervals (CIs) were included. The results summary was performed using the random-effect model. Twenty-two cohort studies involving 22,545 cases of gastric cancer and 5,820,431 participants were identified and included in our data analysis. Overall, drinking had little or no effect on gastric cancer as compared with non-drinkers. Furthermore, light and moderate alcohol consumption had no significant effect on gastric cancer risk when compared with non-drinkers. However, heavy alcohol consumption was associated with a greater risk of gastric cancer when compared with non-drinkers. The findings of the subgroup analyses indicated that light alcohol consumption was associated with a lower risk of gastric cancer in women, while heavy alcohol consumption was associated with an increased risk of gastric cancer regardless of country, gender, whether the study reported gastric cancer incidence, or whether the study adjusted for body mass index, educational attainment, or physical activity. The findings of this study suggest that light alcohol consumption might play a protective effect on gastric cancer in women, while heavy alcohol consumption is associated with a significantly increased risk of gastric cancer in all subgroups.

Two populations of less-virulent Helicobacter pylori genotypes in Bangladesh.

Bangladesh has a population with a low gastric cancer risk but high prevalence of Helicobacter pylori infection. Several studies have examined virulence genes in H. pylori from Bangladesh. We analyzed cagA and vacA subtypes and their association with severe histology phenotypes, and analyzed population types among Bangladeshi strains. We included patients who underwent endoscopy in Dhaka. Sequences of virulence genes and seven housekeeping genes were obtained by next generation sequencing and confirmed by Sanger sequencing. We isolated 56 H. pylori strains from 133 patients, of which 73.2% carried cagA, and all were considered Western-type. Patients infected with cagA-positive strains had more severe histological scores than patients infected with cagA-negative strains. Among vacA s1 and m1 genotypes, the s1a (97.8%, 43/44) and m1c (28/30, 93.3%) genotypes were predominant. All strains containing s1 and m1 (30/56, 53.6%) also had i1, d1, and c1. In contrast, all strains containing the less-virulent genotypes s2 and m2 (12/56, 21.4%) also possessed i2, d2, and c2. Multivariate analysis indicated that subjects infected with vacA m1-genotype strains only had a significantly higher risk of antrum atrophy than patients infected with m2-genotype strains. Of the two main H. pylori populations in this study, hpAsia2 strains were associated with higher activity and inflammation in the antrum compared to hpEurope strains; however, only vacA s1m1i1d1c1 strains, independent of population type, were significantly associated with inflammation in the antrum, unlike the s2m2i2d2c2 genotype. In conclusion, Bangladeshi strains were divided into two main populations of different genotypes. The low incidence of gastric cancer in Bangladesh might be attributable to the high proportion of less-virulent genotypes, which may be a better predictor of gastric cancer risk than the ancestral origin of the H. pylori strains. Finally, the vacA m region may be a better virulence marker than other regions.

Serological Evaluation of Gastric Cancer Risk Based on Pepsinogen and Helicobacter pylori Antibody: Relationship to Endoscopic Findings

Backgrounds and Aims: The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system. Methods: We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated. Results: Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (<3 U/mL) of the Hp-Ab improved the discrimination of group A with CAG by 8%. Conclusion: The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.

Genotyping of Helicobacter pylori shows high diversity of strains circulating in central Vietnam

In Vietnam, the high prevalence of Helicobacter pylori infection represents a serious health problem. Virulence genes of H. pylori have been associated to increased risk of severe gastrointestinal diseases and the genetic background differs in geographical areas. We investigated cagA and vacA genotypes of H. pylori from dyspeptic patients from central Vietnam and the correlation with clinical outcomes; we also performed sequencing analysis of partial cagA gene.Overall, 84% of strains were cagA-positive, 75% were East-Asian type with a prevalence of vacAs1i1m1 and vacAs1i1m2 genotypes (66.7% and 33.3%, respectively) and 9% were Western type vacAs1i1m1 (n=4) and vacAs1i1m2 (n=4); vacAs1i2m2 (n=4) and vacAs2i2m2 (n=2) genotypes were associated to cagA-negative. Strains from gastric ulcer and cancer were of East-Asian type, while cagA-negative or Western strains were from gastritis and duodenal ulcer. H. pylori strains from gastric ulcer patients were predominantly vacAs1i1m1 compared to other vacA genotypes (p<0.05). East-Asian type strains vacAs1i1m1 or vacAs1i1m2 were found in gastric cancer patients and also in less severe disease. Phylogenetic tree analysis of CagA sequences showed the co-circulation of H. pylori of different geographical origins with Western sequences closer related to Cambodia, one of the entry of Western strains in Southeast-Asia through human migrations. Sequence analysis revealed in two Western type strains a chimeric CagA-3′ region with identity with East-Asian CagA suggesting recombination event in the process of evolution among East-Asian and Western H. pylori strains. Moreover, polymorphism in CagA multimerization (CM) motif was observed including new East-Asian CM motifs. In conclusion, we have found in central Vietnam a geographically dependent diversity of cagA genotype, with higher rates of cagA-negative and Western-type strains compared with other nation's parts that can partly explain the lower risk of gastric cancer. The polymorphism of CM motifs may explain the variability of disease manifestations of vacAs1i1m1 and s1i1m2 East-Asian isolates.

Cutoff Pepsinogen Level for Predicting Unintendedly Eradicated Cases of Helicobacter pylori Infection in Subjects with Seemingly Normal Pepsinogen Levels

Backgrounds/Aims: In the ABC method, which is a method for risk stratification of gastric cancer using serum anti-Helicobacter pylori antibody and pepsinogen (PG) test, subjects with normal PG and seronegative for H. pylori are named as “Group A” and are regarded as having a low risk of gastric cancer. These “Group A” subjects include unintentionally eradicated cases at relatively high risk, and this study aimed to identify these subjects. Methods: Of the 109 subjects, 76 were classified as uninfected Group A subjects with negative histologic H. pylori infection and no histologic and endoscopic atrophy, and 33 subjects were classified serologically as Group A after successful eradication, which are serologically equal to the unintendedly eradicated cases in Group A. The usefulness of measuring PG levels to detect post-eradication cases was validated by using a receiver operating characteristic (ROC) curve analysis. Results: The area under the ROC curve for PGI level was 0.736 ± 0.06 (p < 0.01; cutoff value, 37.0 ng/mL; sensitivity, 77.6%; specificity, 72.7%), and that for the PGI/II ratio was 0.660 ± 0.06 (p < 0.01; cutoff value, 5.1; sensitivity, 84.2%; specificity, 43.4%). Conclusion: PGI levels of ≤37 ng/mL and PGI/II ratios of ≤5.1 effectively identified unintendedly eradicated cases in Group A.