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Klesiewicz K, Orczykowska-Kotyna M, Skiba-Kurek I, Empel J, Kania K, Karczewska E. Prevalence and antimicrobial resistance of highly virulent cagA-positive Helicobacter pylori strains in Southern Poland. Eur J Clin Microbiol Infect Dis 2025; 44:405-416. [PMID: 39688753 DOI: 10.1007/s10096-024-05018-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 12/11/2024] [Indexed: 12/18/2024]
Abstract
PURPOSE Assessment of Helicobacter pylori (H. pylori) prevalence in Southern Poland, focusing on highly virulent cagA-positive strains associated with gastric cancer risk, along with analysis of antimicrobial resistance and its molecular mechanisms. METHODS A total of 130 dyspeptic patients, who underwent endoscopy, were enrolled in the study. Presence of H. pylori in gastric mucosa biopsy specimens was confirmed by rapid urease tests, histological examination, culture, and molecular assays. Antimicrobial susceptibility was tested using the E-test, while the cagA gene (virulence marker) was identified by PCR. The GenoType HelicoDR detected mutations for resistance to clarithromycin (23 S rRNA) and levofloxacin (gyrA). Resistance to rifampicin and levofloxacin was investigated by sequencing the rpoB and gyrA genes. RESULTS H. pylori prevalence in Southern Poland was 30.8%, with 60% of infections involving cagA-positive strains. Susceptibility testing revealed resistance rates of 22.9% for metronidazole, 14.3% for clarithromycin, 11.4% for levofloxacin and 25.7% for rifampicin. Among the 24 cagA-positive strains, 45.8% were resistant to at least one antibiotic. Clarithromycin resistance was caused by A2143G mutation. The gyrA gene sequence showed the N87K mutation linked to fluoroquinolone resistance. No mutations were found in the rpoB gene. CONCLUSION Infections with multidrug-resistant CagA-positive strains require recommended treatment strategies due to the high risk of progression of infection to gastric cancer.
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Affiliation(s)
- Karolina Klesiewicz
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, Krakow, 30-688, Poland.
| | - Monika Orczykowska-Kotyna
- Department of Epidemiology and Clinical Microbiology, National Medicines Institute, 30/34 Chełmska Street, Warsaw, 00-725, Poland
| | - Iwona Skiba-Kurek
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, Krakow, 30-688, Poland
| | - Joanna Empel
- Department of Epidemiology and Clinical Microbiology, National Medicines Institute, 30/34 Chełmska Street, Warsaw, 00-725, Poland
| | - Katarzyna Kania
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, Krakow, 30-688, Poland
- Microbiological Laboratory, The St. John Paul II Specialist Hospital, Pradnicka 80 Street, Krakow, 31-202, Poland
| | - Elżbieta Karczewska
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, Krakow, 30-688, Poland
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Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tran SC, Bryant KN, Cover TL. The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk. Gut Microbes 2024; 16:2314201. [PMID: 38391242 PMCID: PMC10896142 DOI: 10.1080/19490976.2024.2314201] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
Helicobacter pylori strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cag pathogenicity island (cag PAI). Colonization of the human stomach with cag PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cag PAI-negative strains. The cag PAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which H. pylori strains containing the cag PAI promote the development of gastric cancer and peptic ulcer disease.
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Affiliation(s)
- Sirena C. Tran
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kaeli N. Bryant
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Timothy L. Cover
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
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Grădinaru TC, Gilca M, Vlad A, Dragoș D. Relevance of Phytochemical Taste for Anti-Cancer Activity: A Statistical Inquiry. Int J Mol Sci 2023; 24:16227. [PMID: 38003415 PMCID: PMC10671173 DOI: 10.3390/ijms242216227] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Targeting inflammation and the pathways linking inflammation with cancer is an innovative therapeutic strategy. Tastants are potential candidates for this approach, since taste receptors display various biological functions, including anti-inflammatory activity (AIA). The present study aims to explore the power different tastes have to predict a phytochemical's anti-cancer properties. It also investigates whether anti-inflammatory phytocompounds also have anti-cancer effects, and whether there are tastes that can better predict a phytochemical's bivalent biological activity. Data from the PlantMolecularTasteDB, containing a total of 1527 phytochemicals, were used. Out of these, only 624 phytocompounds met the inclusion criterion of having 40 hits in a PubMed search, using the name of the phytochemical as the keyword. Among them, 461 phytochemicals were found to possess anti-cancer activity (ACA). The AIA and ACA of phytochemicals were strongly correlated, irrespective of taste/orosensation or chemical class. Bitter taste was positively correlated with ACA, while sweet taste was negatively correlated. Among chemical classes, only flavonoids (which are most frequently bitter) had a positive association with both AIA and ACA, a finding confirming that taste has predictive primacy over chemical class. Therefore, bitter taste receptor agonists and sweet taste receptor antagonists may have a beneficial effect in slowing down the progression of inflammation to cancer.
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Affiliation(s)
- Teodora-Cristiana Grădinaru
- Department of Functional Sciences I/Biochemistry, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Marilena Gilca
- Department of Functional Sciences I/Biochemistry, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Adelina Vlad
- Department of Functional Sciences I/Physiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Dorin Dragoș
- Department of Medical Semiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- 1st Internal Medicine Clinic, University Emergency Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050098 Bucharest, Romania
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Shirani M, Pakzad R, Haddadi MH, Akrami S, Asadi A, Kazemian H, Moradi M, Kaviar VH, Zomorodi AR, Khoshnood S, Shafieian M, Tavasolian R, Heidary M, Saki M. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis. BMC Infect Dis 2023; 23:543. [PMID: 37598157 PMCID: PMC10439572 DOI: 10.1186/s12879-023-08504-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 07/31/2023] [Indexed: 08/21/2023] Open
Abstract
BACKGROUND Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals. METHODS We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity. RESULTS Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%). CONCLUSIONS H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.
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Affiliation(s)
- Maryam Shirani
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Sousan Akrami
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Arezoo Asadi
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Kazemian
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Melika Moradi
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Vahab Hassan Kaviar
- Department of Medical Microbiology, Faculty of Medicine, Ilam University of Medical Science, Ilam, Iran
| | - Abolfazl Rafati Zomorodi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saeed Khoshnood
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Mahnaz Shafieian
- Department of Midwifery, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran
| | - Ronia Tavasolian
- Department of Medicine, Faculty of Nutrition Science, University of Cheste, Chester, UK
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Luo Y, Fu Y, Schwarz S, Wallach T. Comparison of Risk and Severity of Helicobacter Pylori Infection in Non-Native Versus US Native Pediatric Patients. JPGN REPORTS 2023; 4:e331. [PMID: 37600603 PMCID: PMC10435047 DOI: 10.1097/pg9.0000000000000331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 05/15/2023] [Indexed: 08/22/2023]
Abstract
INTRODUCTION Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients. METHODS We retrospectively reviewed all endoscopies with patients aged 1-21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations. RESULTS In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients. CONCLUSIONS Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.
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Affiliation(s)
- Yan Luo
- From the Department of Pediatrics, SUNY Downstate Health Sciences University
| | - Yinan Fu
- Department of Pediatric Gastroenterology, Children’s Hospital of Los Angeles
| | - Steven Schwarz
- Division of Pediatric Gastroenterology, Department of Pediatrics, SUNY Downstate Health Sciences University
| | - Thomas Wallach
- Division of Pediatric Gastroenterology, Department of Pediatrics, SUNY Downstate Health Sciences University
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Gu J, He F, Clifford GM, Li M, Fan Z, Li X, Wang S, Wei W. A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer. Expert Rev Mol Diagn 2023; 23:1251-1261. [PMID: 37905778 DOI: 10.1080/14737159.2023.2277377] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 10/03/2023] [Indexed: 11/02/2023]
Abstract
INTRODUCTION This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION CRD42021274120.
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Affiliation(s)
- Jianhua Gu
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Feifan He
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gary M Clifford
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Minjuan Li
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyuan Fan
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinqing Li
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shaoming Wang
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqiang Wei
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Application of Parametric Shared Frailty Models to Analyze Time-to-Death of Gastric Cancer Patients. J Gastrointest Cancer 2022; 54:104-116. [PMID: 35064523 DOI: 10.1007/s12029-021-00775-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Despite its declining incidence, gastric cancer (GC) is one of the world's leading malignancies and a major global health concern due to its high prevalence and fatality rate. Furthermore, it is the world's fourth most common cancer and the second leading cause of cancer death. Studying the determinants of time to death of gastric cancer patients will give clinicians more information to develop specific treatment plans, forecast prognosis, and track the progress of death cases. The application of the frailty model can help account for random variation in survival that may exist due to unobserved factors, as well as show the impact of latent factors on death risk. As a result, the purpose of this study was to assess the determinants of time to death of GC patients' by applying the parametric shared frailty models. METHODS The data for this study were obtained from gastric cancer patients admitted to the Tikur Anbesa Specialized Hospital, Addis Ababa, from January 1, 2015, to February 29, 2020. With the aim of coming up with an appropriate survival model that determines factors that affect the time to death of gastric cancer patients, various parametric shared frailty models were compared. In all of the frailty models, patient regions were used as a clustering variable. The current study implemented exponential, Weibull, log-logistic, and lognormal distributions for baseline hazard functions with gamma and inverse Gaussian's frailty distributions. The performance of all models was compared using the AIC and BIC criteria. R statistical software was used to conduct the analysis. RESULTS A retrospective study was undertaken on a total of 407 gastric cancer patients under follow-up at Tikur Anbesa Specialized Hospital. Of all 407 GC patients, 56.3% died while the remaining 43.7% were censored. The patients' median time to death was 21.9 months, with a maximum survival time of 49.6 months. In the current study, the clustering effect was significant in modeling the time to death from gastric cancer. The Weibull model with inverse Gaussian frailty has the minimum AIC and BIC value among the candidate models compared. The dependency within the clusters for the Weibull-inverse Gaussian frailty model was [Formula: see text] (13.4%). According to the results of our best model (Weibull-inverse Gaussian), the sex of the patient, the smoking status, the tumor size, the treatment taken, the vascular invasion, and the disease stage was found to be statistically significant at an alpha = 0.05 significance level. CONCLUSION Time to death of GC patient's data set was well described by the Weibull-inverse Gaussian shared frailty. Furthermore, Weibull baseline distribution best fits the GC data set as it enables proportional hazard and accelerated failure time model, for time to failure data. There is unobserved heterogeneity between clusters (patient regions), indicating the need to account for this clustering effect. In this study, survival time to death among GC patients was discovered to be small. Covariates like older age, being male, having higher (advanced) stage of GC disease (stage three and stage four), advanced tumor size, being smoker, infected by Helicobacter pylori, and existence of vascular invasion significantly accelerate the time to death of GC patients. In contrast, talking combination of more treatments prolongs the time to death of patients. To improve the health of patients, interventions should be taken based on significant prognostic factors, with special attention dedicated to patients with such factors to prevent GC death.
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Tang M, Shen X, Chai J, Cheng J, Wang D. Dose-Effect Relationship Between Gastric Cancer and Common Digestive Tract Symptoms and Diagnoses in Anhui, China. Cancer Manag Res 2021; 13:4955-4966. [PMID: 34188548 PMCID: PMC8235950 DOI: 10.2147/cmar.s313771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 05/29/2021] [Indexed: 11/23/2022] Open
Abstract
Background Early prevention and diagnosis are key to reducing the huge burden of gastric cancer (GC). Nearly half of the population worldwide are suffering from some form of digestive tract conditions (symptoms/diagnoses, DTCs) but their relations with GC are not well understood. We aim to explore the relationships (especially dose–effect relationships) between GC and DTCs. Methods This study used data from a community-based case–control study in Anhui, China during 2016–2019 and performed multivariate conditional logistic regression modeling of the associations between GC and DTCs. Results A total of 2255 participants (451 cases and 1804 controls) completed the study. Statistically significant relations (P<0.05) were found between GC and the presence of gastroesophageal reflux [odds ratio (OR)=1.41], odynophagia (OR=1.87), stomach discomfort (OR=1.86), poor appetite (OR=2.01) and Helicobacter pylori (H. pylori) infection (OR=4.39). When the DTCs were divided into duration grades, all these ORs presented an increasing trend (P<0.05), being 1.89 to 2.45 for gastroesophageal reflux, 1.63 to 3.78 for stomach discomfort, 2.36 to 5.29 for poor appetite, and 3.95 to 10.03 for H. pylori infection. When the DTCs were divided into severity grades, the ORs also witnessed an increasing trend (P<0.05), being 1.69 to 2.52 for gastroesophageal reflux, 2.44 to 3.56 for stomach discomfort, and 2.22 to 2.75 for poor appetite. When the DTCs were divided into duration-severity grades, the ORs displayed a much steeper increasing trend, being 0.49 to 4.96 for gastroesophageal reflux, 1.50 to 6.33 for odynophagia, 0.47 to 3.32 for stomach discomfort, and 0.40 to 10.47 for poor appetite. In contrast, the ORs for the lower DTCs were generally tested without statistical significance. Conclusion The study revealed consistent dose–effect associations between GC and duration of gastroesophageal reflux, stomach discomfort, poor appetite, and H. pylori infection; severity of gastroesophageal reflux, stomach discomfort and poor appetite; and duration-severity of gastroesophageal reflux, odynophagia, stomach discomfort and poor appetite. These should inform future prevention, diagnosis and further research in patients with GC.
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Affiliation(s)
- Mengsha Tang
- School of Public Health, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Xingrong Shen
- School of Health Service Management, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Jing Chai
- School of Health Service Management, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Jing Cheng
- School of Health Service Management, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Debin Wang
- School of Public Health, Anhui Medical University, Hefei, Anhui, People's Republic of China.,School of Health Service Management, Anhui Medical University, Hefei, Anhui, People's Republic of China
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Bornschein J, Quante M, Jansen M. The complexity of cancer origins at the gastro-oesophageal junction. Best Pract Res Clin Gastroenterol 2021; 50-51:101729. [PMID: 33975686 DOI: 10.1016/j.bpg.2021.101729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/08/2021] [Indexed: 01/31/2023]
Abstract
Chronic acid-biliary reflux and Helicobacter pylori infection are instrumental environmental drivers of cancer initiation and progression in the upper gastrointestinal tract. Remarkably, although these environmental carcinogens are quite dissimilar, the tumour progression cascade these carcinogens engender is highly comparable. For this reason, studies of malignant progression occurring at the anatomic borderland between the oesophagus and the stomach have traditionally lumped junctional adenocarcinomas with either oesophageal adenocarcinoma or gastric adenocarcinoma. Whilst studies have revealed remarkable epidemiological and genetic similarities of these cancers and their associated premalignant conditions, these works have also revealed some key differences. This highlights that further scientific effort demands a dedicated focus on the understanding of the cell-cell interaction between the epithelium and the local microenvironment in this anatomic region. We here review available evidence with regards to tumour progression occurring at the gastro-oesophageal junction and contrast it with available data on cancer evolution in the metaplastic oesophagus and distal stomach.
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Affiliation(s)
- Jan Bornschein
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom and NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
| | - Michael Quante
- Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Germany
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Crowley E, Hussey S. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:275-292.e12. [DOI: 10.1016/b978-0-323-67293-1.00027-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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12
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Huang Q, Read M, Gold JS, Zou XP. Unraveling the identity of gastric cardiac cancer. J Dig Dis 2020; 21:674-686. [PMID: 32975049 DOI: 10.1111/1751-2980.12945] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 08/11/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022]
Abstract
The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.
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Affiliation(s)
- Qin Huang
- Department of Pathology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China.,Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Matthew Read
- Department of Surgery, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Jason S Gold
- Department of Surgery, Veterans Affairs Boston Healthcare System, Harvard Medical School/Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Xiao Ping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, Jiangsu Province, China
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13
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Herrero R, Heise K, Acevedo J, Cook P, Gonzalez C, Gahona J, Cortés R, Collado L, Beltrán ME, Cikutovic M, Gonzalez P, Murillo R, Leja M, Megraud F, Hernandez MDLL, Barbier S, Park JY, Ferreccio C, for the ENIGMA Chile study group. Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile. PLoS One 2020; 15:e0237515. [PMID: 32898138 PMCID: PMC7478833 DOI: 10.1371/journal.pone.0237515] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 07/28/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.
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Affiliation(s)
- Rolando Herrero
- International Agency for Research on Cancer, Lyon, France
- Agencia Costarricense de Investigaciones Biomédicas, Fundación INCIENSA, Costa Rica
| | - Katy Heise
- Hospital Cancer Registry, Hospital Base Valdivia, Valdivia, Chile
| | | | - Paz Cook
- Public Health Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Advanced Center for Chronic Diseases, ACCDis, Santiago, Chile
| | - Claudia Gonzalez
- Secretaría Regional Ministerial de Salud, Antofagasta Region, Chile
| | - Jocelyne Gahona
- Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta, Chile
| | - Raimundo Cortés
- Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta, Chile
| | - Luis Collado
- Institute of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Valdivia, Chile
| | | | - Marcos Cikutovic
- Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta, Chile
| | - Paula Gonzalez
- Agencia Costarricense de Investigaciones Biomédicas, Fundación INCIENSA, Costa Rica
| | - Raul Murillo
- International Agency for Research on Cancer, Lyon, France
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Francis Megraud
- Bordeaux University, INSERM, UMR1053, BaRITOn, Team 2 "Helicobacter Infection, Inflammation and Cancer", Bordeaux, France
- Pellegrin University Hospital, Bacteriology Laboratory, French National Reference Center for Campylobacters and Helicobacters, Bordeaux, France
| | | | | | - Jin Young Park
- International Agency for Research on Cancer, Lyon, France
| | - Catterina Ferreccio
- Public Health Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Advanced Center for Chronic Diseases, ACCDis, Santiago, Chile
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14
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Panarese A, Galatola G, Armentano R, Pimentel-Nunes P, Ierardi E, Caruso ML, Pesce F, Lenti MV, Palmitessa V, Coletta S, Shahini E. Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions. World J Gastroenterol 2020; 26:3834-3850. [PMID: 32774061 PMCID: PMC7383846 DOI: 10.3748/wjg.v26.i26.3834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/20/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection has been associated with a long-term risk of precancerous gastric conditions (PGC) even after H. pylori eradication. AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC, before/after H. pylori eradication. METHODS We studied 85 consecutive patients with H. pylori-related gastritis with/without PGC before and 6 mo after proven H. pylori eradication. Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications, were applied to assess the endoscopic extension of atrophy and intestinal metaplasia. The histological result was considered to be the gold standard. The Sydney System, the Operative-Link on Gastritis-Assessment, and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis, atrophy and intestinal metaplasia, whereas dysplasia was graded according to World Health Organization classification. Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected. RESULTS After H. pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia, disappeared or decreased in 100% and 96.5% of patients respectively, whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change. Low-Grade Dysplasia prevalence was similar on random biopsies before and after H. pylori eradication (17.6% vs 10.6%, P = 0.19), but increased in patients with visible lesions (0% vs 22.4%, P < 0.0001). At a multivariate analysis, the probability for detecting dysplasia after resolution of H. pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia, greater alcohol consumption, and anti-parietal cell antibody and/or anti-intrinsic factor positivity [odds ratio (OR) = 3.88, 95% confidence interval (CI): 1.31-11.49, P = 0.01; OR = 3.10, 95%CI: 1.05-9.12, P = 0.04 and OR = 5.47, 95%CI: 1.33-22.39, P < 0.04, respectively]. CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H. pylori-induced chronic gastritis. Patients with an overlap between autoimmune/H. pylori-induced gastritis may require more extensive gastric mapping.
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Affiliation(s)
- Alba Panarese
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Raffaele Armentano
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Pedro Pimentel-Nunes
- Center for Research in Health Technologies and Information Systems, Faculty of Medicine, Porto 4200072, Portugal
- Surgery and Physiology Department, Faculty of Medicine of the University of Porto, Porto 4200072, Portugal
| | - Enzo Ierardi
- Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Lucia Caruso
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Francesco Pesce
- Nephrology Section, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia 27100, Italy
| | - Valeria Palmitessa
- Laboratory of Microbiology and Virology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Endrit Shahini
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
- Giovanni Galatola Gastroenterology Unit, Institute for Cancer Research and Treatment, Turin 10121, Italy
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15
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Holleczek B, Schöttker B, Brenner H. Helicobacter pylori
infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population‐based ESTHER cohort study. Int J Cancer 2020; 146:2773-2783. [DOI: 10.1002/ijc.32610] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/14/2019] [Accepted: 07/19/2019] [Indexed: 12/24/2022]
Affiliation(s)
- Bernd Holleczek
- Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center (DKFZ) Heidelberg Germany
- Saarland Cancer Registry Saarbrücken Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center (DKFZ) Heidelberg Germany
- Network Aging Research, University of Heidelberg Heidelberg Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research Center (DKFZ) Heidelberg Germany
- Division of Preventive OncologyGerman Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg Germany
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16
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Yin JJ, Duan FJ, Madhurapantula SV, Zhang YH, He G, Wang KY, Ji XK, Wang KJ. Helicobacter pylori and gastric cardia cancer: What do we know about their relationship? World J Meta-Anal 2020; 8:89-97. [DOI: 10.13105/wjma.v8.i2.89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 02/08/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
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17
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Gotland N, Uhre M, Sandholdt H, Mejer N, Lundbo L, Petersen A, Larsen A, Benfield T. Increased risk of incident primary cancer after Staphylococcus aureus bacteremia: A matched cohort study. Medicine (Baltimore) 2020; 99:e19984. [PMID: 32332684 PMCID: PMC7220765 DOI: 10.1097/md.0000000000019984] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Susceptibility to infectious disease may be a marker of immunodeficiency caused by unrecognized cancer. To test the hypothesis, the risk of incident primary cancer was estimated among survivors of Staphylococcus aureus bacteremia (SAB) and compared to a random population cohort.Nation-wide population-based matched cohort study. Cases of SAB were identified from a national database and incident primary cancers were ascertained by record linkage. Incidence rate (IR) and ratio (IRR) with 95% confidence interval (CI) of 27 cancers was calculated by Poisson regression.During the first year of follow-up, 165 and 943 incident cases of cancer occurred in the case cohort (n = 12,918 (1.3%)) and the population cohort (n = 117,465 (0.8%)) for an IR of 3.78 (3.22-4.40) and 2.28 (2.14-2.43) per 100,000 person-years. The IRR was 1.65 (1.40-1.95). Of 27 cancers, 7 cancers occurred more frequently amongst cases than controls: cervical cancer (IRR 37.83 (4.23-338.47)), multiple myeloma (IRR 6.31 (2.58-15.44)), leukemia (IRR 4.73 (2.21-10.10)), sarcoma (IRR 4.73 (1.18-18.91)), liver cancer (IRR 3.64 (1.30-10.21)), pancreatic cancer (IRR 2.8 (1.27-6.16)), and urinary tract cancer (IRR 2.58 (1.23-5.39)). Compared to the control population, the risk of cancer was higher for those without comorbidity and with younger age. The overall risk of cancer during 2 to 5 years of follow-up was not increased (IRR 0.99 (95% CI: 0.89-1.11). However, the risk of pharyngeal cancer was increased (IRR 1.88 (1.04-3.39)) and the risk of liver cancer remained increased (IRR 3.93 (2.36-6.55)).The risk of primary incident cancer was 65% higher in the SAB cohort compared to the population cohort during the first year of follow-up and included 7 specific cancers. The risk was higher for those without comorbidity and with younger age. Screening for these specific cancers in selected populations may allow for earlier detection.
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Affiliation(s)
- Nanja Gotland
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
| | - M.L. Uhre
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
| | - H. Sandholdt
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
| | - N. Mejer
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
| | - L.F. Lundbo
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
| | - A. Petersen
- Reference Laboratory for Antimicrobial Resistance and Staphylococci, Statens Serum Institut
| | - A.R. Larsen
- Reference Laboratory for Antimicrobial Resistance and Staphylococci, Statens Serum Institut
| | - T. Benfield
- Department of Infectious Diseases, Amager Hvidovre Hospital, University of Copenhagen, Hvidovre
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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18
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Xie S, Wang S, Xue L, Middleton DRS, Guan C, Hao C, Wang J, Li B, Chen R, Li X, Wei W. Helicobacter pylori Is Associated With Precancerous and Cancerous Lesions of the Gastric Cardia Mucosa: Results of a Large Population-Based Study in China. Front Oncol 2020; 10:205. [PMID: 32195175 PMCID: PMC7063085 DOI: 10.3389/fonc.2020.00205] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 02/06/2020] [Indexed: 12/22/2022] Open
Abstract
Background: Helicobacter pylori (H. pylori) is widely accepted to be the most important cause of gastric non-cardia adenocarcinoma (GNCA), while its role in the development of gastric cardia adenocarcinoma (GCA) is not well-defined. We aimed to investigate current H. pylori infection in relation to the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. Methods: A population-based cross-sectional study was conducted in Linzhou County, Henan Province, China. Two thousand three (2,003) randomly selected participants with data on current H. pylori infection, assayed by 13C-urea breath test (13C-UBT), and a sequence of histological diagnoses of the gastric cardia mucosa were analyzed. Results: Of 2,003 subjects, 828 (41.33%) were currently infected with H. pylori. The prevalence of current H. pylori infection increased with increasing severity of histological lesions, from 34.12% in subjects with normal gastric cardia mucosa to 52.17% in subjects with gastric cardia high-grade intraepithelial neoplasia (CHIN)/ gastric cardia adenocarcinoma (GCA) (P for trend <0.001). With H. pylori-negative subjects as the reference category, H. pylori-positive subjects had statistically significant elevated adjusted prevalence odds ratios (PORs) for each of the histological lesions. The PORs (95% CI) were 2.15 (1.74-2.64), 3.46 (2.08-5.75), 2.78 (1.90-4.07), and 3.05 (1.30-7.17) for subjects with carditis, cardia intestinal metaplasia (CIM), cardia low-grade intraepithelial neoplasia (CLIN), and CHIN/GCA), respectively. The associations remained when subjects with abnormal stomach non-cardia mucosa were excluded. Conclusions: This large epidemiologic study demonstrates a positive association between current H. pylori infection and the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. These findings suggest that H. pylori infection may play a role throughout both early- and late-stage development of GCA.
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Affiliation(s)
- Shuanghua Xie
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shaoming Wang
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Daniel R S Middleton
- Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France
| | - Chentao Guan
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Changqing Hao
- Department of Endoscopy, Cancer Institute/Hospital of Linzhou, Linzhou, China
| | - Jinwu Wang
- Department of Pathology, Cancer Institute/Hospital of Linzhou, Linzhou, China
| | - Bianyun Li
- Department of Epidemiology, Cancer Institute/Hospital of Linzhou, Linzhou, China
| | - Ru Chen
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinqing Li
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqiang Wei
- National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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19
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Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children. J Gastroenterol 2018; 53:718-724. [PMID: 29110085 DOI: 10.1007/s00535-017-1406-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 10/25/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Helicobacter pylori infection is a risk factor for gastric cancer, and it has been reported that eradication of H. pylori is effective for preventing such cancer. Recently, H. pylori eradication has been performed in children as first-line therapy against gastric cancer. Here, we report use of triple therapy with a potassium-competitive acid blocker (P-CAB) for H. pylori eradication in children. METHODS H. pylori infection testing and eradication therapy began in fiscal year 2015 in junior high school students located in Yurihonjo city and Nikaho city, Akita prefecture, Japan. Urine-based immunochromatography, stool antigen enzyme-linked immunosorbent assay tests, and serum antibody tests were performed as the initial screening examination. Those who tested positive on one of the three examinations then underwent a urea breath test (13C-UBT). Those who tested positive on 13C-UBT and expressed the desire to undergo H. pylori eradication then received eradication therapy comprising 20 mg P-CAB, 750 mg amoxicillin, and 200 mg clarithromycin twice a day for 7 days. At least 8 weeks after treatment, eradication success was evaluated using 13C-UBT. RESULTS A total of 118 students received eradication therapy. Eradication rates were 81.3% (95% confidence interval: 74.3-88.4, 96/118) in ITT analysis and 85.7% (95% confidence interval: 79.1-92.9 96/112) in PP analysis. Adverse effects associated with eradication therapy were observed in 25 of 118 subjects (21.1%), seven of whom required hospital treatment (rash in five, vomiting in two). All seven subjects either discontinued therapy or were administered anti-allergy drugs, which resulted in swift alleviation of symptoms. CONCLUSIONS First-line triple therapy with a P-CAB for H. pylori eradication in children was found to be safe.
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20
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Kamogawa-Schifter Y, Yamaoka Y, Uchida T, Beer A, Tribl B, Schöniger-Hekele M, Trauner M, Dolak W. Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years. PLoS One 2018; 13:e0197695. [PMID: 29813089 PMCID: PMC5973618 DOI: 10.1371/journal.pone.0197695] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 05/07/2018] [Indexed: 12/11/2022] Open
Abstract
Background and aims The prevalence of Helicobacter pylori (H. pylori) tends to be lower in Western countries such as central Europe compared with Asia. The virulence of H. pylori is influenced by its subtype composition, most importantly by the presence or absence of different types of cytotoxin-associated gene A(CagA). This study aimed to assess the prevalence of H. pylori and its respective CagA phenotype in a large retrospective cohort of patients with gastric cancer or duodenal ulcer at a Western tertiary referral institution. Methods H. pylori positive gastric biopsy samples from patients diagnosed with the afore mentioned diseases within the past 25 years were re-evaluated by histology for H. pylori and status of gastritis. Confirmed H. pylori positive cases were processed for immunohistochemistry (IHC) for H. pylori,CagA, and EastAsiantype CagA. Results The prevalence of H. pylori positive gastric biopsy samples decreased from 20.7% to 2.3% within the study period. Among the gastric cancer patients, the H. pylori positive rate was 16.6%, and didn’t show significant changes over time (p = 0.38). Contrary, the H. pylori positive rate of duodenal ulcer decreased significantlyfrom 40% to 5% (p = 0.01). Within H. pylori positive groups ofboth diseases, CagA was highly detected at IHC (86% and 78%, respectively). Except for a few patients originating from East Asian countries, all CagA detected in this study were of Western type. Conclusion In this first Western investigation on the chronological prevalence of H. pylori and its most relevant subtypes, Western type of CagA was highly detected in two important index diseases of the pathogen. This raises further questions about the virulence of this subtype.
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Affiliation(s)
- Yumiko Kamogawa-Schifter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu-city, Oita, Japan
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu-city, Oita, Japan
| | - Andrea Beer
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Barbara Tribl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Maximilian Schöniger-Hekele
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Werner Dolak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- * E-mail:
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21
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Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE. Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer. Toxins (Basel) 2018; 10:E163. [PMID: 29671784 PMCID: PMC5923329 DOI: 10.3390/toxins10040163] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/10/2018] [Accepted: 04/10/2018] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95⁻4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58⁻3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46⁻0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies.
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Affiliation(s)
- Jin Young Park
- International Agency for Research on Cancer, 69372 Lyon, France.
| | - David Forman
- International Agency for Research on Cancer, 69372 Lyon, France.
| | - Langgeng Agung Waskito
- Institute of Tropical Disease, Universitas Airlangga, Surabaya 60113, Indonesia.
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Oita 879-5503, Japan.
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Oita 879-5503, Japan.
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
| | - Jean E Crabtree
- Leeds Institute Biomedical and Clinical Sciences, Wellcome Trust Brenner Building, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, UK.
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Gorini G, Giovannetti L, Masala G, Chellini E, Martini A, Mallone S, Costantini AS. Gastric Cancer Mortality Trends in Tuscany, Italy, 1971–2004. TUMORI JOURNAL 2018; 94:787-92. [DOI: 10.1177/030089160809400602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Aims, Background, and Methods In Tuscany, Italy, gastric cancer mortality has been decreasing since 1950, although with relevant geographical variability across the region. In Eastern Tuscan areas close to the mountains (high risk areas), gastric cancer mortality has been and is still significantly higher than that recorded in Western coastal areas and in the city of Florence (low risk areas). High-risk areas also showed higher Helicobacter pylori seroprevalence. Aim of this paper is to study gastric cancer mortality trends in high and low-risk areas, during the period 1971–2004, using age-period-cohort models. Results In high-risk areas, gastric cancer mortality rates declined from 61.4 per 100,000 in 1971–74 to 19.8 in 2000–2004 and in low-risk areas from 34.9 to 9.8. Mortality decline in high-risk areas was mainly attributable to a birth cohort effect, whereas in low-risk areas it was due either to a birth cohort effect or a period effect. In low- and high-risk areas, birth-cohort risks of dying decreased over subsequent generations, except for the birth cohorts born around the second world war. Conclusions Gastric cancer mortality in areas with higher H. pylori seroprevalence in Tuscany (high-risk areas) showed a predominant decline by birth cohort, in particular for younger generations, possibly due to the decrease of the infection for improvement of living conditions.
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Affiliation(s)
- Giuseppe Gorini
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Lucia Giovannetti
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Giovanna Masala
- Molecular and Nutritional Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Elisabetta Chellini
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Andrea Martini
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Sandra Mallone
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
| | - Adele Seniori Costantini
- Environmental and Occupational Epidemiology Unit, Institute for Study and Prevention of Cancer, Florence, Italy
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The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients. Int J Mol Sci 2018; 19:ijms19020338. [PMID: 29364158 PMCID: PMC5855560 DOI: 10.3390/ijms19020338] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 01/09/2018] [Accepted: 01/18/2018] [Indexed: 12/18/2022] Open
Abstract
Helicobacter pylori (Hp) is one of the most important human pathogens that can cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is considered to be a cause of limiting access to bariatric surgery. The aim of this study was to determine the prevalence of Hp in patients with obesity going into bariatric surgery and to reveal the relationship between Hp and clinical data. The study group was formed of 68 preoperative bariatric surgery patients (body mass index (BMI) 44.7 ± 4.8). Gastric biopsies (antrum and corpus) were used for histological and molecular (caqA and glmM genes) examinations. The PCR method revealed Hp infection in 64.7% of obese patients that is higher in comparison with histological analysis (55.9%). The prevalence of cagA and glmM genes in antrum mucosa was 45.6% and 47.0% while in the corpus it was 41.2% and 38.3%, respectively. The coincidence of both cagA and glmM virulence genes in the antrum and corpus mucosa was 33.8% and 22.1%, respectively. Either of the genes was found in 58.8% of antrum and 57.3% of corpus mucosa. Presence of caqA and glmM genes was in association with active and atrophic chronic gastritis. In conclusion, our study demonstrated that two thirds of morbidly obese patients undergoing bariatric surgery are infected with Hp and have a high prevalence of cagA and glmM virulence genes that points out the necessity for diagnostics and treatment of this infection before surgery.
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Prevalence and characteristics of Epstein-Barr virus-associated gastric carcinomas in Portugal. Infect Agent Cancer 2017; 12:41. [PMID: 28814970 PMCID: PMC5518146 DOI: 10.1186/s13027-017-0151-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/10/2017] [Indexed: 12/17/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein–Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population. Methods In the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR. Results EBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%). Conclusions The present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient’s survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.
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Abstract
Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.
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Carrera-Lasfuentes P, Lanas A, Bujanda L, Strunk M, Quintero E, Santolaria S, Benito R, Sopeña F, Piazuelo E, Thomson C, Pérez-Aisa A, Nicolás-Pérez D, Hijona E, Espinel J, Campo R, Manzano M, Geijo F, Pellise M, Zaballa M, González-Huix F, Espinós J, Titó L, Barranco L, D'Amato M, García-González MA. Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype. Oncotarget 2017; 8:35848-35862. [PMID: 28415781 PMCID: PMC5482622 DOI: 10.18632/oncotarget.16261] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 02/27/2017] [Indexed: 12/21/2022] Open
Abstract
Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55-2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22-2.57), and family history of GC (OR: 2.87; 95% CI: 1.85-4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56-0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56-0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38-0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30-2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.
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Affiliation(s)
| | - Angel Lanas
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
- Faculty of Medicine, Universidad de Zaragoza, Zaragoza, Spain
| | - Luis Bujanda
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Mark Strunk
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
| | - Enrique Quintero
- Department of Gastroenterology, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB), Centro de Investigación Biomédica de Canarias (CIBICAN), Tenerife, Spain
| | | | - Rafael Benito
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
- Faculty of Medicine and Department of Microbiology, Hospital Clínico Universitario, Zaragoza, Spain
| | - Federico Sopeña
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Elena Piazuelo
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
- Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
| | - Concha Thomson
- Department of Gastroenterology, Hospital Obispo Polanco, Teruel, Spain
| | | | - David Nicolás-Pérez
- Department of Gastroenterology, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB), Centro de Investigación Biomédica de Canarias (CIBICAN), Tenerife, Spain
| | - Elizabeth Hijona
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Jesús Espinel
- Department of Gastroenterology, Complejo Hospitalario, León, Spain
| | - Rafael Campo
- Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain
| | - Marisa Manzano
- Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
| | - Fernando Geijo
- Department of Gastroenterology, Hospital Clínico Universitario, Salamanca, Spain
| | - María Pellise
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Gastroenterology, Hospital Clinic I Provincial, Institut d Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain
| | - Manuel Zaballa
- Department of Gastroenterology, Hospital de Cruces, Barakaldo, Spain
| | | | - Jorge Espinós
- Department of Gastroenterology, Mutua de Tarrasa, Spain
| | - Llúcia Titó
- Department of Gastroenterology, Hospital de Mataró, Mataró, Spain
| | - Luis Barranco
- Department of Gastroenterology, Hospital del Mar, Barcelona, Spain
| | - Mauro D'Amato
- BioDonostia Health Research Institute, IKERBASQUE, Basque Foundation for Science, San Sebastián, Spain
| | - María Asunción García-González
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
- Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
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Li Q, Liu J, Gong Y, Yuan Y. Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer and gastric cancer risks: A meta-analysis. Medicine (Baltimore) 2017; 96:e6620. [PMID: 28445260 PMCID: PMC5413225 DOI: 10.1097/md.0000000000006620] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Increasingly, studies have focused on the relationship between Helicobacter pylori (H pylori) cytotoxin associated gene A protein (CagA) Glu-Pro-Ile-Tyr-Ala (EPIYA)-D motifs or multiple EPIYA-C phosphorylation sites and peptic ulcer disease (PUD) or gastric cancer (GC) risk. However, the conclusions have been inconsistent. The aim of this meta-analysis was to evaluate whether 1 CagA EPIYA-D motif or multiple EPIYA-C phosphorylation sites were associated with PUD or GC risk. MATERIALS AND METHODS A literature search was performed in PubMed, Web of Science, Wanfang Data, Excerpt Medica Database, and the Chinese National Knowledge Infrastructure database to identify eligible research. We analyzed the odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of association. RESULTS Compared with 1 EPIYA-C motif in Asian populations, 1 EPIYA-D site was associated with an increased GC risk (OR=1.91, 95% CI=1.19-3.07, P = .008). However, 1 EPIYA-D motif was not significantly associated with PUD (OR = 0.90, 95% CI = 0.46-1.76, P = .764), gastric ulcer (GU) (OR = 0.85, 95% CI = 0.27-2.63, P = .771), or duodenal ulcer (DU) (OR = 0.89, 95% CI = 0.25-3.16, P = .859) risk. Compared with no more than 1 EPIYA-C motif, multiple motifs were associated with increased PUD (OR = 2.33, 95% CI = 1.29-4.20, P = .005) and DU (OR = 2.32, 95% CI = 1.08-5.00, P = .031) risk in Asia and GC risk in the United States and Europe (OR = 3.28, 95% CI = 2.32-4.64, P < .001). Multiple EPIYA-C sites were not associated with GU risk (OR = 4.54, 95% CI = 0.95-21.83, P = .059). There was no publication bias identified in these comparisons. CONCLUSIONS In Asia, 1 EPIYA-D motif was significantly associated with increased GC risk. Multiple EPIYA-C motifs were associated with increased PUD and DU risk, particularly in Asia. In the United States and Europe, multiple EPIYA-C motifs were associated with increased GC risk. Therefore, detection of polymorphic CagA EPIYA motifs may improve clinical prediction of disease risk.
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28
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Figueiredo C, Camargo MC, Leite M, Fuentes-Pananá EM, Rabkin CS, Machado JC. Pathogenesis of Gastric Cancer: Genetics and Molecular Classification. Curr Top Microbiol Immunol 2017. [PMID: 28124158 DOI: 10.1007/978-3-319-50520-6_12.erratum.in:currtopmicrobiolimmunol.2017;400:e1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023]
Abstract
Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.
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Affiliation(s)
- Ceu Figueiredo
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.,Faculty of Medicine of the University of Porto, Porto, Portugal
| | - M C Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, ML, USA
| | - Marina Leite
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal
| | - Ezequiel M Fuentes-Pananá
- Research Unit of Cancer and Virology, Children's Hospital of Mexico "Federico Gomez", Mexico City, Mexico
| | - Charles S Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, ML, USA
| | - José C Machado
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. .,Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal. .,Faculty of Medicine of the University of Porto, Porto, Portugal.
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Ghatak S, Yadav RP, Lalrohlui F, Chakraborty P, Ghosh S, Ghosh S, Das M, Pautu JL, Zohmingthanga J, Senthil Kumar N. Xenobiotic Pathway Gene Polymorphisms Associated with Gastric Cancer in High Risk Mizo-Mongoloid Population, Northeast India. Helicobacter 2016; 21:523-535. [PMID: 27006283 DOI: 10.1111/hel.12308] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the risk of gastric cancer associated with individual or combined glutathione S-transferases (GSTs) polymorphism and their interaction with environmental factors. MATERIALS AND METHODS Genotyping by PCR was carried out for 80 cases and controls each for GSTM1, GSTT1, and GSTP1 polymorphism and mapped for gene-environment association studies. The samples were subjected to pathogen detection and GSTP1 expression for analyzing their association with different genotypes. Logistic regression analyses were conducted to compute the influence of both genetic and environmental factors for gastric cancer. MDR analysis was performed to assess the risk of gastric cancer by studying the gene-gene and gene-environment effect on the basis of GST genotyping and GSTP1 gene expression. RESULTS Infection with Helicobacter pylori and CagA+ strains was more frequent in patients with GSTM1/T1 null genotype. Intake of high fermented fat and smoked meat was found to be significantly associated with gastric cancer. The G/G, A/G (rs1695), and T/T (rs1138272) were found to be significantly associated with low expression of GSTP1 gene in cancer tissue. CONCLUSION Presence of H. pylori with CagA genotype showed significant individual effect with GSTT1 polymorphism as well as strong synergistic effect in gastric cancer risk. Majority of the gastric cancer samples showed significant negative expression in G/G, A/G (rs1695), and T/T (rs1138272) genotypes. This study shows that GST gene polymorphism was significantly relevant for determining the individual susceptibility to gastric cancer.
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Affiliation(s)
- Souvik Ghatak
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | | | - Freda Lalrohlui
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Payel Chakraborty
- Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India
| | - Soumee Ghosh
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
| | - Sudakshina Ghosh
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
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Vohlonen I, Pukkala E, Malila N, Härkönen M, Hakama M, Koistinen V, Sipponen P. Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up. Scand J Gastroenterol 2016; 51:1159-64. [PMID: 27338132 PMCID: PMC4960513 DOI: 10.1080/00365521.2016.1183225] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We investigated the risk of gastric cancer among men with Helicobacter pylori (H. pylori) infection or atrophic gastritis (AG) in a 15-year follow-up. MATERIALS AND METHODS Study population consists of 12,016 men aged 50-65 years at the beginning of the follow-up in 1994-1996. Serum levels of pepsinogen I (SPGI) and antibodies (IgG) to H. pylori (HpAb) were assayed from serums collected in 1994-1996. Incidence of gastric cancer in the study population was assessed in follow-up from 1994 to 2011 by data from the nationwide cancer registry. Based on SPGI and HpAb values, standardized incidence ratios (SIRs) of gastric cancer were calculated in three subgroups, that is, in those with a healthy stomach, those with H. pylori infection but without AG and those with AG. Risk ratios (RR) of gastric cancer were calculated using SIR of subgroups. RESULTS During 15 years, seven gastric cancers appeared per 79,928 person years among men with healthy stomachs, 50 cancers per 92,533 person years in men with H. pylori infection but without AG, and 8 per 8658 person years in men with AG. Risk ratio (RR) of stomach cancer in men with H. pylori infection was 5.8 (95%CI: 2.7-15.3) compared to men with healthy stomachs, and 9.1 (95%CI: 2.9-30.0) in men with AG. There were no differences in cancer risk between cardia and distal stomach. CONCLUSIONS Risk of gastric cancer is low in men with healthy stomachs. It is significantly increased in those with H. pylori infection and more in those with AG.
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Affiliation(s)
- Ilkka Vohlonen
- Department of Public Health, University of Eastern Finland,
Kuopio,
Finland,CONTACT Ilkka Vohlonen University of Eastern Finland, Public Health, BOX 1627,
Kuopio70100,
Finland
| | | | - Nea Malila
- Department of Epidemiology, Finnish Cancer Registry,
Helsinki,
Finland
| | - Matti Härkönen
- Department of Clinical Chemistry, University of Helsinki,
Helsinki,
Finland
| | - Matti Hakama
- Department of Epidemiology, Finnish Cancer Registry,
Helsinki,
Finland
| | - Veli Koistinen
- Department of Biostatistics, Finnish Consulting Group,
Helsinki,
Finland
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Zhang Y, Wang H, Bi C, Xiao Y, Liu Z. Expression of CDX2 in gastric cardia adenocarcinoma and its correlation with H. pylori and cell proliferation. Oncotarget 2016; 7:54973-54982. [PMID: 27384681 PMCID: PMC5342395 DOI: 10.18632/oncotarget.10362] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2015] [Accepted: 06/12/2016] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastric cardia cancer (GCC) is located in the distal stomach, and strongly correlates with atrophic gastritis and Helicobacter pylori (H.pylori) infection. Caudal-related homeobox transcription factor 2 (CDX2) is homeobox gene encoding an intestine-specific transcription factor usually expressed in the intestinal epithelium cells. However, in several recent published papers, CDX2 was found to be aberrantly expressed in gastric, thyroid and ovarian cancer. RESULTS Higher expression of CDX2 was found in GCC tissues in comparison with non-malignant cardia mucosa (p<0.05). Moreover, immunohistochemical analysis demonstrated that CDX2 expression correlated with lymphatic metastasis. In addition, we found that CDX2 expression progressively increased with the level of H. pylori infection (p<0.05), and also correlated with cell proliferation, based on Ki67 staining. METHODS To investigate the relationship between CDX2, cell proliferation and H. pylori infection, we detected CDX2, Ki62 and H.pylori expression in 83 non-malignant gastric cardia mucosacases and 60 GCC specimens in the Chaoshan area, a high-risk region for esophageal and gastric cardia cancer. CONCLUSION These findings provide pathological evidence that H. pylori infectionis a driving force of gastric cardia carcinogenesis by upregulating CDX2 and inducing inflammation. These results provide new pathological evidence that H. pylori infection induces GCC tumorigenesis.
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Affiliation(s)
- Ying Zhang
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Hu Wang
- Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Chao Bi
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Yinping Xiao
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Zhaoyong Liu
- Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
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Moaddeb A, Fattahi MR, Firouzi R, Derakhshandeh A, Farshad S. Genotyping of the Helicobacter pylori cagA Gene Isolated From Gastric Biopsies in Shiraz, Southern Iran: A PCR-RFLP and Sequence Analysis Approach. Jundishapur J Microbiol 2016; 9:e30046. [PMID: 27335631 PMCID: PMC4914860 DOI: 10.5812/jjm.30046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 09/23/2015] [Accepted: 09/23/2015] [Indexed: 01/05/2023] Open
Abstract
Background Cytotoxin-associated gene A (cagA) is an important virulence factor in the pathogenesis of Helicobacter pylori. Objectives The aim of this study was to genotype the H. pylori cagA gene isolated from antral biopsies of patients with stomach symptoms, using a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. Patients and Methods A total of 161 gastric biopsies were collected from patients with stomach symptoms. After isolation of H. pylori from the biopsy culture, the cagA gene was assessed using PCR. The PCR products were then digested by the HinfI restriction endonuclease enzyme. A sample of each genotype was also subjected to direct sequencing for further analysis. Results From 161 antral biopsies, 61 (37.9%) were positive for H. pylori in culture. Overall, 24 cagA-positives were detected in the isolates. RFLP indicated three different genotypes (I, II, and III) of cagA with a frequency of 62.5%, 25%, and 12.5% among the isolates, respectively. Genotypes I and II of cagA were predominant in patients who had gastritis. However, genotype III was found in three patients with duodenitis and duodenal ulcers. Alignment of the nucleotide sequences of the three isolated genotypes, with H. pylori 26695 as a reference strain, revealed 12 inserted nucleotides in genotype III. When the sequence of genotype III was aligned with 15 additional H. pylori strains available in GenBank, the same inserted nucleotides were detected in six of them. Conclusions Using the PCR-RFLP method, three distinctive H. pylori cagA genotypes were detected in antral biopsies. Genotype I, which was predominant among the isolates, was significantly associated with gastritis. However, the data showed that cagA genotype III may play a role in duodenitis and duodenal ulcers in patients infected with H. pylori.
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Affiliation(s)
- Afsaneh Moaddeb
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Mohammad Reza Fattahi
- Gastroentrohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Roya Firouzi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Abdollah Derakhshandeh
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Shohreh Farshad
- Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding author: Shohreh Farshad, Clinical Microbiology Research Center, Shiraz University of Medical Sciences, P. O. Box: 7193711351, Shiraz, IR Iran. Tel: +98-7136474304; +98-9173173501, Fax: +98-7136474303, E-mail:
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Søgaard KK, Farkas DK, Pedersen L, Lund JL, Thomsen RW, Sørensen HT. Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers. Cancer Med 2016; 5:1341-51. [PMID: 26923747 PMCID: PMC4924392 DOI: 10.1002/cam4.680] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 01/11/2016] [Accepted: 02/01/2016] [Indexed: 12/31/2022] Open
Abstract
Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994-2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori-related) and gastric ulcers (dominantly lifestyle-related) compared with the general population. We started follow-up 1-year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1-5-year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31-1.44) and 1.30 (95% CI: 1.23-1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking- and alcohol-related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized.
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Affiliation(s)
- Kirstine K Søgaard
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Dóra K Farkas
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Pedersen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Jennifer L Lund
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | - Reimar W Thomsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik T Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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Liou JM, Lin JT, Wu MS. Prevention of Gastric Cancer by Helicobacter pylori Eradication: Current Evidence and Future Prospects. HELICOBACTER PYLORI 2016:181-202. [DOI: 10.1007/978-4-431-55705-0_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CSPM, Peeters PHM, González CA, Zamora-Ros R, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Fagherazzi G, Racine A, Kühn T, Katzke V, Boeing H, Trichopoulou A, Trichopoulos D, Lagiou P, Palli D, Grioni S, Vineis P, Tumino R, Panico S, Weiderpass E, Skeie G, Braaten T, Huerta JM, Sánchez-Cantalejo E, Barricarte A, Sonestedt E, Wallstrom P, Nilsson LM, Johansson I, Bradbury KE, Khaw KT, Wareham N, Huybrechts I, Freisling H, Cross AJ, Riboli E, Bueno-de-Mesquita HB. Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study. Int J Cancer 2015; 136:E720-30. [PMID: 25236393 DOI: 10.1002/ijc.29223] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Revised: 08/12/2014] [Accepted: 08/15/2014] [Indexed: 01/13/2023]
Abstract
Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.
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Affiliation(s)
- Harinakshi Sanikini
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands; Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Team, Villejuif, Paris, France; Univ Paris Sud, UMRS 1018, Villejuif, Paris, France
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Duell EJ, Bonet C, Muñoz X, Lujan-Barroso L, Weiderpass E, Boutron-Ruault MC, Racine A, Severi G, Canzian F, Rizzato C, Boeing H, Overvad K, Tjønneland A, Argüelles M, Sánchez-Cantalejo E, Chamosa S, Huerta JM, Barricarte A, Khaw KT, Wareham N, Travis RC, Trichopoulou A, Trichopoulos D, Yiannakouris N, Palli D, Agnoli C, Tumino R, Naccarati A, Panico S, Bueno-de-Mesquita HB, Siersema PD, Peeters PHM, Ohlsson B, Lindkvist B, Johansson I, Ye W, Johansson M, Fenger C, Riboli E, Sala N, González CA. Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population. Int J Cancer 2015; 136:880-93. [PMID: 24947433 DOI: 10.1002/ijc.29034] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Accepted: 05/16/2014] [Indexed: 12/12/2022]
Abstract
ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.
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Affiliation(s)
- Eric J Duell
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
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Beltrán-Anaya FO, Poblete TM, Román-Román A, Reyes S, de Sampedro J, Peralta-Zaragoza O, Rodríguez MÁ, del Moral-Hernández O, Illades-Aguiar B, Fernández-Tilapa G. The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population. BMC Gastroenterol 2014; 14:223. [PMID: 25539656 PMCID: PMC4302603 DOI: 10.1186/s12876-014-0223-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 12/17/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer. METHODS A total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3' variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer. RESULTS H. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3-15.1; p < 0.001) and gastric cancer (OR = 5.9, 95% CI = 1.5-22.1) were significantly increased in individuals who harbored the EPIYA-ABCC cagA gene pattern. CONCLUSIONS cagA-positive H. pylori is highly prevalent in southern Mexico, and all CagA variants were of the western type. The cagA alleles that code for EPIYA-ABCC motif patterns are associated with peptic ulcers and gastric cancer.
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Radić M. Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases. World J Gastroenterol 2014; 20:12839-12846. [PMID: 25278681 PMCID: PMC4177466 DOI: 10.3748/wjg.v20.i36.12839] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Accepted: 07/22/2014] [Indexed: 02/06/2023] Open
Abstract
The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori (H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords “rheumatoid arthritis”, “Sjögren’s syndrome”, “systemic sclerosis”, “systemic lupus erythematosus”, “Helicobacter pylori” and “pathogenesis”. A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article I review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.
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Katra R, Kabelka Z, Jurovcik M, Hradsky O, Kraus J, Pavlik E, Nartova E, Lukes P, Astl J. Pilot study: Association between Helicobacter pylori in adenoid hyperplasia and reflux episodes detected by multiple intraluminal impedance in children. Int J Pediatr Otorhinolaryngol 2014; 78:1243-9. [PMID: 24865809 DOI: 10.1016/j.ijporl.2014.04.040] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 04/18/2014] [Accepted: 04/20/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVES The aim of this pilot study was to investigate an association between laryngopharyngeal reflux detected by combined multiple intraluminal impedance and pH monitoring and Helicobacter pylori in adenoid hyperplasia detected with real time polymerase chain reaction (PCR). METHODS The study group consisted of 30 children (median age 5.34 years) with extraesophageal symptoms of gastroesophageal reflux disease with adenoid hyperplasia. All children underwent adenoidectomy with subsequent PCR detection of H. pylori DNA in the tissue and multiple intraluminal impedance and pH monitoring. The most proximal impedance sensor was located 1cm caudal to the entrance of the oesophagus. RESULTS We found significant differences in the number of reflux episodes among patients with PCR positivity (median 35) and negativity (median 0) of H. pylori (p-value of Mann-Whitney U-test 0.0056). Patients with PCR positivity of H. pylori had significantly more reflux episodes reaching the upper oesophageal sphincter (p-value of Mann-Whitney U-test 0.023). The absence of reflux episode was the only independent factor for PCR negativity of H. pylori in the multiple logistic regression model. CONCLUSIONS These results support the hypothesis that reflux episodes reaching the upper oesophageal sphincter may play an important role in the transmission of H. pylori into lymphoid tissue of the nasopharynx and thus may contribute to adenoid hyperplasia in children.
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Affiliation(s)
- R Katra
- Department of ENT, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic.
| | - Z Kabelka
- Department of ENT, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
| | - M Jurovcik
- Department of ENT, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
| | - O Hradsky
- Department of Paediatrics, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
| | - J Kraus
- Department of Otorhinolaryngology, Hospital Rudolph and Stephanie, Benešov, Czech Republic
| | - E Pavlik
- Department of Microbiology and Immunology and Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, General Faculty Hospital, Charles University, Prague, Czech Republic
| | - E Nartova
- Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
| | - P Lukes
- Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic
| | - J Astl
- Department of ENT, 3rd Faculty of Medicine, Charles University, Military University Hospital, Prague, Czech Republic
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Abstract
BACKGROUND Gastric cancer is the second most common cause of cancer deaths worldwide. The vast majority of gastric cancers are inflammation-related cancers caused by infection with Helicobacter pylori. H. pylori-induced oxidative stress damages DNA, resulting in genetic instability. In addition, H. pylori itself can cause DNA damage and epigenetic changes that trigger genetic instability and neoplastic transformation. SUMMARY H. pylori strain-specific components act in combination with host factors and environmental and dietary factors to greatly enhance the inflammatory response and thus the cancer risk. Variations in several key factors, such as the cag pathogenicity island and the VacA protein, can trigger a greater inflammatory response in host cells. Genetic polymorphisms in the host such as in the IL-1β gene, and chromosomes 9p21.3 and 10q23 also play a contributing role. Finally, diet is a major external factor that modulates the risk of gastric cancer. KEY MESSAGE The majority of gastric cancers are inflammation-related cancers caused by infection with H. pylori. Eradication of H. pylori is important for the prevention and treatment of gastric cancer. PRACTICAL IMPLICATIONS H. pylori eradication results in healing of gastritis and prevention of further H. pylori-induced genetic damage. Eradication of H. pylori prior to development of atrophic gastritis can prevent the development of gastric cancer. Japan has undertaken a nationwide program to identify and eliminate H. pylori, along with surveillance for those who underwent H. pylori eradication too late to eliminate cancer risk. Population-wide eradication of H. pylori will result in gastric cancer becoming a vanishingly rare disease.
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Affiliation(s)
- Wei Zhang
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VAMC and Baylor College of Medicine, Houston, Tex., USA
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Companioni O, Bonet C, Muñoz X, Weiderpass E, Panico S, Tumino R, Palli D, Agnoli C, Vineis P, Boutron-Ruault MC, Racine A, Clavel-Chapelon F, Travis RC, Khaw KT, Riboli E, Murphy N, Vergnaud AC, Trichopoulou A, Benetou V, Trichopoulos D, Lund E, Johansen D, Lindkvist B, Johansson M, Sund M, Ardanaz E, Sánchez-Cantalejo E, Huerta JM, Dorronsoro M, Ramón Quirós J, Tjonneland A, Mortensen LM, Overvad K, Chang-Claude J, Rizzato C, Boeing H, Bueno-de-Mesquita HB, Bueno de Mesquita HB, Siersema P, Peeters PHM, Numans ME, Carneiro F, Licaj I, Freisling H, Sala N, González CA. Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort. Int J Cancer 2014; 134:92-101. [PMID: 23824692 DOI: 10.1002/ijc.28357] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 04/16/2013] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.
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Affiliation(s)
- Osmel Companioni
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, Barcelona, 08908, Spain
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Duell EJ, Lujan-Barroso L, Llivina C, Muñoz X, Jenab M, Boutron-Ruault MC, Clavel-Chapelon F, Racine A, Boeing H, Buijsse B, Canzian F, Johnson T, Dalgård C, Overvad K, Tjønneland A, Olsen A, Sánchez SC, Sánchez-Cantalejo E, Huerta JM, Ardanaz E, Dorronsoro M, Khaw KT, Travis RC, Trichopoulou A, Trichopoulos D, Rafnsson S, Palli D, Sacerdote C, Tumino R, Panico S, Grioni S, Bueno-de-Mesquita HB, Ros MM, Numans ME, Peeters PH, Johansen D, Lindkvist B, Johansson M, Johansson I, Skeie G, Weiderpass E, Duarte-Salles T, Stenling R, Riboli E, Sala N, González CA. Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. GENES AND NUTRITION 2013; 8:549-60. [PMID: 23737080 DOI: 10.1007/s12263-013-0346-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Accepted: 05/07/2013] [Indexed: 01/12/2023]
Abstract
Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.
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Affiliation(s)
- Eric J Duell
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, alan Institute of Oncology (ICO), Avda Gran Via 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Spain,
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Determination of Helicobacter pylori Virulence Genes in Gastric Biopsies by PCR. ISRN GASTROENTEROLOGY 2013; 2013:606258. [PMID: 23691338 PMCID: PMC3649278 DOI: 10.1155/2013/606258] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/24/2013] [Accepted: 03/25/2013] [Indexed: 12/14/2022]
Abstract
Aim. The aim of this study was to identify the presence of H. pylori in biopsy specimens from symptomatic patients by PCR. In addition, the rate of cagA, vacA, iceA1, and iceA2 virulence genes was determined. Materials and Methods. One hundred antral gastric biopsy specimens were collected during endoscopy from patients suffering from gastroduodenal symptoms. The samples were collected by the gastroenterologists in their own clinics in Ramallah, Palestine. DNA was extracted from the biopsies and subsequently used for PCR identification of H. pylori and the virulence genes using specific primers. Results. The rate of positive H. pylori in the collected biopsies was 44%. The rates of the virulence genes in this sample: cagA, vacA, iceA1, and iceA2 were 65.9%, 40.9%, 63.6%, and 84.1%, respectively. Conclusion. The iceA2 gene was the most frequent in this study. Much research is necessary to determine the presence of an association of this gene with gastric pathology. Variation in the rates of the iceA gene in different countries is a strong indication of its geographical distribution. This study would provide important information regarding the prevalence of virulence genes (vacA, cagA, iceA1, and iceA2) in H. pylori strains in the sample tested in this country.
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Bertuccio P, Rosato V, Andreano A, Ferraroni M, Decarli A, Edefonti V, La Vecchia C. Dietary patterns and gastric cancer risk: a systematic review and meta-analysis. Ann Oncol 2013; 24:1450-8. [PMID: 23524862 DOI: 10.1093/annonc/mdt108] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Declines in gastric cancer (GC) incidence and mortality have been related to improvements in diet. It is therefore important to consider dietary patterns. DESIGN We conducted a systematic review and meta-analysis of the literature through Medline and Embase databases. RESULTS We identified 16 papers, of these 9 derived dietary patterns through an a posteriori method, 5 through a priori scores, and 2 used both approaches. Eight studies that used the a posteriori approach were considered for the meta-analysis. A favorable role on GC emerged for the 'Prudent/healthy', with an odds ratio (OR) of 0.75 [95% confidence interval (CI): 0.63-0.90], for the highest versus the lowest category. Similar results emerged for separate anatomical subtypes. An unfavorable role on GC emerged for the 'Western/unhealthy' dietary pattern, with an OR of 1.51 (95% CI: 1.21-1.89). This association was weaker for the distal/NOS (not otherwise specified) category (OR = 1.36) compared with the cardia GC (OR = 2.05). Among the a priori scores, the ORs ranged from 0.2 to 0.7 for the favorable and from 1.8 to 6.9 for the unfavorable ones. CONCLUSION There is a ~2-fold difference in GC risk between a 'Prudent/healthy' diet-rich in fruits and vegetables, and a 'Western/unhealthy' diet-rich in starchy foods, meat and fats.
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Affiliation(s)
- P Bertuccio
- Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy.
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Carneiro F, Lauwers GY. Epithelial Tumours of the Stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2013:180-222. [DOI: 10.1002/9781118399668.ch13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Endocarditis and risk of cancer: a Danish nationwide cohort study. Am J Med 2013; 126:58-67. [PMID: 23260503 DOI: 10.1016/j.amjmed.2012.07.026] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2012] [Revised: 07/12/2012] [Accepted: 07/12/2012] [Indexed: 01/11/2023]
Abstract
BACKGROUND Endocarditis may be a marker for bacteremia-associated occult cancer. Intensive antibiotic treatment in endocarditis is suggested to reduce long-term cancer risk. We examined these hypotheses in a nationwide cohort study. METHODS Endocarditis patients and cancer cases were identified from the Danish National Registry of Patients and the Danish Cancer Registry during 1978-2008. We compared the incidences of various cancers among study subjects to expected incidences based on national age-, sex-, and site-specific rates. RESULTS We observed 997 cancers among 8445 endocarditis patients (median follow-up of 3.5 years), reflecting an increased standardized incidence rate (SIR) of 1.61 (95% confidence interval [CI], 1.51-1.71). Cancer risk was highly elevated during the first 3 months of follow-up (SIR=8.03; 95% CI, 6.92-9.26), partly due to a 15- to 30-fold increased risk of hematological or liver cancers. Between 3-month and 5-year follow-ups, cancer incidence remained 1.5-fold higher than expected, including 2- and 4-fold increased SIRs for colorectal and liver cancers, respectively. Beyond 5 years of observation, the overall cancer SIR was 1.21 (95% CI, 1.10-1.34). Long-term associations were weak for several cancers hypothesized to be associated with antibiotic use, including prostate, gastric, and breast cancer. CONCLUSION Endocarditis is a substantial clinical marker for presence of occult cancer. We found no evidence of decreased long-term cancer risk after antibiotic treatment for endocarditis.
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Haneda M, Kato M, Ishigaki S, Suzuki M, Takahashi M, Nakagawa M, Ono S, Mori Y, Mabe K, Nakagawa S, Kudo T, Shimizu Y, Asaka M. Identification of a high risk gastric cancer group using serum pepsinogen after successful eradication of Helicobacter pylori. J Gastroenterol Hepatol 2013; 28:78-83. [PMID: 23034090 DOI: 10.1111/j.1440-1746.2012.07285.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/08/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Pepsinogen (PG) method is widely used to identify high risk groups of gastric cancer. It is very useful before Helicobacter pylori eradication, but after eradication the method becomes useless because the PGI, PGII, PGI/II ratios change. Therefore, we aimed to identify a high risk group for gastric cancer using serum pepsinogen after successful eradication of H. pylori. METHODS A total of 261 participants were enrolled after successful eradication of H. pylori in Hokkaido University Hospital from 1995 to 2010. Participants with renal failure, taking proton pump inhibitors, and those with advanced gastric cancer were excluded. Serum levels of PGI and II were measured using chemiluminescent immunoassay method. RESULTS Receiver operating characteristic curves using cancerous and non-cancerous data in post-eradication determined the optimal cut-off value of PGI/II as 4.5. The sensitivity and the specificity were 65.9% and 79.3%, respectively. The usual PG method includes 48.9% of cancer cases, and the PGI/II ≤ 4.5 in post-eradication includes 65.9% of them, and it includes approximately half of the high risk group of diffuse type cancer. PGI/II ≤ 4.5 in post-eradication included many gastric cancer cases detected after eradication (12/16 = 75%). CONCLUSION In the identification of a high risk group for gastric cancer, we suggest that the optimal cut-off value of PGI/II after successful eradication of H. pylori is 4.5. PGI/II ≤ 4.5 in post-eradication includes more gastric cancer cases compared with the traditional PG method, and 75% of gastric cancer cases detected after eradication.
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Affiliation(s)
- Masahira Haneda
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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García-González MA, Quintero E, Bujanda L, Nicolás D, Benito R, Strunk M, Santolaria S, Sopeña F, Badía M, Hijona E, Pérez-Aísa MA, Méndez-Sánchez IM, Thomson C, Carrera P, Piazuelo E, Jiménez P, Espinel J, Campo R, Manzano M, Geijo F, Pellisé M, González-Huix F, Espinós J, Titó L, Zaballa M, Pazo R, Lanas A. Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype. Mutagenesis 2012; 27:771-777. [PMID: 22952149 DOI: 10.1093/mutage/ges049] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.
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Alfizah H, Ramelah M, Rizal AM, Anwar AS, Isa MR. Association of Malaysian Helicobacter pylori virulence polymorphisms with severity of gastritis and patients' ethnicity. Helicobacter 2012; 17:340-9. [PMID: 22967117 DOI: 10.1111/j.1523-5378.2012.00956.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Polymorphisms of Helicobacter pylori cagA and vacA genes do exist and may contribute to differences in H. pylori infection and gastroduodenal diseases among races in the Malaysian population. This study was conducted to characterize the polymorphisms in H. pylori cagA and vacA in Malaysian population. METHODS A total of 110 H. pylori isolates were genotyped by PCR and sequenced for cagA and PCR-RFLP for vacA. RESULTS East Asian cagA was predominantly detected (64.5%), whereas vacA s1m1 and s1m2 alleles were detected in 60.9 and 37.3% of strains, respectively. A statistical association between cagA type with patients' ethnicity (p < .0001) and age group >50 years old (p = .027) was identified. vacA alleles showed significant association with age group >50 years old (p = .017) and increased neutrophil activity in gastric mucosa (p = .028 and p = .016 for moderate and marked activity, respectively). Further identification of vacA polymorphism revealed that 84% of strains from Malays and Indians showed one RFLP pattern (RFLP-1), whereas more than one RFLP patterns (RFLP-2, 3, 4, 5, 6, and 8) were predominantly observed in strains from Chinese (82%) (p < .0001). Increasing severity of gastric inflammation was observed in gastric mucosa infected with strains carrying RFLP-2, 3, 4, 5, and 6 (p = .037). About 86.6% of H. pylori strains with East Asian cagA were vacA RFLP-2, 3, 4, 5, 6, and 8, and 88% of Western cagA strains were vacA RFLP-1 (p < .0001). Chinese and Indians are susceptible to different virulence genotypes of H. pylori, whereas Malays showed a mixed virulence genotypes. CONCLUSION Marked differences in the polymorphisms of cagA and vacA were observed among strains in Malaysian population. This provides a new insight into the pathogenicity of H. pylori in multiracial population.
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Affiliation(s)
- Hanafiah Alfizah
- Department of Medical Microbiology & Immunology, National University of Malaysia, Cheras, Kuala Lumpur, Malaysia.
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