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Kim HJ, Kim N, Jang JY, Kim S, Lee J, Oh HJ. Influence of Cytokine Genetic Polymorphisms in Helicobacter pylori-Associated Gastric Inflammation According to Sex in South Korea. Gut Liver 2024; 18:1002-1013. [PMID: 38388182 PMCID: PMC11565013 DOI: 10.5009/gnl230359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 12/20/2023] [Accepted: 12/25/2023] [Indexed: 02/24/2024] Open
Abstract
Background/Aims : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex. Methods : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor (TGF)-B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system. Results : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227). Conclusions : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.
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Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea
| | - Sihyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jongchan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyeon Jeong Oh
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
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Hnatyszyn A, Szalata M, Zielińska A, Wielgus K, Danielewski M, Hnatyszyn PT, Pławski A, Walkowiak J, Słomski R. Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer. Hered Cancer Clin Pract 2024; 22:9. [PMID: 38867324 PMCID: PMC11167877 DOI: 10.1186/s13053-024-00282-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 06/04/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments. METHODS Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients. RESULTS Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene. CONCLUSIONS The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer.
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Affiliation(s)
- Andrzej Hnatyszyn
- Independent Public Health Care Centre in Nowa Sol, Multispecialty Hospital, Chalubinskiego 7, Nowa Sol, 67-100, Poland
| | - Marlena Szalata
- Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Dojazd 11, Poznań, 60-632, Poland
| | - Aleksandra Zielińska
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants National Research Institute, Wojska Polskiego 71B, Poznań, 60-630, Poland
| | - Karolina Wielgus
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | - Mikołaj Danielewski
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | | | - Andrzej Pławski
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, 60-479, Poland
- Department of General, Endocrinological Surgery and Gastrointestinal Oncology, Institute of Surgery, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznań, 60-355, Poland
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, Poznań, 60-572, Poland
| | - Ryszard Słomski
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants National Research Institute, Wojska Polskiego 71B, Poznań, 60-630, Poland.
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, 60-479, Poland.
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Jacob J, Millien V, Berger S, Hernaez R, Ketwaroo GA, Flores AG, Hou JK, Jarbrink-Sehgal ME, Khalaf NI, Rosen DG, El-Serag HB, Tan MC. Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution. J Clin Gastroenterol 2024; 58:432-439. [PMID: 37436841 PMCID: PMC10787041 DOI: 10.1097/mcg.0000000000001890] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 06/12/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. METHODS This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. RESULTS In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. CONCLUSIONS GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.
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Affiliation(s)
- Jake Jacob
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | | | - Scott Berger
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Ruben Hernaez
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Department of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Gyanprakash A. Ketwaroo
- Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Avegail G. Flores
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Department of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Jason K. Hou
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Department of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | | | - Natalia I. Khalaf
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Department of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Daniel G. Rosen
- Department of Pathology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Hashem B. El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Mimi C. Tan
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Department of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
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Wang L, Xiao S, Zheng Y, Gao Z, Fan F. Impact of interaction between interleukin-6 gene polymorphism and Helicobacter pylori infection on susceptibility to gastric cancer. Eur J Cancer Prev 2024; 33:136-140. [PMID: 37669156 DOI: 10.1097/cej.0000000000000835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
OBJECTIVE This study aimed to evaluate the association between four single nucleotide polymorphisms (SNPs) of the interleukin-6 (IL-6) gene and gastric cancer (GC), and impact of interaction between IL-6 SNPs and Helicobacter pylori (H. pylori ) infection on susceptibility to GC. METHODS Logistic regression was used to test the relationships between four SNPs of IL-6 gene and GC susceptibility. A generalized multifactor dimensionality reduction (GMDR) model was employed to assess the interaction effect between IL-6 gene and H. pylori infection on GC risk. RESULTS Logistic regression analysis indicated that the rs1800795-C allele was associated with increased GC risk, adjusted ORs (95% CI) were 1.80 (1.21-2.41) (CC vs. GG) and 1.68 (1.09-2.30) (C vs. G), respectively. The rs10499563-C allele was associated with decreased risk of GC, and adjusted ORs (95% CI) were 0.62 (0.31-0.93) (TC vs. TT), 0.52 (0.18-0.89) (CC vs. TT) and 0.60 (0.29-0.92) (C vs. T), respectively. GMDR methods found a two-dimensional model combination (including rs1800795 and H. pylori infection) was statistically significant. The selected model had testing balanced accuracy of 59.85% and the best cross-validation consistencies of 10/10 ( P = 0.0107). Compared with H. pylori -negative subjects with rs1800795- GG genotype, H. pylori -positive participants with GC or CC genotype had the highest risk of GC, the OR (95% CI) was 3.34 (1.78-4.97). CONCLUSION The rs1800795-C allele was associated with increased GC risk and the rs10499563-C allele was associated with decreased GC risk. The interaction between rs1800795 and H. pylori infection was also correlated with increased risk of GC.
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Affiliation(s)
- Longyue Wang
- Department of Hepatobiliary, pancreatic and gastric surgery, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University
| | - Shuaishuai Xiao
- Department of Hepatobiliary, pancreatic and gastric surgery, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University
| | - Yiming Zheng
- Department of Hepatobiliary, pancreatic and gastric surgery, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University
| | - Zefeng Gao
- Department of Hepatobiliary, pancreatic and gastric surgery, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University
| | - Fan Fan
- Department of Gastroenterology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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Singh RD, Dholariya S, Shekher A, Avadhesh, Parchwani D, Gupta SC. Role of IL-1 gene polymorphisms in common solid cancers. MULTIFACETED ROLE OF IL-1 IN CANCER AND INFLAMMATION 2023:1-69. [DOI: 10.1016/b978-0-12-824273-5.00002-7] [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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Backert S, Linz B, Tegtmeyer N. Helicobacter pylori-Induced Host Cell DNA Damage and Genetics of Gastric Cancer Development. Curr Top Microbiol Immunol 2023; 444:185-206. [PMID: 38231219 DOI: 10.1007/978-3-031-47331-9_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Gastric cancer is a very serious and deadly disease worldwide with about one million new cases every year. Most gastric cancer subtypes are associated with genetic and epigenetic aberrations caused by chromosome instability, microsatellite instability or Epstein-Barr virus infection. Another risk factor is an infection with Helicobacter pylori, which also triggers severe alterations in the host genome. This pathogen expresses an extraordinary repertoire of virulence determinants that take over control of important host cell signaling functions. In fact, H. pylori is a paradigm of persistent infection, chronic inflammation and cellular destruction. In particular, H. pylori profoundly induces chromosomal DNA damage by introducing double-strand breaks (DSBs) followed by genomic instability. DSBs appear in response to oxidative stress and pro-inflammatory transcription during the S-phase of the epithelial cell cycle, which mainly depends on the presence of the bacterial cag pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). This scenario is closely connected with the T4SS-mediated injection of ADP-glycero-β-D-manno-heptose (ADP-heptose) and oncoprotein CagA. While ADP-heptose links transcription factor NF-κB-induced innate immune signaling with RNA-loop-mediated DNA replication stress and introduction of DSBs, intracellular CagA targets the tumor suppressor BRCA1. The latter scenario promotes BRCAness, a disease characterized by the deficiency of effective DSB repair. In addition, genetic studies of patients demonstrated the presence of gastric cancer-associated single nucleotide polymorphisms (SNPs) in immune-regulatory and other genes as well as specific pathogenic germline variants in several crucial genes involved in homologous recombination and DNA repair, all of which are connected to H. pylori infection. Here we review the molecular mechanisms leading to chromosomal DNA damage and specific genetic aberrations in the presence or absence of H. pylori infection, and discuss their importance in gastric carcinogenesis.
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Affiliation(s)
- Steffen Backert
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
| | - Bodo Linz
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany
| | - Nicole Tegtmeyer
- Division of Microbiology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058, Erlangen, Germany.
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Wang S, Zhang M, Yu L, Tian F, Lu W, Wang G, Chen W, Wang J, Zhai Q. Evaluation of the Potential Protective Effects of Lactobacillus Strains against Helicobacter pylori Infection: A Randomized, Double-Blinded, Placebo-Controlled Trial. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2022; 2022:6432750. [PMID: 36193094 PMCID: PMC9525740 DOI: 10.1155/2022/6432750] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 08/23/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND The beneficial effects of probiotic supplementation standard antibiotic therapies for Helicobacter pylori infection have been verified, but the ability of probiotic monotherapy to eradicate H. pylori remains unclear. AIM To evaluate the accuracy and efficacy of specific Lactobacillus strains against H. pylori infection. METHODS Seventy-eight patients with H. pylori infection were treated with strain L. crispatus G14-5M (L. crispatus CCFM1118) or L. helveticus M2-09-R02-S146 (L. helveticus CCFM1121) or L. plantarum CCFM8610 at a dose of 2 g twice daily for one month. 14C-urea breath test, the gastrointestinal symptom rating scale, serum pepsinogen concentrations, and serum cytokine concentrations of patients were measured at baseline and end-of-trial to analyze the effect of the Lactobacillus strains in eradicating H. pylori infection and reducing gastrointestinal discomfort in patients. In addition, the composition and abundance of the intestinal microbiota of patients were also measured at end-of-trial. RESULTS The 14C-urea breath test value of the three Lactobacillus treatment groups had decreased significantly, and the eradication rate of H. pylori had increased by the end of the trial. In particular, the eradication rate in the G14-5M treatment group was significantly higher than the placebo group (70.59% vs. 15.38%, P=0.0039), indicating that one-month administration of the G14-5M regimen was sufficient to eradicate H. pylori infection. The ingestion of Lactobacillus strains also ameliorated the gastrointestinal symptom rating scale scores, and the serum interleukin-8 concentrations of H. pylori-infected patients appeared to modulate the gut microbiota of patients. However, none of the Lactobacillus strains had a significant effect on general blood physiological characteristics, serum tumor necrosis factor α concentrations, or serum pepsinogen concentrations in the patients. CONCLUSION Three Lactobacillus strains significantly alleviate the gastrointestinal discomfort and the gastric inflammatory response of H. pylori-infected patients. The activity of probiotics in eradicating H. pyloriinfection may be species/strain specific.
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Affiliation(s)
- Shumin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Meiyi Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jialin Wang
- Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
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The role of non-Helicobacter pylori bacteria in the pathogenesis of gastroduodenal diseases. Gut Pathog 2022; 14:19. [PMID: 35606878 PMCID: PMC9125830 DOI: 10.1186/s13099-022-00494-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 05/04/2022] [Indexed: 02/06/2023] Open
Abstract
Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship.
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Xing Y, Chen H, Guo Z, Zhou X. Circular RNA circ0007360 Attenuates Gastric Cancer Progression by Altering the miR-762/IRF7 Axis. Front Cell Dev Biol 2022; 10:789073. [PMID: 35252169 PMCID: PMC8891931 DOI: 10.3389/fcell.2022.789073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/25/2022] [Indexed: 11/23/2022] Open
Abstract
Gastric cancer is a major health burden worldwide. Circular RNAs (circRNAs) are a novel family of noncoding RNAs that are involved in multiple types of cancers, including gastric cancer. As biological functions and the underlying molecular mechanisms of the newly identified circRNA circ0007360 have not been investigated, our present study focused on the role of circ0007360 in the progression of gastric cancer. After characterizing circ0007360 as a cytoplasmic circRNA, we revealed the inhibitory effects of circ0007260 on the survival, migration, invasion, and stemness of gastric cancer cells. Subsequently, miR-762 was identified as a direct target microRNA (miRNA) of circ0007360 and was proved to act as a vital downstream transcript to fulfill the tumor-promoting effects in the absence of circ0007360. Furthermore, we demonstrated that interferon regulatory factor 7 (IRF7), which was validated as a target gene of miR-762, serves as an indirect target of circ0007360 to attenuate the progression of gastric cancer. Moreover, in vivo experiments confirmed the potentiation of gastric cancer cell growth and stemness upon depletion of circ0007360. In summary, our results revealed that activation of the circ0007360/miR-762/IRF7 axis is a novel mechanism for the attenuation of gastric cancer progression. Our study unveils the diagnostic and therapeutic values of circ0007360 in patients with gastric cancer.
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Affiliation(s)
- Yawei Xing
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongxia Chen
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zixiang Guo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaodong Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Xiaodong Zhou,
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Abstract
Helicobacter pylori is the most prevalent infection worldwide, while non-alcoholic fatty liver disease emerged as the most frequent liver disease. The common occurrence can be either by chance or due to certain pathogenetic factors. Epidemiologic studies revealed that the risk of non-alcoholic liver disease is increased in patients infected with Helicobacter pylori. DNA fragments of Helicobacter pylori were rarely identified in human samples of liver carcinoma and fatty liver. Helicobacter pylori could influence the development of non-alcoholic fatty liver either by hormonal (ghrelin? gastrin? insulin?), or by effect of pro-inflammatory cytokines (interleukin 1 and 8, tumor necrosis factor ɑ, interferon ɣ) and by changes of gut microbiome as well. Probiotic supplementation could improve some clinical parameters of non-alcoholic fatty liver disease and eradication rates of Helicobacter pylori. Regimens used for eradication can be safely administered, although non-alcoholic fatty liver increases the risk of drug-induced liver damage. Controlled studies of the effect of eradication on the development and progression of non-alcoholic fatty liver are warranted.
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Affiliation(s)
- György M Buzás
- Department of Gastroenterology, Ferencváros Health Center, Budapest, Hungary -
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Pereira-Marques J, Ferreira RM, Machado JC, Figueiredo C. The influence of the gastric microbiota in gastric cancer development. Best Pract Res Clin Gastroenterol 2021; 50-51:101734. [PMID: 33975676 DOI: 10.1016/j.bpg.2021.101734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/12/2021] [Accepted: 02/15/2021] [Indexed: 01/31/2023]
Abstract
Colonization of the stomach by Helicobacter pylori is the trigger for a series of gastric mucosal changes that culminate in gastric cancer. Infection with this bacterium is considered the major risk factor for this malignancy. The introduction of high-throughput sequencing technologies coupled to advanced computational pipelines offered an improved understanding of the microbiome, and it is now currently accepted that, besides H. pylori, the stomach harbours a complex microbial community. While it is well established that H. pylori plays a central role in gastric carcinogenesis, the significance of the non-H. pylori microbiota is yet to be clarified. This review will address the state of the art on the relationship between the gastric microbiota and gastric cancer development, and identify areas where additional research is needed before translating microbiome research into preventive and therapeutic strategies to reduce gastric cancer burden.
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Affiliation(s)
- Joana Pereira-Marques
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
| | - Rui M Ferreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
| | - Jose C Machado
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal; Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200 - 319, Porto, Portugal.
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal; Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200 - 319, Porto, Portugal.
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12
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Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution. Microorganisms 2021; 9:microorganisms9020240. [PMID: 33503840 PMCID: PMC7912213 DOI: 10.3390/microorganisms9020240] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/20/2021] [Accepted: 01/21/2021] [Indexed: 12/27/2022] Open
Abstract
The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.
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13
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TNF genetic polymorphism (rs1799964) may modify the effect of the dietary inflammatory index on gastric cancer in a case-control study. Sci Rep 2020; 10:14590. [PMID: 32883994 PMCID: PMC7471946 DOI: 10.1038/s41598-020-71433-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/22/2020] [Indexed: 12/26/2022] Open
Abstract
The inflammatory process is known to increase the risk of gastric carcinogenesis, and both genetic and dietary factors are associated with inflammation. In the present study of 1,125 participants (373 cases and 752 controls), we determined whether the dietary inflammatory index (DII) is associated with the risk of gastric cancer (GC) and investigated whether a TNF polymorphism (rs1799964) modifies this association. Semi-quantitative food frequency questionnaire derived data were used to calculate the DII scores. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic models adjusted for confounders. When we stratified the data by sex, the association between GC and the DII was significant only among the women (OR, 2.27; 95% CI 1.25-4.19), and the DII effect on the risk of GC differed depending on the TNF genotype (OR, 2.30; 95% CI 1.27-4.24 in TT genotype; OR, 0.78; 95% CI 0.37-1.65 in CC + CT, p for interaction = 0.035). Furthermore, the association between the DII and GC was significant in the Helicobacter pylori-positive group; similarly, the effect differed based on the TNF genotype (OR, 1.76; 95% CI 1.13-2.73 in TT genotype; OR,0.98; 95% CI 0.54-1.77 in CT + CC, p for interaction = 0.034). In conclusion, rs1799964 may modify the effect of the DII on GC.
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14
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Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, Limarzi F, Ferro J, Parente P, Fassan M. Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes. Pathologica 2020; 112:166-185. [PMID: 33179620 PMCID: PMC7931572 DOI: 10.32074/1591-951x-166] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer accounts for about 6% of cancers worldwide, being the fifth most frequently diagnosed malignancy and the third leading cause of cancer related death. Gastric carcinogenesis is a multistep and multifactorial process and is the result of the complex interplay between genetic susceptibility and environmental factors. The identification of predisposing conditions and of precancerous lesions is the basis for screening programs and early stage treatment. Furthermore, although most gastric cancers are sporadic, familial clustering is observed in up to 10% of patients. Among them, hereditary cases, related to known cancer susceptibility syndromes and/or genetic causes are thought to account for 1-3% of all gastric cancers. The pathology report of gastric resections specimens therefore requires a standardized approach as well as in depth knowledge of prognostic and treatment associated factors.
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Affiliation(s)
- Irene Gullo
- Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ) & Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal and Instituto de Investigação e Inovação em Saúde (i3S) & Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Portugal
| | - Federica Grillo
- Correspondence Federica Grillo Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova and Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy, largo Rosanna Benzi 10, 16132 Genova, Italy Tel. +39 010 5555957 Fax: +39 010 5556392 E-mail:
| | | | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Fatima Carneiro
- Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ) & Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal and Instituto de Investigação e Inovação em Saúde (i3S) & Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Portugal
| | - Luca Saragoni
- UO Anatomia Patologica, Ospedale G.B. Morgagni-L. Pierantoni, Forlì, Italy
| | - Francesco Limarzi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST/IRCCS), Meldola (FC), Italy
| | - Jacopo Ferro
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG) Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Italy
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15
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de Almeida NM, Fernandes A, Romãozinho JM, Freire P, Donato MM, Cardoso O, Luxo C, Cipriano MA, Marinho C, Calhau C, Figueiredo P. Correlation of
NOD2
genotypes with
Helicobacter pylori
infection in a
South‐European
country. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Nuno Miguel de Almeida
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | | | - José Manuel Romãozinho
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Paulo Freire
- Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Maria M. Donato
- CIMAGO, Faculty of Medicine University of Coimbra Coimbra Portugal
| | - Olga Cardoso
- Laboratory of Microbiology, Faculty of Pharmacy University of Coimbra Coimbra Portugal
- CIEPQPF, Faculty of Sciences and Technology University of Coimbra Coimbra Portugal
| | - Cristina Luxo
- Laboratory of Microbiology, Faculty of Pharmacy University of Coimbra Coimbra Portugal
- CIEPQPF, Faculty of Sciences and Technology University of Coimbra Coimbra Portugal
| | | | - Carol Marinho
- Pathology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
| | - Carlos Calhau
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
| | - Pedro Figueiredo
- Gastroenterology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal
- Faculty of Medicine University of Coimbra Coimbra Portugal
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16
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Bakhti SZ, Latifi-Navid S, Safaralizadeh R. Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects. Cancer Med 2020; 9:4808-4822. [PMID: 32363738 PMCID: PMC7333836 DOI: 10.1002/cam4.3068] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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17
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Fiorini G, Saracino IM, Zullo A, Pavoni M, Saccomanno L, Lazzarotto T, Cavallo R, Antonelli G, Vaira B. Antibiotic Resistance and Therapy for H. pylori Infection in Immigrant Patients Treated in Italy. J Clin Med 2020; 9:jcm9051299. [PMID: 32370005 PMCID: PMC7288298 DOI: 10.3390/jcm9051299] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/27/2020] [Accepted: 04/29/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Helicobacter pylori (H. pylori) infection is the leading cause of both peptic ulcers and gastric tumors, including low-grade MALT-lymphoma and adenocarcinoma. Although it is decreasing in developed countries, H. pylori prevalence remains high in developing areas, mainly due to low socio-economic levels, and the potential consumption of contaminated water. Moreover, a different pattern of primary antibiotic resistance is expected in their H. pylori isolates, potentially affecting the efficacy of standard eradication therapies. Indeed, a previous study showed the eradication rate following triple therapy was distinctly lower in dyspeptic H. pylori infected immigrants living in Italy as compared to Italian patients. Aims: to evaluate the resistance pattern in H. pylori isolates from immigrant patients in Italy, and the success rate of first-line therapy in these patients. Materials and Methods: This retrospective study evaluated data of consecutive immigrant patients, diagnosed with H. pylori infection in a single center (Bologna, Italy) between January 2009 and January 2019. Patients underwent first-line therapy with either sequential or Pylera® (Allergan USA, Inc. Madison, NJ, USA) therapy. Results: A total of 609 immigrants were diagnosed with H. pylori infection during the study period, but 264 previously received an eradication therapy. Therefore, the study was focused on 294 out of 345 naïve patients with a successful bacterial culture with antibiogram. Latin America immigrants had the highest overall resistance rate. Levofloxacin resistance rate was significantly higher in Latin Americans and Asians as compared with Europeans. Based on resistance patterns, sequential therapy showed a clear decreasing trend in eradication rates. Conclusions: while antibiotic resistance rates are generally increasing worldwide, Pylera® seems to achieve a good performance as first-line treatment in all naïve foreigner patients, except for Africans.
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Affiliation(s)
- Giulia Fiorini
- Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy; (G.F.); (I.M.S.); (M.P.); (L.S.)
| | - Ilaria Maria Saracino
- Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy; (G.F.); (I.M.S.); (M.P.); (L.S.)
| | - Angelo Zullo
- Gastroenterology Unit, ‘Nuovo Regina Margherita’ Hospital, 00153 Rome, Italy;
| | - Matteo Pavoni
- Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy; (G.F.); (I.M.S.); (M.P.); (L.S.)
- Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Laura Saccomanno
- Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy; (G.F.); (I.M.S.); (M.P.); (L.S.)
| | - Tiziana Lazzarotto
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;
| | - Rossana Cavallo
- Microbiology and Virology Unit, University Hospital Città Della Salute e Della Scienza di Torino, 10126 Turin, Italy;
| | - Guido Antonelli
- Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Berardino Vaira
- Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy; (G.F.); (I.M.S.); (M.P.); (L.S.)
- Correspondence: ; Tel./Fax: +390-512-144-140
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18
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Pabla BS, Shah SC, Corral JE, Morgan DR. Increased Incidence and Mortality of Gastric Cancer in Immigrant Populations from High to Low Regions of Incidence: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2020; 18:347-359.e5. [PMID: 31154030 PMCID: PMC6911018 DOI: 10.1016/j.cgh.2019.05.032] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 05/10/2019] [Accepted: 05/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Gastric cancer is the leading cause of infection-related cancer death and the third-leading cause of cancer death worldwide. The effect of immigration on gastric cancer risk is not well-defined but might be helpful for screening or surveillance endeavors. We performed a systematic review and meta-analysis to define the risk of gastric cancer in immigrants from high-incidence regions to low-incidence regions (including Western Europe, Australia, Brazil, Canada, Israel, and the United States). METHODS We searched MEDLINE and EMBASE databases, from January 1980 to January 2019, for studies that identified immigrants from high-incidence regions of gastric cancer, provided clear definitions of immigrant and reference populations, and provided sufficient data to calculate gastric cancer incidence and gastric cancer-related mortality. We performed meta-analyses of standardized incidence ratios (SIR) for first-generation immigrants from high- to low-incidence regions, stratified by immigrant generation, sex, and anatomic and histologic subtype, when data were available. RESULTS We identified 38 cohort studies that met our inclusion criteria. All 13 studies of 21 distinct populations reported significantly increased SIRs for gastric cancer in first-generation foreign-born immigrants (men SIR range, 1.24-4.50 and women SIR range, 1.27-5.05). The pooled SIR for immigrants with all types of gastric cancer was 1.66 (95% CI, 1.52-1.80) for men and 1.83 (95% CI, 1.69-1.98) for women. Nine studies from 2 high-incidence populations (the former Soviet Union and Japan) reported an increased gastric cancer standardized mortality ratio in first-generation immigrants who migrated to regions of low incidence (former Soviet Union immigrants, 1.44-1.91 for men and 1.40-2.56 for women). CONCLUSIONS Immigrants from regions with a high incidence of gastric cancer to regions of low incidence maintain a higher risk of gastric cancer and related mortality, based on a comprehensive systematic review and meta-analysis. Assessment of immigrant generation along with other risk factors might help identify high-risk populations for prevention and therapeutic interventions.
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Affiliation(s)
- Baldeep S Pabla
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine Vanderbilt University Medical Center
| | - Shailja C Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine Vanderbilt University Medical Center
| | | | - Douglas R Morgan
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Nashville, Tennessee; Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, Birmingham, Alabama.
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19
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Yue X, Jiang X, Zou H, Li G, Wang J, Liu Y. Association of hepatocellular carcinoma risk with polymorphisms in tumour necrosis factor alpha gene in a Chinese Han population. Int J Immunogenet 2020; 47:286-293. [PMID: 31943768 DOI: 10.1111/iji.12474] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 12/06/2019] [Accepted: 12/21/2019] [Indexed: 12/20/2022]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Studies have shown that the tumour necrosis factor alpha (TNF-α) plays an important role in the development of HCC; however, the association between genetic variations of TNF-α and HCC is not yet fully understood. To evaluate the correlation of TNF-α polymorphisms with HCC, we randomly selected 327 HCC patients and 432 healthy controls, all these subjects reported Han nationality. Genotyping of four TNF-α SNPs (rs1799724, rs1800629, rs1799964 and rs1800610) was performed using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method. Distributions of rs1799964 genotypes and rs1800610 alleles were found to be significantly different between cases and controls (p = .011, p = .001). The recessive model of rs1799964 significantly increased HCC risk (p = .0015), while the dominant and over-dominant models of rs1800610 significantly reduced HCC risk (p = .0096, p = .014). Haplotype analysis of the four TNF-α SNPs revealed that the TGTA haplotype was associated with a reduced HCC risk (p = .0033, OR = 0.53), while the TGTG haplotype was associated with an increased HCC risk (p = .0032, OR = 9.69). These findings indicated that specific TNF-α polymorphisms may be associated with the susceptibility to HCC.
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Affiliation(s)
- Xin Yue
- Department of Radiology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Xin Jiang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China
| | - Hongjiu Zou
- Changchun International Travel Healthcare Center, Changchun, China
| | - Gaokai Li
- Department of Toxicology, School of Public Health, Jilin University, Changchun, China
| | - Jinan Wang
- Department of Radiology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Ying Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun, China
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20
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Banks M, Graham D, Jansen M, Gotoda T, Coda S, di Pietro M, Uedo N, Bhandari P, Pritchard DM, Kuipers EJ, Rodriguez-Justo M, Novelli MR, Ragunath K, Shepherd N, Dinis-Ribeiro M. British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019; 68:1545-1575. [PMID: 31278206 PMCID: PMC6709778 DOI: 10.1136/gutjnl-2018-318126] [Citation(s) in RCA: 362] [Impact Index Per Article: 60.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 05/06/2019] [Accepted: 05/17/2019] [Indexed: 12/11/2022]
Abstract
Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.
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Affiliation(s)
- Matthew Banks
- University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK.,Research Department of Targeted Intervention, University College London, London, UK
| | - David Graham
- University College London Hospital, University College London Hospitals NHS Foundation Trust, London, UK.,Division of Surgery and Interventional Science, University College London Division of Biosciences, London, UK
| | - Marnix Jansen
- Department of Histopathology, University College London, London, UK
| | - Takuji Gotoda
- Gastroenterology, Nihon University School of Medicine Graduate School of Medicine, Itabashi-ku, Tokyo, Japan
| | | | - Massimiliano di Pietro
- MRC Cancer Unit, University of Cambridge, Cambridge, UK.,Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Endoscopic Training and Learning Center, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | | | - D Mark Pritchard
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | | | | | - Marco R Novelli
- Department of Histopathology, University College London, London, UK
| | - Krish Ragunath
- Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, UK
| | - Neil Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, Gloucestershire, UK
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21
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Abdi E, Latifi-Navid S, Zahri S, Yazdanbod A, Pourfarzi F. Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives. Cancer Med 2019; 8:6114-6126. [PMID: 31448582 PMCID: PMC6792520 DOI: 10.1002/cam4.2497] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 07/17/2019] [Accepted: 08/01/2019] [Indexed: 12/12/2022] Open
Abstract
Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In 2012, 260 000 CGA cases (age‐standardised rate (ASR); 3.3/100 000) and 691 000 NCGA cases (ASR; 8.8/100 000) were reported worldwide. Compared with women, men had greater rates for both the subsites, especially for CGA. Recently, four molecular subtypes of GC have been proposed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG); however, these classifications do not take into account predisposing germline variants and their possible interaction with somatic alterations in carcinogenesis. The etiology of adenocarcinoma of the cardia and the gastroesophageal junction (GEJ) is not known. It is thought that CGA is distinct from adenocarcinomas located in the esophagus or distal stomach, both epidemiologically and biologically. Moreover, CGA is often identified in the advanced stage having a poor prognosis. Therefore, understanding the risk and the role of predisposing factors in etiology of CGA can inform clinical practice and counseling for risk reduction. In this paper, we showed that GC family history, lifestyle, demographics, gastroesophageal reflux disease, Helicobacter pylori infection, and multiple genetic and epigenetic risk factors as well as several predisposing conditions may underlie susceptibility to CGA. However, several genome‐wide association studies (GWASs) should be conducted to identify novel high‐penetrance genes and pathways as well as causal germline variants predisposing to CGA. They must include different ethnic groups, especially from high‐incidence countries for CGA, because some risk loci are ancestry‐specific. In parallel, statistical methods can be developed to identify cancer predisposition genes (CPGs) from tumor sequencing data. It is also necessary to find novel long noncoding RNAs related to the risk of CGA. Taken altogether, new cancer risk prediction models, including all genetic and nongenetic factors influencing risk, should be developed to facilitate risk assessment, disease prevention, and early diagnosis and intervention of CGA in the future.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Abbas Yazdanbod
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farhad Pourfarzi
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
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22
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Sokolova O, Naumann M. Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis. Curr Top Microbiol Immunol 2019; 421:107-137. [PMID: 31123887 DOI: 10.1007/978-3-030-15138-6_5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Over the last years, intensive investigations in molecular biology and cell physiology extended tremendously the knowledge about the association of inflammation and cancer. In frame of this paradigm, the human pathogen Helicobacter pylori triggers gastritis and gastric ulcer disease, and contributes to the development of gastric cancer. Mechanisms, by which the bacteria-induced inflammation in gastric mucosa leads to intestinal metaplasia and carcinoma, are represented in this review. An altered cell-signaling response and increased production of free radicals by epithelial and immune cells account for the accumulation of DNA damage in gastric mucosa, if infection stays untreated. Host genetics and environmental factors, especially diet, can accelerate the process, which offers the opportunity of intervention based on a balanced nutrition. It is supposed that inflammation might influence stem- or progenitor cells in gastric tissue predisposing for metaplasia or tumor relapse. Herein, DNA is strongly mutated and labile, which restricts therapy options. Thus, the understanding of the mechanisms that underlie gastric carcinogenesis will be of preeminent importance for the development of strategies for screening and early detection. As most gastric cancer patients face late-stage disease with a poor overall survival, the development of multi-targeted therapeutic intervention strategies is a major challenge for the future.
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Affiliation(s)
- Olga Sokolova
- Institute of Experimental Internal Medicine, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany
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Norollahi SE, Alipour M, Rashidy-Pour A, Samadani AA, Larijani LV. Regulatory Fluctuation of WNT16 Gene Expression Is Associated with Human Gastric Adenocarcinoma. J Gastrointest Cancer 2019; 50:42-47. [PMID: 29110228 DOI: 10.1007/s12029-017-0022-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Gastric cancer is one of the most serious and lethal kinds of cancer in the world. It is a multi-step, multi-factor, and elaborated process that is associated to gene abnormal expression. This study intended to investigate the WNT16 gene's expression in human gastric tumor and the margin tissues of the stomach (normal tissues). METHODS Correspondingly, 40 samples (20 tumoral tissues and 20 non tumoral or margins tissues) were investigated in Imam Khomeini Hospital in Sari City, Mazandaran Province, Iran. In this way, real-time PCR, Taqman assay was employed to evaluate the upregulation and downregulation of this gene in both tissues in triplicate form. The GAPDH gene was selected as housekeeping gene. RESULTS Conspicuously, the results have shown a remarkable modification in tumoral tissues, and the gene expression increased significantly in tumoral tissue. CONCLUSIONS Conclusively, the upregulation of WNTt16 gene expression in tumoral tissues was impressive and the P value was 0.005 and the SE range was 0.064-142.154.
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Affiliation(s)
- Seyedeh Elham Norollahi
- Faculty of Medicine, Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Majid Alipour
- Department of Biology, Islamic Azad University of Babol, Babol, Iran
| | - Ali Rashidy-Pour
- Faculty of Medicine, Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.,Faculty of Medicine, Department of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Akbar Samadani
- Faculty of Medicine, Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran. .,Faculty of Medicine, Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
| | - Laleh Vahedi Larijani
- Faculty of Medicine, Department of Pathology, Mazandaran University of Medical Sciences, Sari, Iran
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24
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He B, Pan B, Pan Y, Wang X, Zhou L, Sun H, Xu T, Xu X, Liu X, Wang S. Polymorphisms of IL-23R predict survival of gastric cancer patients in a Chinese population. Cytokine 2019; 117:79-83. [DOI: 10.1016/j.cyto.2019.01.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 12/15/2018] [Accepted: 01/27/2019] [Indexed: 12/14/2022]
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25
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Zulfiqar M, Bluth MH, Bhalla A. Molecular Diagnostics in Esophageal and Gastric Neoplasms: 2018 Update. Clin Lab Med 2019; 38:357-365. [PMID: 29776635 DOI: 10.1016/j.cll.2018.02.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease.
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Affiliation(s)
- Muhammad Zulfiqar
- Southeastern Pathology Associates (SEPA Labs), 203 Indigo Drive, Brunswick, GA 31525, USA.
| | - Martin H Bluth
- Southeastern Pathology Associates (SEPA Labs), 203 Indigo Drive, Brunswick, GA 31525, USA; Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA; Pathology Laboratories, Michigan Surgical Hospital, 21230 Dequindre Road, Warren, MI 48091, USA
| | - Amarpreet Bhalla
- Department of Pathology and Anatomical Sciences, Jacobs School of Buffalo, 955 Main Street, Buffalo, NY 14203, USA
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26
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Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences. Curr Top Microbiol Immunol 2019; 421:53-76. [PMID: 31123885 DOI: 10.1007/978-3-030-15138-6_3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host's genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.
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27
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Helicobacter pylori, Peptic Ulcer Disease and Gastric Cancer. GASTROINTESTINAL DISEASES AND THEIR ASSOCIATED INFECTIONS 2019. [DOI: 10.1016/b978-0-323-54843-4.00002-7] [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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28
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Pereira-Marques J, Ferreira RM, Pinto-Ribeiro I, Figueiredo C. Helicobacter pylori Infection, the Gastric Microbiome and Gastric Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1149:195-210. [PMID: 31016631 DOI: 10.1007/5584_2019_366] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
After a long period during which the stomach was considered as an organ where microorganisms could not thrive, Helicobacter pylori was isolated in vitro from gastric biopsies, revolutionising the fields of Microbiology and Gastroenterology. Since then, and with the introduction of high-throughput sequencing technologies that allowed deep characterization of microbial communities, a growing body of knowledge has shown that the stomach contains a diverse microbial community, which is different from that of the oral cavity and of the intestine. Gastric cancer is a heterogeneous disease that is the end result of a cascade of events arising in a small fraction of patients colonized with H. pylori. In addition to H. pylori infection and to multiple host and environmental factors that influence disease development, alterations to the composition and function of the normal gastric microbiome, also known as dysbiosis, may also contribute to malignancy. Chronic inflammation of the mucosa in response to H. pylori may alter the gastric environment, paving the way to the growth of a dysbiotic gastric bacterial community. This dysbiotic microbiome may promote the development of gastric cancer by sustaining inflammation and/or inducing genotoxicity. This chapter summarizes what is known about the gastric microbiome in the context of H. pylori-associated gastric cancer, introducing the emerging dimension of the microbiome into the pathogenesis of this highly incident and deadly disease.
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Affiliation(s)
- Joana Pereira-Marques
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- ICBAS - Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Rui M Ferreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
| | - Ines Pinto-Ribeiro
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
- Faculty of Medicine, University of Porto, Porto, Portugal.
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29
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Moradipour A, Khosravi A, Piri F. Fecal Helicobacter pylori glmM and 16S rRNA genes correlate with serum TNF-α and IL-1β cytokine fluctuations. Acta Microbiol Immunol Hung 2018; 65:489-499. [PMID: 30024269 DOI: 10.1556/030.65.2018.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The proinflammatory cytokines of TNF-α and IL-1β have been reported to be increased in gastric mucosal surfaces in people with Helicobacter pylori infection. Accordingly, this study was conducted to investigate the relationship between the presence of H. pylori genes and the serum oscillations of these cytokines. In this study, DNA was first extracted from the stool samples of infected individuals and used as DNA template to investigate the presence of glmM and 16S rRNA genes in PCR. The ELISA assay was employed to examine serum levels of TNF-α and IL-1β cytokines. According to statistical analysis, there was a significant correlation between the presence of glmM and 16S rRNA genes in the stool samples of infected persons and the serum oscillations of TNF-α and IL-1β cytokines. At the end of study and analysis of the data in case group with HPSAg+, 47.6% of the glmM gene and 23.6% of the 16S rRNA gene were positive. In addition, a significant correlation was observed between the presence of glmM and 16S rRNA genes in the stool specimens of infected individuals and the serum levels of TNF-α and IL-1β cytokines (p < 0.05). Considering the results, it can be concluded that fluctuations in the amount of HPSA, TNF-α, and IL-1β in H. pylori infection depend on the presence of glmM and 16S rRNA genes. The presence of glmM and 16S rRNA in the stool sample increases by boosting the response level to stool antigen (HPSA), IL-1β, and TNF-α, suggesting the prognosis of the disease with a bacterial virulence form using stool tests.
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Affiliation(s)
- Ayat Moradipour
- 1 Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Afra Khosravi
- 2 Faculty of Medicine, Department of Immunology, Medical University of Ilam, Ilam, Iran
| | - Fatemeh Piri
- 3 Faculty of Medicine, Department of Anatomy, Lorestan University of Medical Sciences, Khorramabad, Iran
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30
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Tavera G, Morgan DR, Williams SM. Tipping the Scale Toward Gastric Disease: A Host-Pathogen Genomic Mismatch? CURRENT GENETIC MEDICINE REPORTS 2018; 6:199-207. [PMID: 30775159 PMCID: PMC6373874 DOI: 10.1007/s40142-018-0153-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Chronic infection with Helicobacter pylori infection is necessary but not sufficient to initiate development of intestinal-type gastric adenocarcinoma. It is not clear what additional factors tip the scale from commensal bacteria towards a pathogen that facilitates development of gastric cancer. Genetic variants in both the pathogen and host have been implicated, but neither alone explains a substantial portion of disease risk. RECENT FINDINGS In this review, we consider studies that address the important role of human and bacterial genetics, ancestry and their interactions in determining gastric disease risk. We observe gaps in the current literature that should guide future work to confirm the hypothesis of the interacting roles of host and bacterial genetics that will be necessary to translate these findings into clinically relevant information. SUMMARY We summarize genetic risk factors for gastric disease in both H. pylori and human hosts. However, genetic variation of one or the other organism in isolation insufficiently explains gastric disease risk. The most promising models of gastric disease risk simultaneously consider the genetic variation of both the H. pylori and human host, under a co-evolution model.
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Affiliation(s)
- Gloria Tavera
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
| | - Douglas R Morgan
- Vanderbilt Ingram Cancer Center, Nashville, Tennessee
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Scott M Williams
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
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31
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He B, Xu T, Pan B, Pan Y, Wang X, Dong J, Sun H, Xu X, Liu X, Wang S. Polymorphisms of TGFBR1, TLR4 are associated with prognosis of gastric cancer in a Chinese population. Cancer Cell Int 2018; 18:191. [PMID: 30479570 PMCID: PMC6245525 DOI: 10.1186/s12935-018-0682-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 11/09/2018] [Indexed: 12/14/2022] Open
Abstract
Background Helicobacter pylori (H. pylori)-induced gastric cancer is an intricate progression of immune response against H. pylori infection. IL-16, TGF-β1 and TLR4 pathways were the mediators involved in the immune response. We hypothesized that genetic variations in genes of these pathways have potential susceptibility to gastric cancer risk, and predict clinical outcomes of patients. Methods To investigate the susceptibility and prognostic value of genetic variations of IL-16, TGFBR1 and TLR4 pathways to gastric cancer, we performed a case–control study combined a retrospective study in a Chinese population. Genotyping for all polymorphisms was based on the Sequenom’s MassARRAY platform, and H. pylori infection was determined by using an immunogold testing kit. Results We found rs10512263 CC genotype was found to be a decreased risk of gastric cancer (CC vs. TT: adjusted OR = 0.54, 95% CI 0.31–0.97); however, rs334348 GG genotype was associated with increased risk of gastric cancer (GG vs. AA: adjusted OR = 1.51, 95% CI 1.05–2.18). We found that carriers harboring rs1927911 A allele (GA/AA) or rs10512263 C allele (CT/CC) have unfavorable survival time than none carriers (rs1927911: GA/AA vs. GG: adjusted HR = 1.27, 95% CI 1.00–1.63; rs10512263: CT/CC vs. TT: adjusted HR = 1.29, 95% CI 1.02–1.63) and that individuals harboring both two minor alleles (rs1927911 GA/AA and rs10512263 CT/CC) suffered a significant unfavorable survival (adjusted HR = 1.64, 95% CI 1.17–2.31). Conclusion In short, we concluded that two polymorphisms (rs334348, rs10512263) in TGFBR1 were associated with risk of gastric cancer, and that TLR4 rs1927911 and TGFBR1 rs10512263 were associated with clinical outcomes of gastric cancer patients. Electronic supplementary material The online version of this article (10.1186/s12935-018-0682-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Bangshun He
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China.,2Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 210000 China
| | - Tao Xu
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China
| | - Bei Pan
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China
| | - Yuqin Pan
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China.,2Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 210000 China
| | - Xuhong Wang
- 3Medical College, Southeast University, Nanjing, 210000 China
| | - Jingwu Dong
- Digestive Department, Xuyi People's Hospital, Huaian, 211700 China
| | - Huiling Sun
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China.,2Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 210000 China
| | - Xueni Xu
- 3Medical College, Southeast University, Nanjing, 210000 China
| | - Xiangxiang Liu
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China
| | - Shukui Wang
- 1General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006 China.,2Helicobacter pylori Research Key Laboratory, Nanjing Medical University, Nanjing, 210000 China
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Sultana Z, Bankura B, Pattanayak AK, Sengupta D, Sengupta M, Saha ML, Panda CK, Das M. Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2018; 59:653-667. [PMID: 30094865 DOI: 10.1002/em.22208] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 03/18/2018] [Accepted: 05/03/2018] [Indexed: 06/08/2023]
Abstract
Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1β and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL-1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 "effective" risk alleles conferred a risk of almost 10-fold in comparison to individuals carrying less than 3 "effective" risk alleles. Our survival analysis also indicated a significant association between IL-1β rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL-1β rs1143627:CC and rs16944:TT genotypes. Further, meta-analysis revealed significant association of IL-1β rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653-667, 2018. © 2018 Wiley Periodicals, Inc.
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Affiliation(s)
- Zareen Sultana
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | - Biswabandhu Bankura
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | | | - Debmalya Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Mainak Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Makhan Lal Saha
- Department of Surgery, Institute of Post Graduate Medical Education &Research, Kolkata, West Bengal, 700020, India
| | - Chinmay Kumar Panda
- Department of Oncogene Regulation and Viral Associated Human Cancer, Chittaranjan Cancer Research Institute, Kolkata, West Bengal, 700026, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
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Waddingham W, Graham D, Banks M, Jansen M. The evolving role of endoscopy in the diagnosis of premalignant gastric lesions. F1000Res 2018; 7. [PMID: 29946429 PMCID: PMC5998031 DOI: 10.12688/f1000research.12087.1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/01/2018] [Indexed: 12/18/2022] Open
Abstract
Gastric adenocarcinoma is a disease that is often detected late, at a stage when curative treatment is unachievable. This must be addressed through changes in our approach to the identification of patients at increased risk by improving the detection and risk assessment of premalignant changes in the stomach, including chronic atrophic gastritis and intestinal metaplasia. Current guidelines recommend utilising random biopsies in a pathology-led approach in order to stage the extent and severity of gastritis and intestinal metaplasia. This random method is poorly reproducible and prone to sampling error and fails to acknowledge recent advances in our understanding of the progression to gastric cancer as a non-linear, branching evolutionary model. Data suggest that recent advances in endoscopic imaging modalities, such as narrow band imaging, can achieve a high degree of accuracy in the stomach for the diagnosis of these premalignant changes. In this review, we outline recent data to support a paradigm shift towards an endoscopy-led approach to diagnosis and staging of premalignant changes in the stomach. High-quality endoscopic interrogation of the chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to more accurate risk assessment, with reduced rates of under or missed diagnoses.
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Affiliation(s)
- William Waddingham
- Department of Endoscopy, University College London Hospital, London, UK.,UCL Cancer Institute, University College London, London, UK
| | - David Graham
- Department of Endoscopy, University College London Hospital, London, UK
| | - Matthew Banks
- Department of Endoscopy, University College London Hospital, London, UK
| | - Marnix Jansen
- UCL Cancer Institute, University College London, London, UK.,Department of Pathology, University College London, London, UK
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Miernyk KM, Bulkow LR, Gold BD, Bruce MG, Hurlburt DH, Griffin PM, Swerdlow D, Cook K, Hennessy T, Parkinson AJ. Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies. Helicobacter 2018; 23. [PMID: 29537130 PMCID: PMC6640139 DOI: 10.1111/hel.12482] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old. RESULTS We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered. CONCLUSIONS Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.
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Affiliation(s)
- KM Miernyk
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
| | - LR Bulkow
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
| | - BD Gold
- Children’s Center for Digestive Healthcare, LLC; Atlanta, Georgia USA
| | - MG Bruce
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
| | - DH Hurlburt
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
| | - PM Griffin
- Enteric Diseases Epidemiology Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Atlanta, Georgia USA
| | - D Swerdlow
- Enteric Diseases Epidemiology Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Atlanta, Georgia USA
| | - K Cook
- Kiel Laboratories, Inc.; Flowery Branch, Georgia USA
| | - T Hennessy
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
| | - AJ Parkinson
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention; Anchorage, Alaska USA
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35
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Agudo A, Cayssials V, Bonet C, Tjønneland A, Overvad K, Boutron-Ruault MC, Affret A, Fagherazzi G, Katzke V, Schübel R, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Grioni S, Tumino R, Ricceri F, Panico S, Bueno-de-Mesquita B, Peeters PH, Weiderpass E, Skeie G, Nøst TH, Lasheras C, Rodríguez-Barranco M, Amiano P, Chirlaque MD, Ardanaz E, Ohlsson B, Dias JA, Nilsson LM, Myte R, Khaw KT, Perez-Cornago A, Gunter M, Huybrechts I, Cross AJ, Tsilidis K, Riboli E, Jakszyn P. Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am J Clin Nutr 2018; 107:607-616. [PMID: 29635497 DOI: 10.1093/ajcn/nqy002] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 12/26/2017] [Indexed: 12/13/2022] Open
Abstract
Background Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. Objective We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. Design A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. Results The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Conclusions Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.
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Affiliation(s)
- Antonio Agudo
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Valerie Cayssials
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Catalina Bonet
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Kim Overvad
- Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
| | | | - Aurélie Affret
- CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif, France
- Gustave Roussy, Villejuif, France
| | - Guy Fagherazzi
- CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif, France
- Gustave Roussy, Villejuif, France
| | - Verena Katzke
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
| | - Ruth Schübel
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece
- 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
| | - Carlo La Vecchia
- Hellenic Health Foundation, Athens, Greece
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, "Civic-M.P.Arezzo" Hospital, Ragusa, Italy
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Italy
| | - Salvatore Panico
- Dipartamento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Bas Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, United Kingdom
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Petra H Peeters
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Theresa H Nøst
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Cristina Lasheras
- Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Asturias, Spain
| | - Miguel Rodríguez-Barranco
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
| | - Pilar Amiano
- CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
- Public Health Department of Gipuzkoa, Government of the Basque Country, San Sebastian, Spain
- BioDonostia Research Institute, San Sebastian, Spain
| | - María-Dolores Chirlaque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - Eva Ardanaz
- CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
- Navarra Public Health Institute, IdiSNA (Navarra Institute for Health Research), Pamplona, Spain
| | - Bodil Ohlsson
- Lund University, Skane University Hospital, Division of Internal Medicine, Malmö, Sweden
| | - Joana A Dias
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University. Malmö, Sweden
| | - Lena M Nilsson
- Public Health and Clinical Medicine, Nutritional Research and
| | - Robin Myte
- Public Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Kay-Tee Khaw
- University of Cambridge, Cambridge, United Kingdom
| | - Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Marc Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Inge Huybrechts
- Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
| | - Amanda J Cross
- School of Public Health, Imperial College London, United Kingdom
| | - Kostas Tsilidis
- School of Public Health, Imperial College London, United Kingdom
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elio Riboli
- School of Public Health, Imperial College London, United Kingdom
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
- Facultat Ciències Salut Blanquerna, Universitat Ramon Llull, Barcelona, Spain
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36
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Xia Y, Zhang X, Bo A, Sun J, Li M. Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells. Oncol Lett 2018; 15:6622-6628. [PMID: 29616124 DOI: 10.3892/ol.2018.8111] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 12/14/2017] [Indexed: 01/28/2023] Open
Abstract
The objective of the present study was to investigate the cytotoxic effects of sodium citrate on human gastric adenocarcinoma epithelia AGS cells. Numerous cytotoxicity-associated sodium citrate-induced effects were assessed, including cell viability and proliferation, cytokine expression and caspase activity. In vitro studies demonstrated that incubation with sodium citrate (>3.125 mM) inhibited AGS cell viability and proliferation in a dose-dependent manner. Incubation with sodium citrate for 24 h revealed that the levels of interleukin-1β (IL-1β), IL-8 and tumor necrosis factor increased with an increasing of dose of sodium citrate, whereas the IL-6 levels exhibited only a slight alteration. In addition, increases in caspase-3 and -9 activities were associated with increased duration of treatment and dosage of sodium citrate. Collectively, the results of the present study demonstrated that treatment with sodium citrate at higher concentrations or for longer durations exerts a cytotoxic effect on AGS cells via the induction of the intrinsic apoptosis pathway and the alteration in the levels of certain cytokines.
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Affiliation(s)
- Yuan Xia
- Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Inner Mongolia Autonomous Region 010021, P.R. China.,School of Public Health, Inner Mongolia Medical University, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Xulong Zhang
- Department of Immunology, College of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China
| | - Agula Bo
- School of Public Health, Inner Mongolia Medical University, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Juan Sun
- School of Public Health, Inner Mongolia Medical University, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Minhui Li
- Department of National Medicine, Inner Mongolia Institute of Chinese Medicine, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China
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37
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Burkitt MD, Duckworth CA, Williams JM, Pritchard DM. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models. Dis Model Mech 2017; 10:89-104. [PMID: 28151409 PMCID: PMC5312008 DOI: 10.1242/dmm.027649] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.
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Affiliation(s)
- Michael D Burkitt
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK
| | - Carrie A Duckworth
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK
| | - Jonathan M Williams
- Pathology and Pathogen Biology, Royal Veterinary College, North Mymms AL9 7TA, UK
| | - D Mark Pritchard
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK
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38
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Petra CV, Rus A, Dumitraşcu DL. Gastric microbiota: tracing the culprit. ACTA ACUST UNITED AC 2017; 90:369-376. [PMID: 29151783 PMCID: PMC5683824 DOI: 10.15386/cjmed-854] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Accepted: 08/02/2017] [Indexed: 12/15/2022]
Abstract
The gastric environment has been long time considered bacteria-free, but the discovery of Helicobacter pylori (H. pylori) in 1982 superseded this conception. Over the last decades new diagnostic methods have been developed, starting with culture-dependent and advancing to culture-independent ones. These modern techniques provide new insight into the composition and influence of this ecosystem on the entire gastrointestinal tract. H. pylori is no longer considered the only microorganism in the stomach, other non-H. pylori microbial species may populate the same environment and exercise their role. Current knowledge suggests possible links of these bacteria with gastroduodenal diseases, such as peptic ulcer and gastric cancer but most of them need further scientific evidence. This review summarizes current information on these complex interrelations between gastric microbial communities and host in health and disease.
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Affiliation(s)
- Cristian Vasile Petra
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Aronel Rus
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dan Lucian Dumitraşcu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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39
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Impact of aging on distribution of IgA + and IgG + cells in aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus). Exp Gerontol 2017; 100:36-44. [PMID: 28989079 DOI: 10.1016/j.exger.2017.09.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 09/06/2017] [Accepted: 09/27/2017] [Indexed: 02/07/2023]
Abstract
The aggregated lymphoid nodules area (ALNA) in the abomasum is a special organized lymphoid tissue discovered only in Bactrian camels at present. This study aimed to explore the impact of aging on distribution of IgA+ and IgG+ cells in ALNA in abomasum of Bactrian camels. Twenty-four Alashan Bactrian camels were divided into the following four age groups: young (1-2years), pubertal (3-5years), middle-aged (6-16years) and old (17-20years). IgA+ and IgG+ cells in the lamina propria of ALNA were observed and analyzed using immunohistochemical and statistical techniques. The results showed that, in ALNA, the distribution of IgA+ and IgG+ cells were diffuse, and only a few were in subepithelium dome (SED) and most of them in non-SED. Meanwhile, there were significantly more IgA+ cells than IgG+ cells in SED from the young to the middle aged group, but which reversed in old group (P<0.05). However, the aging significantly decreased the densities of IgA+ and IgG+ cells populations in non-SED (P<0.05); in SED, there were no significant differences between the densities of IgA+ and IgG+ cells, but which were both significantly lower in old group than those in young group (P<0.05). The results demonstrated that, in mucosal effector sites, the aging significantly decreased the densities of IgA+ and IgG+ cells populations and impacted on the defense barriers formed by IgA and IgG, but had no impact on the scattered characteristics. In inductive sites, the aging dramatically declined their densities, and they should have close relationships with immune memory. These findings lay the foundation for further researching the mucosal immune disorder or decline caused by aging, and especially underscore the importance of researching the impact of aging on the relationship between IgA+ and IgG+ cells populations and the microbiota colonized in abomasum of Bactrian camels.
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40
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Chang WL, Lin MY, Kuo HY, Yang HB, Cheng HC, Lu CC, Sheu BS. Osteopontin polymorphism increases gastric precancerous intestinal metaplasia susceptibility in Helicobacter pylori infected male. Future Oncol 2017; 13:1415-1425. [PMID: 28685609 DOI: 10.2217/fon-2017-0006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
AIM Whether genetic polymorphisms of osteopontin (OPN) coding gene, SPP1, determine the risk of gastric precancerous intestinal metaplasia (IM) in Helicobacter pylori infected patients. PATIENTS & METHODS Helicobacter pylori infected patients (100 with and 210 without IM) were recruited to evaluate the associations of SPP1 promoter polymorphisms with gastric IM and adjusted for age, sex and smoking. Gastric OPN expression and inflammation were evaluated by immunohistochemistry, and haemotoxylin and eosin stain. RESULTS Only in males, but not females, carriage of both GG genotype at rs11730059 and C-G-C haplotype at rs6833161-rs2853744-rs11730582 significantly increased the IM risk (OR: 4.92; 95% CI: 1.65-14.65; p = 0.004). Nearly 87.5% of males with IM carried risky genotype or haplotype. Carriers of the risky genotype or haplotype also had increased gastric OPN expression (p = 0.038) and inflammation (p = 0.007). CONCLUSION SPP1 polymorphisms predispose to IM development in H. pylori infected males.
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Affiliation(s)
- Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Ying Lin
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsin-Yu Kuo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsiao-Bai Yang
- Department of Pathology, Ton-Yen General Hospital, Hsin-Chu, Taiwan
| | - Hsiu-Chi Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Cheng-Chan Lu
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Internal Medicine, Tainan Hospital, Ministry of Health & Welfare, Tainan, Taiwan
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41
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Zheng W, Zhang S, Zhang S, Min L, Wang Y, Xie J, Hou Y, Tian X, Cheng J, Liu K, Xu D, Yu X, Liu Z, Lv Y, Liang N, Zhang J, Liu F, Tian Y. The relationship between tumor necrosis factor-α polymorphisms and gastric cancer risk: An updated meta-analysis. Biomed Rep 2017; 7:133-142. [PMID: 28804625 PMCID: PMC5526040 DOI: 10.3892/br.2017.934] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 06/21/2017] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to evaluate the relationship between tumor necrosis factor-α (TNF-α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10–1.23)]. In analysis stratified by ethnicity, TNF-α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02–1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79–1.18)]. The overall ORs (95% CIs) for TNF-α 857, TNF-α 1031 and TNF-α 863 were 1.13 (1.04–1.24), 0.94 (0.85–1.05) and 0.89 (0.78–1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03–1.31)]. TNF-α 308 and TNF-α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-α 1031 and TNF-α 863 were not significantly associated with gastric cancer risk.
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Affiliation(s)
- Wenxian Zheng
- Department of Oncology, Shanghai Jiaotong University Affiliated Sixth People Hospital, Shanghai 200233, P.R. China
| | - Shuisheng Zhang
- Department of Abdominal Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Shenfeng Zhang
- Department of Oncology, Zaozhuang Municipal Hospital of Shandong Province, Zaozhuang, Shandong 277101, P.R. China
| | - Li Min
- Department of Gastroenterology, Beijing Medical University, National Clinical Center for Digestive Disease Center, Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China
| | - Yihong Wang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jian Xie
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yong Hou
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Xiufang Tian
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jian Cheng
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Kun Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Deguo Xu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Xinshuang Yu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Zhen Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yajuan Lv
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Ning Liang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jiandong Zhang
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Fengjun Liu
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Yuan Tian
- Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
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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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43
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Petkevicius V, Salteniene V, Juzenas S, Wex T, Link A, Leja M, Steponaitiene R, Skieceviciene J, Kupcinskas L, Jonaitis L, Kiudelis G, Malfertheiner P, Kupcinskas J. Polymorphisms of microRNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer. World J Gastroenterol 2017; 23:3480-3487. [PMID: 28596683 PMCID: PMC5442083 DOI: 10.3748/wjg.v23.i19.3480] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 02/23/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population.
METHODS Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and IL10 T>C (rs3024498) SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex, age and country of birth.
RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690. The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls (23.26% and 19.19% respectively, P = 0.028). CT genotype was also more prevalent in patients compared to control group (38.48% and 30.12% respectively, P < 0.021). Logistic regression analysis revealed that only one polymorphism (rs1051690 in INSR gene) was associated with increased risk of GC. Carriers of CT genotype had higher odds of GC when compared to CC genotype (OR = 1.45, 95%PI: 1.08-1.95, P = 0.01). Similar association was observed in a dominant model for INSR gene, where comparison of TT+CT vs CC genotypes showed an increased risk of GC (OR = 1.44, 95%PI: 1.08-1.90, P = 0.01). Other analyzed SNPs were not associated with the presence of GC.
CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of GC.
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44
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Abstract
The esophagus and stomach are host to their own population of bacteria, which differs in health and disease. Helicobacter pylori uniquely colonizes only gastric mucosa, but an increasing number of bacteria is now isolated from the gastric juice and gastric mucosa, including Lactobacillus. The presence of H pylori alters populations of other gastric bacteria with a marked reduction in diversity. Alterations in intragastric acidity may be the cause or the consequence of changes in the microbial populations of the stomach. Esophageal inflammation is associated with an altered microbiota in gastroesophageal reflux disease, Barrett's esophagus, eosinophilic esophagitis, and cancer.
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45
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Boland CR, Yurgelun MB. Historical Perspective on Familial Gastric Cancer. Cell Mol Gastroenterol Hepatol 2017; 3:192-200. [PMID: 28275686 PMCID: PMC5331778 DOI: 10.1016/j.jcmgh.2016.12.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 12/25/2016] [Indexed: 12/18/2022]
Abstract
Gastric cancer is a common disease worldwide, typically associated with acquired chronic inflammation in the stomach, related in most instances to infection by Helicobacter pylori. A small percentage of cases occurs in familial clusters, and some of these can be linked to specific germline mutations. This article reviews the historical background to the current understanding of familial gastric cancer, focuses on the entity of hereditary diffuse gastric cancer, and also reviews the risks for gastric cancer related to a number of other familial genetic diseases.
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Affiliation(s)
- C. Richard Boland
- Division of GI, University of California San Diego School of Medicine, San Diego, California,Correspondence Address correspondence to: C. Richard Boland, MD, UCSD School of Medicine, San Diego, California 92110.UCSD School of MedicineSan DiegoCalifornia 92110
| | - Matthew B. Yurgelun
- Dana-Farber Cancer Institute, Boston, Massachusetts,Matthew B. Yurgelun, MD, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana 1126, Boston, Massachusetts 02215. fax: (617) 632–5370.Dana-Farber Cancer Institute450 Brookline AvenueDana 1126BostonMassachusetts 02215
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46
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Rivas-Ortiz CI, Lopez-Vidal Y, Arredondo-Hernandez LJR, Castillo-Rojas G. Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection. Front Med (Lausanne) 2017; 4:47. [PMID: 28512631 PMCID: PMC5411440 DOI: 10.3389/fmed.2017.00047] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 04/07/2017] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, β-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3β, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2) have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.
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Affiliation(s)
- Claudia I. Rivas-Ortiz
- Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Yolanda Lopez-Vidal
- Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | | | - Gonzalo Castillo-Rojas
- Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- *Correspondence: Gonzalo Castillo-Rojas,
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47
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Zhang S, Wang XB, Han YD, Wang C, Zhou Y, Zheng F. Certain Polymorphisms in SP110 Gene Confer Susceptibility to Tuberculosis: A Comprehensive Review and Updated Meta-Analysis. Yonsei Med J 2017; 58:165-173. [PMID: 27873510 PMCID: PMC5122633 DOI: 10.3349/ymj.2017.58.1.165] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 01/14/2016] [Accepted: 06/02/2016] [Indexed: 12/22/2022] Open
Abstract
PURPOSE Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14-1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84-4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05-1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14-1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18-4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.
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Affiliation(s)
- Shuai Zhang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xue Bin Wang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Ya Di Han
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chen Wang
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Ye Zhou
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Fang Zheng
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, Hubei, China.
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48
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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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49
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Tumor Necrosis Factor- α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis. DISEASE MARKERS 2016; 2016:4580323. [PMID: 28115787 PMCID: PMC5223007 DOI: 10.1155/2016/4580323] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 12/04/2016] [Accepted: 12/06/2016] [Indexed: 01/08/2023]
Abstract
Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study.
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50
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Hugen S, Thomas RE, German AJ, Burgener IA, Mandigers PJJ. Gastric carcinoma in canines and humans, a review. Vet Comp Oncol 2016; 15:692-705. [PMID: 27549077 DOI: 10.1111/vco.12249] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 05/06/2016] [Accepted: 05/20/2016] [Indexed: 02/06/2023]
Abstract
Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.
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Affiliation(s)
- S Hugen
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - R E Thomas
- Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - A J German
- School of Veterinary Science, University of Liverpool, Neston, UK
| | - I A Burgener
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - P J J Mandigers
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
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