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Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide. BIOMED RESEARCH INTERNATIONAL 2019; 2019:4636804. [PMID: 30863778 PMCID: PMC6378787 DOI: 10.1155/2019/4636804] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 11/01/2018] [Accepted: 11/08/2018] [Indexed: 01/19/2023]
Abstract
Sulfiredoxin (Srx) is a newly discovered antioxidant enzyme playing a role in the catalytic reduction of oxidative modifications. Srx is overexpressed in a variety of cancers. It may promote carcinogenesis as well as tumor progression. In this study, we report for the first time that Srx expression might be positively associated with the development of gastric cancer and tumor malignancy. Immunohistochemistry showed that, compared to normal tissues (42%, 20/47), Srx expression in gastric tumors (85%, 40/47) was much more common (chi-square test, p<0.01). In addition, the staining of Srx was stronger in poorly differentiated gastric cancer than in well-differentiated gastric cancer. Western blotting showed that, in the gastric tumor cell line BGC823, the Srx protein was upregulated in response to H2O2 treatment, although it was inadequate to counteract the increased oxidative stress, as indicated by the gradually increasing level of malondialdehyde (MDA). In addition, Srx expression, MDA levels, and ROS levels in BGC823 cells were markedly inhibited upon treatment with diallyl trisulfide (DATS), a major constituent of garlic oil with proven anticancer effects. These results suggest that Srx may be an oxidative stress marker. Antioxidation may account for the anticancer potential of garlic.
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Nie Y, Wu K, Yu J, Liang Q, Cai X, Shang Y, Zhou J, Pan K, Sun L, Fang J, Yuan Y, You W, Fan D. A global burden of gastric cancer: the major impact of China. Expert Rev Gastroenterol Hepatol 2017; 11:651-661. [PMID: 28351219 DOI: 10.1080/17474124.2017.1312342] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Gastric cancer (GC) is a highly aggressive cancer and a major cause of cancer-related deaths worldwide. Approximately half of the world's GC cases and deaths occur in china. GC presents challenges in early diagnosis and effective therapy due to a lack of understanding of the underlying molecular biology. The primary goals of this review are to outline current GC research in china and describe future trends in this field. Areas covered: This review mainly focuses on a series of GC-related advances China has achieved. Considerable progress has been made in understanding the role of H. pylori in GC by a series of population-based studies in well-established high-risk areas; A few germline and somatic alterations have been identified by 'omics' studies; Studies on the mechanisms of malignant phenotypes have helped us to form an in-depth understanding of GC and advance drug discovery. Moreover, identification of potential biomarkers and targeted therapies have facilitated the diagnosis and treatment of GC. However, many challenges remain. Expert commentary: To combat GC, sufficient funding is important. More attention should be paid on early diagnosis and the discovery of novel efficient biomarkers and the development of biomarker-based or targeted therapeutics in GC.
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Affiliation(s)
- Yongzhan Nie
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Kaichun Wu
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jun Yu
- b Department of Medicine and Therapeutics and Institute of Digestive Disease , Chinese University of Hong Kong , Hong Kong , China
| | - Qiaoyi Liang
- b Department of Medicine and Therapeutics and Institute of Digestive Disease , Chinese University of Hong Kong , Hong Kong , China
| | - Xiqiang Cai
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Yulong Shang
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jinfeng Zhou
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Kaifeng Pan
- c Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology , Peking University Cancer Hospital & Institute , Beijing , China
| | - Liping Sun
- d Tumor Etiology and Screening, Department of Cancer Institute and General Surgery , The First Affiliated Hospital of China Medical University , Shenyang , China
| | - Jingyuan Fang
- e Renji Hospital , Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Yuan Yuan
- d Tumor Etiology and Screening, Department of Cancer Institute and General Surgery , The First Affiliated Hospital of China Medical University , Shenyang , China
| | - Weicheng You
- c Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology , Peking University Cancer Hospital & Institute , Beijing , China
| | - Daiming Fan
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
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Abstract
This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.
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Affiliation(s)
- Mārcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia.,Riga East University Hospital, Riga, Latvia.,Digestive Diseases Centre GASTRO, Riga, Latvia
| | | | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Pan KF, Zhang L, Gerhard M, Ma JL, Liu WD, Ulm K, Wang JX, Zhang L, Zhang Y, Bajbouj M, Zhang LF, Li M, Vieth M, Liu RY, Quante M, Wang LH, Suchanek S, Zhou T, Guan WX, Schmid R, Classen M, You WC. A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication. Gut 2016; 65:9-18. [PMID: 25986943 DOI: 10.1136/gutjnl-2015-309197] [Citation(s) in RCA: 136] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 04/24/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. DESIGN A total of 184,786 residents aged 25-54 years were enrolled in this trial and received (13)C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. RESULTS The prevalence of H. pylori in trial participants was 57.6%. A total of 94,101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baseline-value of (13)C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all Ptrend<0.001). However, a dose-response relationship between failure rate and smoking or drinking index was found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. CONCLUSIONS This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. TRIAL REGISTRATION NUMBER ChiCTR-TRC-10000979 in accordance with WHO ICTRP requirements.
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Affiliation(s)
- Kai-feng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Jun-ling Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Kurt Ulm
- Technische Universität München, Munich, Germany
| | | | - Lei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | | | - Ming Li
- Healthy Bureau of Linqu County, Weifang, China
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | | | | | - Le-hua Wang
- Healthy Bureau of Linqu County, Weifang, China
| | - Stepan Suchanek
- Department of Medicine, 1st Faculty of Medicine, Military University Hospital, Charles University, Prague, Czech Republic
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei-xiang Guan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Meinhard Classen
- Technische Universität München, Munich, Germany International Digestive Cancer Alliance, Germany
| | - Wei-cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
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Ghasemi-Kebria F, Ghaemi E, Azadfar S, Roshandel G. Epidemiology of Helicobacter pylori infection among Iranian children. Arab J Gastroenterol 2013; 14:169-172. [DOI: 10.1016/j.ajg.2013.11.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 08/14/2013] [Accepted: 11/19/2013] [Indexed: 12/18/2022]
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Pan KF, Formichella L, Zhang L, Zhang Y, Ma JL, Li ZX, Liu C, Wang YM, Goettner G, Ulm K, Classen M, You WC, Gerhard M. Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population. Int J Cancer 2013; 134:2118-25. [PMID: 24155048 DOI: 10.1002/ijc.28560] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 10/04/2013] [Indexed: 12/18/2022]
Abstract
Helicobacter pylori-specific proteins are involved in gastric carcinogenesis. To investigate the seroprevalence of six H. pylori-specific antibodies in patients with different gastric histology, and the impact of seropositivities on the evolution of precancerous gastric lesions, a follow-up study was conducted in Linqu County, China. The seropositivities for CagA, VacA, GroEL, UreA, HcpC and gGT were assessed by recomLine analysis in 573 H. pylori-positive subjects and correlated with evolution of precancerous gastric lesions. We found that the score of H. pylori recomLine test was significantly increased in subjects with chronic atrophic gastritis (CAG, p < 0.0001) or intestinal metaplasia (IM, p = 0.0125), and CagA was an independent predictor of advanced gastric lesions, adjusted odds ratios (ORs) were 2.54 (95% CI = 1.42-4.55) for IM and 2.38 (95% CI = 1.05-5.37) for dysplasia (DYS). Moreover, seropositivities for CagA and GroEL were identified as independent predictors for progression of gastric lesions in a longitudinal study, and ORs were 2.89 (95% CI = 1.27-6.59) and 2.20 (95% CI = 1.33-3.64), respectively. Furthermore, the risk of progression was more pronounced in subjects with more than three positive antigens (p(for) trend = 0.0003). This population-based study revealed that seropositivities for CagA and GroEL might be potential markers to identify patients infected with high-risk H. pylori strains, which are related to the development of GC in a Chinese high-risk population, and recomLine test might serve as a tool for risk stratification.
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Affiliation(s)
- Kai-Feng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
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A placebo-controlled trial of 10-day bismuth-based quadruple therapy to eradicate Helicobacter pylori infection; a pilot study for the large Linqu County trial. Eur J Gastroenterol Hepatol 2010; 22:597-601. [PMID: 19996977 DOI: 10.1097/meg.0b013e3283337146] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM To explore a low-cost and highly-effective therapy for eradication of Helicobacter pylori (H. pylori), a placebo-controlled trial of quadruple therapy was conducted in a population at high risk of gastric cancer in Linqu County of Shandong Province, China. METHODS Two hundred and seventy-seven adults aged 35-54 years with H. pylori infection in three villages were assigned to two groups: treatment (n=189 in two villages) and placebo (n=88 in one village). Participants received either a 10-day oral quadruple therapy regimen with omeprazole (20 mg, twice daily); tetracycline (750 mg, three times daily); metronidazole (500 mg, three times daily) and bismuth potassium citrate (300 mg, twice daily), or a similar lookalike placebo regimen. The status of H. pylori infection in each trial participant before and after six weeks of treatment was determined by a 13C-urea breath test. RESULTS One hundred and seventy-four of 189 participants completed the quadruple therapy (92.1%) and 84 participants completed the placebo therapy (95.5%). The H. pylori eradication rate by intention-to-treat analysis was 76.7% (145 of 189) in the treatment group and 1.1% (1 of 88) in the placebo group, respectively; by per-protocol analysis it was 83.3% (145 of 174) in the treatment group and 1.2% (1 of 84) in the placebo group, respectively. CONCLUSION In a high-risk area of gastric cancer, we conducted a high compliance, tolerable, low side-effect and lowcost therapy of anti-H. pylori. The eradication rate of the 10-day quadruple treatment was more than 80% and significantly higher than the triple therapy regimen used in this population in an earlier trial.
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Li ZW, Wu Y, Sun Y, Liu LY, Tian MM, Feng GS, You WC, Li JY. Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia. World J Gastroenterol 2010; 16:1788-94. [PMID: 20380014 PMCID: PMC2852830 DOI: 10.3748/wjg.v16.i14.1788] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM).
METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing.
RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection.
CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.
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Abstract
In Asia, the prevalence of Helicobacter pylori (H. pylori) infection varies markedly in different countries. Higher prevalence rates are found in developing Asian countries while lower rates have been reported in more industrialized and developed countries. Within a country, the seroprevalence rates may vary between distinct geographic regions. H. pylori infection is an important etiological factor for the occurrence of non-cardia gastric adenocarcinoma. The incidence rate of gastric adenocarcinoma in Asia tends to mirror the seroprevalence rate of H. pylori infection; however, there are populations with high seroprevalence rates of H. pylori infection that paradoxically have low incidence rates of gastric adenocarcinoma. These diverse clinical outcomes are related to bacterial virulence factors, concomitant environmental factors, host susceptibility and immune response. This review summarizes the current epidemiology of H. pylori infection in Asia and analyzes these data in the context of gastric cancer epidemiology.
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Affiliation(s)
- Kwong Ming Fock
- Division of Gastroenterology, Changi General Hospital, Singapore.
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Mbulaiteye SM, Hisada M, El-Omar EM. Helicobacter Pylori associated global gastric cancer burden. FRONT BIOSCI-LANDMRK 2009; 14:1490-504. [PMID: 19273142 PMCID: PMC2654592 DOI: 10.2741/3320] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori infection is ubiquitous, infecting close to one-half of the world's population, but its prevalence is declining in developed countries. Chronic H. pylori infection is etiologically linked to gastric adenocarcinoma, especially non-cardia type (63% of all stomach cancer or ~5.5% of the global cancer burden: ~25% of cancers associated with infectious etiology), and to gastric mucosal associated lymphoid tissue (MALT) lymphoma, which accounts for up to 8% of all non-Hodgkin lymphoma. Epidemiological, clinical, and animal studies have established a central role for H. pylori in gastric carcinogenesis and provided insights into the mechanisms and biologic relationships between bacterial infection, host genetics, nutrition, and environmental factors. These discoveries invite strategies to prevent infection to be the logical primary goals in a multi-pronged effort to curtail suffering and death from H. pylori infection-associated cancers.
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Affiliation(s)
- Sam M Mbulaiteye
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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Jafarzadeh A, Rezayati MT, Nemati M. Specific serum immunoglobulin G to H pylori and CagA in healthy children and adults (south-east of Iran). World J Gastroenterol 2007; 13:3117-21. [PMID: 17589930 PMCID: PMC4172621 DOI: 10.3748/wjg.v13.i22.3117] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the serologic IgG response to H pylori and CagA across age groups and in healthy children and adults.
METHODS: Totally, 386 children aged 1-15 years and 200 adults aged 20-60 years, were enrolled to study. The serum samples of participant were tested for presence of anti-H pylori and anti-CagA IgG by using ELISA method.
RESULTS: The seroprevalence of H pylori in adults was significantly higher than that observed in children (67.5% vs 46.6%; P < 0.000003). In children, the seropositivity rate in males (51.9%) was significantly (P < 0.05) higher than that observed in females (41.7%). The prevalence of serum anti-CagA antibody was 72.8% and 67.4% in infected children and adults, respectively. The mean titer of serum anti-CagA antibodies was significantly higher among children in comparison to adults (64.1 Uarb/mL vs 30.7; P < 0.03). In infected children and adults the prevalence of serum anti-CagA antibody was higher in males compared to females (78.4% vs 66.3%; P = 0.07 and 75.6% vs 54.71%; P < 0.04, respectively). The age-specific prevalence of anti-H pylori and anti-CagA antibody (in infected subjects) was 37.6% and 59.57% at age 1-5 years, 46.9% and 75% at age 6-10 years, 54.9% and 79.45% at age 11-15, 59.01% and 83.33% at age 20-30 years, 66.6% and 60.52% at age 31-40 years, 73.46% and 63.88% at age 41-50 years and 75.75% and 60% at age 51-60 years with mean titer of anti-CagA antibody of 75.94, 63.32, 57.11, 52.06, 23.62, 21.52 and 21.80 Uarb/mL, respectively. There was significant difference between mean serum anti-CagA antibody in age subgroups (P < 0.001).
CONCLUSION: These results showed that anti-H pylori and anti-CagA antibodies were common in the children and adults. The H pylori-specific antibodies influenced by age and sex of subjects. Moreover, it seems that males are more susceptible to infection with CagA+ strains compared to females. The seroprevalence of anti-CagA antibody was increased with age, up to 30 years and then decreased. It was also found that the magnitude of the IgG response to CagA decreased with advanced age.
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Affiliation(s)
- A Jafarzadeh
- Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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You WC, Li JY, Zhang L, Jin ML, Chang YS, Ma JL, Pan KF. Etiology and prevention of gastric cancer: a population study in a high risk area of China. ACTA ACUST UNITED AC 2006; 6:149-54. [PMID: 16246221 DOI: 10.1111/j.1443-9573.2005.00222.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
A series of studies has been carried out in Linqu County, Shandong Province, China, a high-risk area for gastric cancer, to investigate the risk factors associated with gastric cancer, precancerous lesions and the prevention of gastric cancer. Our studies showed that sour pancakes (a popular local food), salted foods, cigarette smoking, and family history of gastric cancer were risk factors, whereas fresh vegetables, and intake of vitamin C and calcium were inversely associated with the risk of gastric cancer. The prevalence of chronic atrophic gastritis was approximately 20% in an adult population in Linqu County, intestinal metaplasia was approximately 50%, and dysplasia was approximately 20%. A follow-up study showed that the relative risk of developing gastric cancer increased with the severity of gastric lesions, and was associated with dietary factors, cigarette smoking and H. pylori infection in this population. The findings strongly support the idea that gastric cancer is primarily determined by environmental factors and develops in a multistep progression of precancerous lesions.
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Affiliation(s)
- Wei Cheng You
- School of Oncology, Peking University, Beijing Cancer Hospital, Beijing Institute for Cancer Research, Beijing, China.
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Zhang L, Ma J, Pan K, Go VLW, Chen J, You WC. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter 2005; 10:139-45. [PMID: 15810945 DOI: 10.1111/j.1523-5378.2005.00301.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Helicobacter pylori infection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression of H. pylori in an endemically infected population at high risk for gastric cancer. MATERIALS AND METHODS A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 +/- 11.2 years (mean +/- SD) with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree of H. pylori infection was determined using the 13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection. RESULTS A total of 189 subjects with positive 13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative 13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05). CONCLUSIONS Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.
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Affiliation(s)
- Lian Zhang
- School of Oncology, Peking University, Beijing Institute for Cancer Research, China
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Li Z, Chen D, Zhang C, Li Y, Cao B, Ning T, Zhao Y, You W, Ke Y. HLA polymorphisms are associated with Helicobacter pylori infected gastric cancer in a high risk population, China. Immunogenetics 2005; 56:781-7. [PMID: 15650879 DOI: 10.1007/s00251-004-0723-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2004] [Revised: 08/31/2004] [Indexed: 12/29/2022]
Abstract
Helicobacter pylori is one of the most common bacterial infections associated with an increased risk of gastric cancer, but its association with host factors, particularly polymorphisms of the immune response genes, such as human leukocyte antigen (HLA) genes, is still unclear. To investigate the role of HLA polymorphisms in the risk of gastric cancer among subjects with H. pylori infection, a case-control study involving 52 gastric cancer patients and 139 non-cancer controls was conducted in Linqu County, China, an area with a high incidence of gastric cancer. Polymorphisms of HLA class I and class II alleles were determined by PCR with sequence-specific primers (PCR-SSP). The information about H. pylori infection was obtained from previous records. Among 48 class I and 19 class II HLA alleles detected in this study, two alleles, CW*03 and DRB1*01, were found to be distributed significantly differently between patients and controls [odds ratio(OR)=1.95, 95% confidence interval (CI)=1.13-3.35, P=0.017 and OR=4.39, 95% CI=1.39-13.84, P=0.012, respectively). The OR of gastric cancer risk in individuals carrying CW*03/CW*03 or CW*03/CW*N was 2.06, 95% CI=1.05-4.02, P=0.035, while the OR was 3.49, 95% CI=1.0-12.4, P=0.04 for DRB1*01/DRB1*01 or DRB1*01/DRB1*N carriers. The analysis of the interaction between H. pylori infection and HLA risk genotypes of CW*03 or DRB1*01 revealed that the effect of CW*03 and DRB1*01 genotypes on gastric cancer risk was manifested stronger in H. pylori-positive individuals (OR=5.30, 95% CI=1.73-16.29, P=0.004 and OR=13.38, 95% CI=2.52-70.98, P=0.002, respectively) than in H. pylori-negative ones (OR=1.25, 95% CI=0.25-6.12, P=0.785 and OR=2.26, 95% CI=0.18-28.88, P=0.531, respectively). The combined effect of the two risk HLA genotypes on gastric cancer risk was also analysed. The result showed that the individuals carrying both the CW*03 and DRB1*01 alleles could only be found in cancer patients (5/52), and not in controls (0/139), further suggesting that CW*03 and DRB1*01 are risk alleles advancing the progression of tumorigenesis. These observations demonstrate that host HLA genotypes may play an important role in the risk of gastric cancer, especially among persons with H. pylori infection.
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Affiliation(s)
- Zhaohui Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
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Camargo MC, Yepez MC, Ceron C, Guerrero N, Bravo LE, Correa P, Fontham ETH. Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer. Helicobacter 2004; 9:262-70. [PMID: 15165263 DOI: 10.1111/j.1083-4389.2004.00221.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Helicobacter pylori infection is usually acquired during childhood and is a known risk factor for the development of gastric malignancies in adulthood. It has been reported that early age at first infection may determine a neoplastic outcome in adults. The purpose of this study was to determine the prevalence of Helicobacter pylori infection in children residing in areas with high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate whether differences in the age of acquisition of H. pylori infection were present in the two populations. MATERIALS AND METHODS The study sample was based on a census taken in 1999. Using the (13)C-urea breath test, we compared the prevalence of H. pylori infection among children aged 1-6 years. RESULTS Among 345 children in Pasto, 206 (59.7%) were H. pylori-positive, compared with 188 (58.6%) among 321 children in Tumaco. The two populations share a common pattern of very early age at infection and marked increase in prevalence during the first 4 years of life. No differences in any one year were observed when comparing the two groups. CONCLUSIONS The prevalence of infection was similarly high and increased with age in both populations. In these populations the age of acquisition of H. pylori after 1 year of age does not appear to be a primary factor responsible for the differences in the rates of gastric cancer incidence in adults. Previous findings in adults showed lower prevalence of the most virulent genotypes in Tumaco compared to Pasto, and bacterial virulence may play a key role in determining cancer outcome.
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Affiliation(s)
- M Constanza Camargo
- Department of Pathology, Louisiana State University Health Science Center, New Orleans 70112, USA
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Saltik IN, Demir H, Engin D, Ertunç OD, Akyön Y, Koçak N. The cagA status of Helicobacter pylori isolates from dyspeptic children in Turkey. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2003; 36:147-9. [PMID: 12738384 DOI: 10.1016/s0928-8244(03)00024-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
There are inconsistent reports regarding cytotoxin-associated gene A (cagA) status of Helicobacter pylori isolates and the severity of the mucosal lesions in children. The aim of this study was to determine the prevalence of cagA(+) strains and to evaluate its correlation with clinic and endoscopic findings. We examined 45 H. pylori strains that were grown on brain-heart infusion agar supplemented with 7% horse blood. Following 72 h of incubation colonies were harvested and bacterial DNA was extracted. Polymerase chain reaction primers F1 and B1 were used to amplify a 348-bp internal fragment of cagA. The prevalence of cagA in Turkish pediatric patients was 55.6%. No association was found between cagA status and the severity of gastro-duodenal lesions.
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Affiliation(s)
- Inci Nur Saltik
- Department of Pediatrics, Section of Gastroenterology, Hacettepe University, Faculty of Medicine, 06100 Ankara, Turkey.
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Guo XL, Wang LE, Du SY, Fan CL, Li L, Wang P, Yuan Y. Association of cyclooxygenase-2 expression with Hp-cagA infection in gastric cancer. World J Gastroenterol 2003; 9:246-9. [PMID: 12532440 PMCID: PMC4611320 DOI: 10.3748/wjg.v9.i2.246] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2 expression and infection with cytotoxic-associated gene A (cagA) positive strain Helicobacter pylori (Hp) in human gastric cancer, and subsequently to provide fresh ideas for the early prevention of gastric cancer.
METHODS: 32 Specimens of gastric cancer and corresponding adjacent normal gastric mucosa were obtained from patients who had undergone surgical operations of gastric cancer. All the samples including 1 case of stomach malignant lymphoma and 31 cases of gastric adenocarcinoma were confirmed by pathology diagnosis. The expression of COX-2 in 32 specimens of gastric cancer and corresponding adjacent normal gastric mucosa was quantitatively determined and analyzed with Flow Cytometry, and the levels of COX-2 protein were compared between specimens with cagA+Hp infection and those without cagA+Hp infection. The cagA gene in 32 specimens of gastric cancer was detected by polymerase chain reaction (PCR) method.
RESULTS: Twenty-seven of 32 (84%) specimens of gastric cancer showed over-expression of COX-2, compared with the adjacent normal gastric mucosa. cagA+ gene were detected from 19 specimens of gastric cancer, but not from the other 13 specimens. The levels of COX-2 protein in 19 specimens of gastric cancer with cagA+Hp infection (the number of positive cells was 73.82 ± 18.2) were significantly higher than those in the 13 specimens without cagA+Hp infection (the number of positive cells was 35.92 ± 22.1).
CONCLUSION: COX-2 is overexpressed in gastric cancer and cagA+Hp infection could up-regulate the expression of COX-2 in gastric cancer in human. There may also exist another way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA+Hp infection. Therefore, applying COX-2 selective inhibitors could be an effective and promising way to prevent gastric cancer.
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Affiliation(s)
- Xiao-Lin Guo
- Cancer Institute, the First Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
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Abstract
There have been no major breakthroughs in the field of epidemiology and diagnosis of Helicobacter pylori infection over the last year, thus for this reason, these two topics will be treated in the same chapter. Information on the incidence of infection, as in the study of Malaty et al. are now being published from long-term cohort follow-ups. The route of transmission of H. pylori remains controversial, with circumstantial evidence for infection via exposure to animals, contaminated water supplies and oral reservoirs being reported. The value of citric acid to improve urea breath test (UBT) results has been documented. A novel stool test has been released on the market and we are awaiting more information, while detection of antibodies in urine gave satisfactory results. However, the most interesting data comes from the study of McColl et al. who clearly proved on a large sample and a 1-year follow-up that the 'test and treat' strategy using UBT, as proposed in the Maastricht Consensus Report, is definitely the method to use.
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Affiliation(s)
- Hazel Mitchell
- School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, Australia
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