H pylori and gastric cancer： Shifting the global burden

INTRODUCTION Since the discovery of H pylori in 1983, intensive research has led to the conclusion that infection with this bacterium is the major cause for the development of distal gastric cancer. Infection with the bacterium leads to a chronic inflamma…     

Eradication of H pylori for the prevention of gastric cancer

Infection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patients at risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.     

Diet, Hpylori infection and gastric cancer： Evidence and controversies

Despite decreasing incidence and mortality rates, gastric cancer (GC) still remains the fourth most common cancer and the second most common cause of cancer-related deaths worldwide. Due to the limited treatment options, at present, prevention is likely to be the only effective means of controlling this disease. The success of a prevention strategy depends upon the understanding of etiological and pathogenic mechanisms underlying gastric carcinogenesis. The etiology of GC is multi-factorial, however, in the recent years, mounting evidence suggests that environmental factors play a key role. The most important environmental factors implicated in the pathogenesis of GC are diet and H pylori infection. Thus, modifications in lifestyle and dietary habit associated with eradication of H pylori infection could hypothetically represent the most promising potential targets for GC prevention. In this review we will address the evidence and the controversies on the role of these agents in noncardia GC by focusing on retrospective and prospective observational studies and interventional trials.     

三叶因子1与胃癌关系研究进展

三叶因子1(TFF1)属三叶因子家族,是近年来被人们注意到的具有胃肠道粘膜保护及修复作用的生长因子类小分子多肽物质。其基因现已被认为是一个重要的胃癌抑癌基因。现就三叶因子1的结构、功能、分布、表达及其与胃癌关系的研究进展作一综述。     

Evaluation of the role of H pylori infection in pathogenesis of gastric cancer by immunoblot assay

INTRODUCTION H pylori, a Gram-negative bacterium, is now widely considered as one of the major etiologic factors in the pathogenesis of a great variety of gastrointestinal diseases such as gastritis, peptic ulcers and mucosa- associated lymphoid tissue ly…     

慢性胃炎、胃癌组织中幽门螺杆菌基因分型的临床研究

目的 探讨幽门螺杆菌(HP)基因分型与慢性胃炎、胃癌的关系。方法 应用PCR—RFLP方法对36例慢性胃炎及45例胃癌组织中的幽门螺杆菌菌株进行检测。并用HindⅡ酶切尿毒酶B(UreB)扩增基因产物进行多态性分析。结果 36例慢性胃炎HP阳性24例(66．7％),45例胃癌组织中HP阳性23例(51．1％)。二者差异无显著性。47例HP阳性标本均显示不同的RFLP图谱。胃癌组织中未发现特异性条带。结论 慢性胃炎、胃癌与HP感染密切相关。HP基因具有多态性,HP菌株存在基因型差异。PCR—RFLP方法可对HP菌株进行鉴定并将其分型。     

Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases

AIM: To investigate the relationship between the expression of pepsinogen C (PGC) and gastric cancer, precancerous diseases, and Helicobacter pylori (H pylori) infection. METHODS: The expression of PGC was determined by immunohistochemistry method in 430 cases of gastric mucosa. H3 Pylori infection was determined by HE staining, PCR and ELISA in 318 specimens. RESULTS: The positive rate of PGC expression in 54 cases of normal gastric mucosa was 100%. The positive rates of PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic gastritis or gastric dysplasia and gastric cancer decreased significantly in sequence (P<0.05; 100%/89.2% vs 14.3%/15.2% vs 2.4%). The over-expression rate of PGC in group of superficial gastritis with H pyloriinfection was higher than that in group without H pylori infection (P<0.05; x2= 0.032 28/33 vs 15/25). The positive rate of PGC expression in group of atrophic gastritis with H pylori infection was lower than that in group without H pylori infection (P<0.01; x2 = 0.003 4/61 vs9/30), and in dysplasia and gastric cancer. CONCLUSION: The level of PGC expression has a close relationship with the degree of malignancy of gastric mucosa and development of gastric lesions. There is a relationship between H pylori infection and expression of antigen PGC in gastric mucosa, the positive rate of PGC expression increases in early stage of gastric lesions with H pylori infection such as gastric inflammation and decreases during the late stage such as precancerous diseases and gastric cancer. PGC-negative cases with H py/ori-positive gastric lesions should be given special attention.     

幽门螺旋杆菌与残胃癌发生的研究进展

残胃癌发病率呈上升趋势,其发生机制与多种因素有关,其中幽门螺旋杆菌感染被认为是重要因素,但尚无肯定的结论.本文就残胃幽门螺旋杆菌感染与残胃癌发生及相关机制作一综述.     

Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer

AIM: To study the expression of trefoil factor 1 (TFF1) and TFF2 in precancerous condition and gastric cancer and to explore the relationship between TFFs and tumorigenesis, precancerous condition and gastric cancer. METHODS: The expression of TFF1 and TFF2 was immunohistochemically analyzed in paraffin-embedded samples from 140 patients including 35 cases of chronic superficial gastritis (CSG), 35 cases of gastric ulcer (GU), 35 cases of chronic atrophic gastritis (CAG) and 35 cases of gastric cancer (GC). RESULTS: TFF1 and TFF2 were located in cytoplasm of gastric mucous cells. In CSG, GU, CAG and GC, the level of TFF1 expression had a decreased tendency (P<0.05). The expression of TFF2 was higher in GU than in CSG, but the difference was not significant. The expression of TFF2 also had a decreased tendency in GU, CAG, and GC (P<0.05). CONCLUSION: The reduced expression of TFF1 and TFF2 in precancerous conditions and gastric cancer may be associated with the proliferation and malignant transformation of gastric mucosa. More investigations are needed to explore the mechanism of TFFs and the relationship between TFFs and gastric cancer.     

Prevalence of H pylori associated ‘high risk gastritis＇ for development of gastric cancer in patients with normal endoscopic findings

AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper-GI endoscopy. METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems. RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development--only a proper follow-up can provide this information.     

胃癌及癌前病变组织三叶因子3表达的相关性研究

目的检测三叶因子3（TFF3）在胃癌前病变及胃癌的表达,探讨TFF3的表达与胃癌发生、发展的关系。方法收集慢性浅表性胃炎（CSG）,慢性萎缩性胃炎伴中、重度肠上皮化生（IM）,慢性萎缩性胃炎伴中重度不典型增生（Dys）患者各30例,胃癌（GC）患者40例采用SP免疫组化法检测TFF3蛋白的表达。结果CSG、IM、Dys、GC组织中TFF3表达呈逐渐增强趋势,差异具有统计学意义（P〈0.05）。结论TFF3表达在胃癌发生、发展过程中起一定作用。     

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 microg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group (H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9+/-13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.     

幽门螺杆菌致胃癌发生机制

幽门螺杆菌（Helicobacter pylori，简称Hpylori或HP）是全球范围内高感染率的慢性感染性致病菌，全世界有50％以上的人口感染本菌，在发展中国家感染率更高，我国在80％左右。大量的流行病学资料调查表明，H．pylori除了是消化性溃疡的最主要病因外，也是胃腺癌和胃淋巴组织相关淋巴瘤发生的主要原因，研究显示由该菌引起的炎症可导致萎缩性胃炎，肠上皮化生，不典型增生，最终演变为胃腺癌，1994年国际癌症研究中心将其列为第一类致癌因子。胃癌是人类发生的最常见的恶性肿瘤之一，其致死率位居恶性肿瘤第二。我国在上个世纪进行的两次全国普查表明，其死亡率在我国居第一位。胃癌多发于50岁以上，日本、韩国、哥伦比亚和我国是胃癌的高发国家。在胃恶性肿瘤中，腺癌约占85％～95％。尽管胃腺癌的发病机制还不清楚，但与H．pylori的长期定植、遗传因子和环境有关。     

Causal role of Helicobacter pylori infection in gastric cancer

Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori(H pylori) is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of H pylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.     

白细胞介素-6与胃癌易感性的相关研究

目的评价IL-6 174G/C和IL-6 572G/C基因多态性与胃癌风险的相关关系,以及IL-6基因多态性与幽门螺杆菌(H.pylori)感染和吸烟的交互作用。方法采用病例对照研究方法,纳入咸宁市中心医院消化内科2008年1月-2011年5月新发胃癌246例,非肿瘤患者274例作为对照组。采用PCR-RFLP方法测定IL-6 174G/C和IL-6 572G/C的基因分型。结果研究发现携带IL-6 174CC基因型和C等位基因型胃癌发病风险显著增高,调整后的OR(95%CI)分别为1.88(1.07~3.48)和1.56(1.14~2.52)。携带IL-6 174GC和CC基因型在H.pylori阳性感染者中和吸烟者中均能增加患胃癌的风险,IL-6 174G/C基因多态性与H.pylori感染有交互作用(P0.05)。研究未发现IL-6 572G/C基因多态性与胃癌发病风险有相关关系。结论本研究结果表明IL-6基因多态性具有促进胃癌发生和发展的作用,IL-6可以作为胃癌遗传学的检测指标,用于检验胃癌易感个体的生物学指标。     

Increased expression of cyclooxygenase-2 in first-degree relatives of gastric cancer patients

AIM: To study the expression of cydooxygenase-2 (COX-2) in human gastric cancer tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum and corpus of the first-degree relatives of the recruited cancer patients. METHODS: The expression of COX-2 mRNA in 38 patients with gastric cancer and their 29 first-degree relatives and 18 healthy controls was assessed by the real time RT-PCR. The expression of COX-2 protein was determined by Western blot. RESULTS: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%) cancerous tissues compared to their respective paired normal mucosa (P<0.001). Interestingly, increased COX-2 mRNA expression was also found in mucosa of the corpus (6/29) and antrum (13/29) of their first-degree relatives. Increased COX-2 mRNA expression was more frequently observed in the antrum biopsies from cancer patients than in the antrum biopsies from healthy controls (P<0.05). In addition, 3 of 23 (13%) patients with atrophic mucosa and 6 of 35 (17%) patients with intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2 expression increased in H pylori-positive tissues, especially in antrum mucosa. CONCLUSION: Increased COX-2 expression is involved in gastric carcinogenesis, and may be necessary for maintenance of the malignant phenotype and contribute to Helicobacter pylori-associated malignant transformation.     

A global burden of gastric cancer: the major impact of China

Introduction: 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.     

H pylori stimulates proliferation of gastric cancer cells through activating mitogen-activated protein kinase cascade

INTRODUCTION H pylori is an important pathogen associated with gastritis and peptic ulcers[1]. It has also been defined as a carcinogen[2]. The mechanisms of pathogenic and carcinogenic effects of H pylori infection are under intensive investigation. Rese…     

No relationship between IL-1B gene polymorphism and gastric acid secretion in younger healthy volunteers

AIM: To investigate the influence of IL-1B-511 gene polymorphism on IL-1B mRNA expression and gastric acid output in individual with or without Helicobacter pylori (H pylori) infection. METHODS: IL-1B mRNA expression and gastric acid secretion in 117 health volunteers were assayed using semi-quantitative RT-PCR and gastric juice assay, respectively. Pepsinogen (PG) Ⅰ and Ⅱ of 255 subjects (including 117 health volunteers) were also examined. RESULTS: T/T genotype individuals with H pylori infection had a more decreased PG Ⅰ/Ⅱ ratio. In gastric antrum mucosa, the individuals with H pylori infection had higher IL-1B expression than those without H pylori infection, but there was no obvious difference among each genotype. In gastric corpus, the individuals with H pylori infection had a significantly higher IL-1B expression than those without H pylori infection. IL-1B-511T/T genotype was markedly higher as compared with the other two genotypes. Both maximal acid output and basic acid output were similar among each genotype in IL-1B-511 gene locus, regardless of H pylori infection. CONCLUSION: IL-1B-511 T allele does not decrease gastric acid output, although it has a stimulated influence on IL-1B expression. Consequently, the pathway, through which IL-1B plays a central role in gastric cancer development, might not depend on low acid, but on the other regulation mechanisms.     

白细胞介素-1B基因多态性分布与胃癌易感性的相关性研究

目的 研究白细胞介素-1B(IL-IB)基因多态性与胃癌间的相关性,建立本地区IL-1B基因多态性正常分布。方法 应用基因芯片测定了54例济南地区正常人群中IL-1B基因启动子区域内-31(T-C转换)和-511(C-T转换)位点多态性。结果 本组-31CC、-31CT、-31TT和-31C携带者出现的频率分别为27％、70％、3％和97％;-511CC、-511CT、-511TT和-511T携带者出现的频率分别为39％、35％、26％和60％;-31CC／-511TT基因频率(14．5％)高于-31TT／-511CC基因频率(5％)。结论 不同地区和不同种族间IL-1B-31和-511位点多态性分布存在差别,这种差别与不同地区和种族间胃癌的易感性相关。