Helicobacter Pylori and Gastric Cancer

Helicobacter pylori has been the subject of intense investigation since its culture from a gastric biopsy in 1982.From the beginning, this gram-negative bacterium has provoked the interest of bacteriologists, gastroenterologists,infectious disease specialists, cancer biologists, epidemiologists, pathologists, and pharmaceutical scientists.Pathologists were among the first groups of scientists to reevaluate their data in the context of the newlydiscovered bacterial etiological agent. Chronic inflammation elicited by the bacterium provided the missing linkin the progression to gastric carcinoma; accordingly, H. pylori was named as a class 1 carcinogen by the WorldHealth Organization. Two key papers published in 1991 in the Journal of the National Cancer Institute reporteda positive association between gastric cancer and H. pylori infection. This fact provided a strong rationale to treatall who tested positive for H. pylori. Antibiotic regimens have been largely successful, but some agents such asmetronidazole and clarithromycin have been rendered ineffective in several countries and geographical areas ofthe United States by the emergence of strains resistant to these compounds. Although there was some skepticisminitially, within few years numerous research groups verified the association of H.pylori with gastric carcinoma.Host related factors for the development of disease can indicate genetic susceptibility (or resistance) or acquiredinfluences, which may stimulate defenses of the host against environmental carcinogens like H.pylori. The presentarticle is a mini-review of the history and epidemiology of the bacterium and its suggested association with thedevelopment and progression of gastric cancer.     

白细胞介素-1B 基因多态性、幽门螺杆菌感染与胃癌发生的相关性

目的 探讨湖南衡阳地区白细胞介素-1B（IL-1B）基因多态性与胃癌的关系以及幽门螺杆菌（Helicobacter pylori,HP）感染后胃癌发生的易感基因型。方法 52例胃癌患者癌旁正常胃粘膜组织和55例慢性胃炎患者胃粘膜组织,均经快速尿素酶和PCR检测HP,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术,进行基因型检测,并对C/C、T/T进行测序,比较各基因型在胃癌组和胃炎组中的分布差异。结果 IL-1B-31T、IL-1B-511T等位基因和IL-1B-31T/T、IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为1.97（95%CI=1.15-3.59）、2.52（95%CI=1.45-4.39）和2.71（95%CI=1.10-6.66）、3.33（95%CI=1.14-9.73）。在伴有HP感染的群体中进行比较,IL-1B-31位点各基因型未见明显差异;但IL-1B-511T等位基因和IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为2.16（95%CI=1.10-4.23）和3.43（95%CI=1.01-11.62）。结论 在湖南衡阳地区IL-1B-31T/T、IL-1B-511T/T基因型与胃癌发病风险相关,在HP被感染后IL-1B-511T/T基因型可能为湖南衡阳地区胃癌易感基因型。     

白细胞介素-1B 基因多态性、幽门螺杆菌感染与胃癌发生的相关性

 目的 探讨湖南衡阳地区白细胞介素-1B（IL-1B）基因多态性与胃癌的关系以及幽门螺杆菌（Helicobacter pylori,HP）感染后胃癌发生的易感基因型。方法 52例胃癌患者癌旁正常胃粘膜组织和55例慢性胃炎患者胃粘膜组织,均经快速尿素酶和PCR检测HP,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术,进行基因型检测,并对C/C、T/T进行测序,比较各基因型在胃癌组和胃炎组中的分布差异。结果 IL-1B-31T、IL-1B-511T等位基因和IL-1B-31T/T、IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为1.97（95%CI=1.15-3.59）、2.52（95%CI=1.45-4.39）和2.71（95%CI=1.10-6.66）、3.33（95%CI=1.14-9.73）。在伴有HP感染的群体中进行比较,IL-1B-31位点各基因型未见明显差异;但IL-1B-511T等位基因和IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为2.16（95%CI=1.10-4.23）和3.43（95%CI=1.01-11.62）。结论 在湖南衡阳地区IL-1B-31T/T、IL-1B-511T/T基因型与胃癌发病风险相关,在HP被感染后IL-1B-511T/T基因型可能为湖南衡阳地区胃癌易感基因型。     

The COX-2 -765 G>C Polymorphism is Associated with Increased Risk of Gastric Carcinogenesis in the Chinese Hui Ethnic Population

Background: The Chinese Hui ethnic group has diverse origins, including Arab, Persian, Central Asian,and Mongol. The standardized mortality rate of gastric cancer in the Hui population is higher than the overallChinese population. In this study, we investigated whether COX-2-765G>C polymorphism, an extensively studiedpolymorphism, contributes to gastric cancer and its precursor lesions (GPL) in the Chinese Hui ethnic group.Materials and Methods: COX-2-765G>C polymorphism was determined by pyrosequencing in 100 gastriccancer cases, 102 gastric cancerand its precursor lesions cases and 105 controls. Data were statistically analyzedusing Chi-square tests and logistic regression models. Results: Among the Chinese Hui ethnic group COX-2-765 C allele carriers were at increased risk for gastric cancer (OR=1.977, 95%CI=1.104-3.541). We also foundan interaction between COX-2 -765 C carriers and Helicobacter pylori infection and eating pickled vegetables.Conclusions: Our findings suggest a multi-step process of gene-environment interaction contributes to gastriccarcinogenesis.     

幽门螺杆菌致胃癌相关因素研究进展

幽门螺杆菌已被世界卫生组织国际癌症研究机构列为胃癌的第一类致癌物.虽然全世界超过半数人口感染幽门螺杆菌,但最终发展为胃腺癌者仅占感染人群的1％～3％.近年来的观点认为,胃癌是一种感染性疾病,毒力因子、宿主遗传因素和环境因素共同影响着幽门螺杆菌的致胃癌作用.其中,毒力因子在致胃癌初始发生的相关免疫反应中起重要作用,宿主遗传因素可影响炎性反应的严重度并可能加重胃黏膜损伤,而环境因素则可能改变幽门螺杆菌感染的临床结局.本文就幽门螺杆菌致胃癌相关因素的最新研究进展进行综述.     

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generationof aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotidepolymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastriccancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophyand 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqmanassay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Oddsratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Amonghealthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype,compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significantcorrelation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition,no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions:This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk ofH. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require furtherinvestigation.     

Role of interleukin polymorphisms in gastric cancer: "Pros and cons"

Helicobacter pylori (H. pylori) infection is the leading cause of gastric cancer worldwide. Infection with this bacterium causes a chronic active immune response that persists for the life of the host. The combination of bacterial factors, environmental insults, and the host immune response drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward GC. Among the host factors, IL-1 gene cluster polymorphisms (IL-1B encoding IL-1β and IL-1RN encoding IL-1ra, its naturally occurring receptor antagonist) play a decisive role in modulating the risk of developing hypochlorhydria, gastric atrophy and GC in the presence of H. pylori infection. In particular, one single nucleotide polymorphism in the IL-1B promoter (IL-1B-511C⁄T), and the short allele of a 86-bp variable number of tandem repeats polymorphism in the IL-1RN second intron (IL-1RN*2) are associated with an increased risk for GC. However this hypothesis is still to be fully confirmed. This review focuses on the divergent results obtained by several epidemiological and functional in vitro and in vivo studies and show that IL-1 genotyping has still no role in the clinical management of patients with H. pylori infection.     

Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions

Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helicobacter pylori (H. pylori) infection (e.g. TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epidemiological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymorphisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.     

胃癌患者Hp感染及血清GPDA活性的变化

目的探讨胃癌患者粪便Hp检出率与血清GPDA活性变化的关系。方法利用幽门螺旋杆菌粪便抗原检测法(HpSA法)和速率法分别检测117例初治前胃癌患者、45例良性胃部疾病患者及40例正常人粪便中的Hp阳性率和血清GPDA活性并作相关分析。结果胃癌患者Hp感染率及其血清GPDA的阳性率分别为70.1%和71.5%,显著高于良性胃部疾病患者和正常人(P<0.01)。胃癌的部位与Hp感染有关(P<0.05),而其血清GPDA活性与临床各因素的关系并不密切(P>0.05),两者无相关性(P>0.01)。结论Hp感染可能与胃癌的发生、发展有关,血清GPDA检测对胃癌的诊断有一定的意义。     

Helicobacter Pylori Eradication as a Preventive Tool Against Gastric Cancer

Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric ‍cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a ‍treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational ‍studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer ‍patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, ‍976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori ‍eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in ‍China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal ‍metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates ‍of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be ‍12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected ‍Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for ‍infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are ‍infected among those exposed and the knowledge that only a small percentage of individuals infected with the ‍bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such ‍interactions should provide useful information for anti-H. pylori preventive strategies.     

上消化道癌高低发区幽门螺旋杆菌感染与胃癌

目的：研究江苏上消化道癌高发区淮安市、低发区邳州市幽门螺旋杆菌（Ｈｐ）感染与胃癌发生的关系。方法：用酶联免疫法及乳胶凝集法检测７９例胃癌、７７例食管癌、１５６例患者亲属和１００名一般居民对照者血浆中Ｈｐ抗体,结果：低发区胃癌患者组Ｈｐ感染率（６６．６７％）显著高于发区（３８．６４％）,两地区其他组之间Ｈｐ感染率无显著差异,低发区ＨＰ感染者胃癌的危险性显著升高（ＯＲ３．６１,９５％ＣＩ１．０１－１２     

Early-onset gastric cancer: Learning lessons from the young

There is by no means a clear-cut pattern of mutations contributing to gastric cancers, and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer, such as Helicobacter pylori infection, diet, ageing and other environmental factors. Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship. It is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOGC) than in gastric cancers found in older patients as they have less exposure to environmental carcinogens. EOGC, therefore, could provide a key to unravelling the genetic changes in gastric carcinogenesis. Gastric cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric carcinogenesis. This review summarizes the literature regarding EOGC and also presents evidence that these cancers have a unique molecular-genetic phenotype, distinct from conventional gastric cancer.     

幽门螺杆菌感染与胃癌及癌前病变的环氧合酶-2表达的研究

目的：通过研究HP感染与胃癌及癌前病变中环氧合酶－2（cox-2)表达的关系,以探讨HP可能的致癌机制。方法：经胃镜和病理诊断明确的病例共120例,包括慢性浅表性胃炎（CSG）,肠上皮化生,不典型增生,胃癌各30例,以ABC免疫组化法检测上述标本的cox-2,以改良Giemsa法检测HP,结果：胃癌组肠型胃癌HP阳性率为83．3％（20／24）,弥漫型6型中HP阳性1例,胃癌HP阳性率为与CSG比较差异非常显著（P＜0．01）,肠型胃癌HP阳性率与胃癌阳性率比较有明显差异（P＜0．05）,各组HP阳性的cox-2与其HP阴性者作相应比较均有显著或非常显著性差异（P＜0．05或P＜0．01）,结论：HP感染可使胃粘膜中cox-2过度表达,导致细胞凋亡受抑制,从而可引起胃癌的发生。     

胃癌组织ras 基因突变及其与幽门螺杆菌感染的关系

 目的　初步探讨胃癌组织中 ras基因突变与幽门螺杆菌 ( Helicobacter pylori,Hp)感染的关系。方法　 43例胃癌组织新鲜标本及相应血清标本纳入研究。用 PCR- RFLP法测定 ras基因 1 2密码子的突变 ;用血清学方法检测 Hp的感染状况。结果　 43例胃癌中有 2 8例存在 ras基因1 2密码子的突变 ,突变率为 65 .1 2 % ;43例胃癌中 ,Hp阳性 30例 ,阳性率为 69.77% ,其中 Cag A阳性 2 4例 ,阳性率为 80 % ;30例 Hp阳性的胃癌中 ,有 1 9例发生 ras基因 1 2密码子的突变 ,发生率为 63.33% ,1 3例 Hp阴性的胃癌中 ,有 9例发生 ras基因 1 2密码的突变 ,发生率为 69.2 3% ,二者比较无明显差异 ( P>0 .0 5 )。结论　 ras基因 1 2密码子的突变可能与胃癌的发生有关 ,胃癌中ras基因 1 2密码子的突变与 Hp及 Cag A阳性的 Hp感染无明显相关性 ,Hp感染可能不是其改变的唯一或必须因素.     

胃癌与肿瘤微环境的研究进展

胃癌（Gastriccarcinoma,GC）的发病率居全世界恶性肿瘤的第四位,死亡率居第二位。尽管胃癌的发病率在过去的几十年里有所下降,但它仍然是一个严重危害健康的问题。肿瘤微环境在肿瘤的发生和进展中有重要作用,主要包括肿瘤相关的巨噬细胞、淋巴细胞、癌相关成纤维细胞、血管生成因子、细胞因子、肿瘤微环境以及它们作用机制的信号趋化因子等。本文就肿瘤微环境与胃癌相关性的研究进展综述如下。     

解放军总医院胃癌住院患者临床资料分析

目的 总结近一年以来胃癌住院患者临床资料特点、变化趋势,对比各项检查结果针对性筛查幽门螺杆菌感染患者,研究与胃癌患病的关系.方法 回顾性分析经病理诊断并收治入院的胃癌患者(共计1461例),对其平均年龄、性别比例、病理类型、发生部位、TNM分期等进行统计;二筛选病例资料里幽门螺杆菌感染检测患者(共265例),对这类患者...     

p53基因在幽门螺杆菌致胃癌机制中的作用

为了探讨Ｈｐ 感染在胃癌及癌前病变中的作用机制,应用分子生物学方法检测胃粘膜标本中ｐ５３ 基因点突变情况。结果显示, Ｈｐ 阳性患者ｐ５３ 基因的突变发生率明显高于Ｈｐ 阴性者;胃癌组Ｈｐ 阳性患者中ｐ５３ 的突变率显著高于阴性者。结果表明,Ｈｐ 的感染可能与胃癌的发生有关,基因突变可能是Ｈｐ 致胃癌的作用机制之一。     

Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer

Background. The development of a second primary cancer in the gastric remnant after gastrectomy for early gastric carcinoma is a problem, and eradication of Helicobacter pylori after the operation has been recommended. However, to date, practical indications for H. pylori eradication after gastric cancer surgery have not yet been reported. Methods. We examined H. pylori infection in the gastric remnant after distal gastrectomy for primary gastric cancer. One hundred and nine patients who had had a gastrectomy were studied. Endoscopic findings and results from the urease test, bacteriologic assessment, serological test, and histopathological examination were analyzed. Results. Seventy-one patients (65.1%) were judged to be positive for H. pylori infection. The prevalence of H. pylori infection was found to be significantly decreased in older patients, patients in whom the operation had been performed a long time before examination, patients with symptoms, and patients with severe reflux gastritis. On the other hand, histologically, chronic and acute gastritis correlated significantly with H. pylori infection. H. pylori prevalence was highest in mildly atrophic mucosa and decreased with more extensive atrophic changes of the mucosa. Conclusions. The persistence of H. pylori -related active gastritis in the gastric remnant after gastric cancer surgery was suggested in younger patients with mild atrophic gastritis and without reflux gastritis. These patients may be the best candidates for H. pylori eradication therapy. Received: April 13, 2001 / Accepted: June 18, 2001