Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.     

幽门螺杆菌感染、十二指肠溃疡及家族史与胃癌发生的相关性

目的 探讨幽门螺杆菌感染、十二指肠溃疡以及家族史与胃癌发病的相关性.方法 选取256例胃癌患者均为随访时仍存活的新发病例.分析幽门螺旋杆菌感染、十二指肠溃疡及家族史与胃癌发生的相关性.结果 共调查128对.本研究中胃癌家族史即病例组和对照组研究对象的一级亲属(父母、兄弟姐妹、子女)中有胃癌患者.有胃癌家族史的比例为23.39%,显著高于对照组(15.62%)(P=0.045).对变量进行Logistic回归分析,Hp阳性和十二指肠溃疡与胃癌的发生相关(P<0.05).结论 Hp感染及十二指肠溃疡是胃癌危险因素中的显著危险因子.     

老年患者的幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C-erbB-2基因表达

目的探讨老年患者幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C．erbB-2基因表达及其临床意义。方法分析老年患者的胃镜检查活检标本116例,HE染色观察胃黏膜的炎症和异型增生变化,特染法检测胃黏膜的肠上皮化生,应用Warthin-stary银染色法检测HP,应用ELISA法检测血清学HPIgG,14C尿素呼气试验（14C-UBT）检测HP,应用免疫组化sP法检测C-myc、p16、p53、K-ras和C-erbB-2基因的表达。结果老年患者在不同胃组织中C-myc、p16、p53基因的表达均有显著差异,而K-ras和C-erbB-2基因表达未见显著性差异。HP感染率以胃癌为最高,其次为胃溃疡。结论本实验通过老年患者的HP检测和观察胃黏膜的炎症和异型增生变化,再结合癌基因和抑癌基因的表达异常,提示萎缩性胃炎异型增生、肠上皮化生和胃癌的HP感染率均高于非萎缩性胃炎。再次表明胃癌与HP感染有一定相关性。     

幽门螺杆菌感染与胃癌细胞侵袭转移的关系研究

目的探讨幽门螺杆菌(H.pylori)感染与胃癌细胞侵袭转移的关系及可能机制。方法将幽门螺杆菌与胃癌细胞株SGC7901共培养12 h;按胃癌细胞与H.pylori菌落之比为1∶100,与SGC7901共培养0、12、24 h来进行Western-blot实验,测定基质金属蛋白酶9(MMP-9)、细胞外总调节蛋白激酶1/2(t-ERK1/2)、磷酸化细胞外调节蛋白激酶1/2(p-ERK1/2)在胃癌细胞中表达水平的变化;共培养24 h后,分为两组,不处理组和加入ERK抑制剂U0126的处理组,应用Transwell小室细胞侵袭实验,比较抑制ERK前后对胃癌细胞运动、侵袭能力的影响。结果随着胃癌细胞与H.pylori比例增大,胃癌细胞中MMP-9、p-ERK1/2表达明显增高(P<0.01),t-ERK1/2表达水平无明显差异(P>0.05)。不处理组胃癌细胞穿透基膜的数量与H.pylori比例呈正相关,而U0126处理组的胃癌细胞穿透基膜数量明显减少。各组之间的差异有统计学意义(P<0.01)。结论幽门螺杆菌感染能促进胃癌细胞的侵袭迁移能力,可能与其通过ERK信号途径增强MMP-9表达而诱导胃癌的发生发展有关。     

家族性胃癌遗传学研究进展

遗传性弥漫型胃癌与钙黏蛋白基因的种系突变有关,约占家族性胃癌病例的1/3。其他2/3不符合遗传性弥漫型胃癌诊断标准的家族性胃癌依然缺乏明确的分子诊断依据。目前根据钙黏蛋白基因预测情况预防性切除相关家族性胃癌,只在一部分遗传性弥漫型胃癌中有临床意义。     

胃癌及癌前病变与幽门螺杆菌感染相关性的临床分析

目的:测定幽门螺杆菌在萎缩肠化生胃炎,异型增生及胃癌中感染情况,探讨Hp与它们的相关性。方法:萎缩肠化生胃炎(A组)患者342例,异型增生(B组)229例,胃癌患者(C组)298例,采用Hp抗体ELISA法检测血清抗Hp-IgG抗体。结果:肠化生患者较非肠化生胃黏膜中的Hp感染多见。异型增生和胃癌的Hp感染率均高于萎缩性胃炎组(P<0.05),异型增生和胃癌两者间的Hp感染率亦存在差异(P<0.05)。幽门螺杆菌感染的萎缩肠化生胃炎及异性增生较非幽门螺杆菌感染者发生癌变的差异性显著,P<0.05;幽门螺杆菌感染的胃癌5年生存期显著短于非感染者,P<0.05。结论:Hp感染与萎缩肠化生胃炎,异型增生及胃癌有密切相关性,并缩短萎缩肠化生胃炎,异型增生癌变时间,缩短胃癌5年生存时间。     

胃癌、不典型增生及慢性胃炎与幽门螺杆菌L型感染关系的研究

 目的　探讨幽门螺杆菌L型 (Hp L型 )感染与胃癌、不典型增生及慢性胃炎的关系。 方法　用组织切片革兰染色和免疫组化染色法 ,对 36例胃癌、34例不典型增生、4 2例慢性胃炎及 15例正常胃黏膜进行Hp L型检测。 结果　胃癌、不典型增生及慢性胃炎的Hp L型检出率分别为 80 .6 %、79.4 %和 73.8% ,其阳性率之间无显著性差异 (P >0 .0 5 ) ,且均高于正常胃黏膜 (P <0 .0 5 )。结论　Hp L型感染与胃癌、不典型增生及慢性胃炎关系密切 ,并在胃癌的发生中起一定作用。     

Gastric Cancer in Asian American Populations: a Neglected Health Disparity

Gastric cancer incidence rates vary dramatically by world region with East Asia having the highest rate. TheAsian population of the United States (US) is growing rapidly and over 17 million Americans are of Asian descent.A majority of Chinese, Korean and Vietnamese Americans are immigrants. Americans of East and SoutheastAsian descent experience marked gastric cancer disparities and the incidence rate among Korean men in the USis over five times higher than the incidence rate among non-Hispanic white men. Randomized controlled trialshave provided evidence for the effectiveness of helicobacter pylori identification and eradication in preventinggastric cancer. Additionally, Japan and South Korea have both experienced improvements in gastric cancermortality following the implementation of programs to detect early stage gastric cancers. There are currently noclear US guidelines regarding the primary and secondary prevention of gastric cancer in high-risk immigrantpopulations. However, it is likely that a proportion of US physicians are already recommending gastric cancerscreening for Asian patients and some Asian immigrants to the US may be completing screening for gastriccancer in their native countries. Surveys of US primary care physicians and Asian American communities shouldbe conducted to assess current provider practices and patient uptake with respect to gastric cancer preventionand control. In the absence of clinical guidelines, US health care providers who serve high-risk Asian groupscould consider a shared decision-making approach to helicobacter pylori identification and eradication, as wellas gastric endoscopy.     

血清微量元素、GPDA活性和Hp感染与胃癌发生的相关性

目的探讨血清微量元素、苷氨酰脯氮酸二肽氮基肽酶活性（GPDA）和幽门螺杆菌（Hp）感染与胃癌发生的关系。方法采用幽门螺杆菌粪便抗原检测法（HpSA法）、终点法和速率法，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阳性率和血清微量元素Ca、Mg、Fe、Cu、Zn的含量及GPDA活性，并比较分析。结果胃癌患者血清Fe和Cu／zn含量明显高于正常对照组（均P〈0．05），Zn含量显著低于正常对照组（P〈0．05），Hp和GPDA阳性率分别为70．9％（83／117）和71．8%（84／117）。Hp、GPDA阳性组Zn含量显著低于阴性组（P〈0．05）。结论血清Zn含量降低可能是胃癌发生的癌前因素，Zn含量降低可诱发Hp感染而促发癌变。     

幽门螺旋杆菌与肝癌相关性的研究进展

幽门螺旋杆菌被认为是胃炎、消化性溃疡、胃癌的主要致病因素,然而近年来,诸多实验研究指出它还与肝脏肿瘤之间有密切联系,现就近几年的相关研究进展进行综述,主要涉及侵袭肝脏途径、入侵肝脏细胞病理机制与肝炎肝硬化的关系等方面。