食管癌P53基因第5外显子突变分析

目的　分析不同地区食管癌组织中 p5 3基因第 5外显子的突变谱。 方法　采用PCR扩增产物纯化后直接DNA序列测定技术对陕西省西安市 4 2例和河南省林州市 4 3例食管癌标本 p5 3基因第 5外显子突变情况进行检测。结果　西安和林州市食管癌标本中 p5 3基因第 5外显子突变率分别为 14 3% (6 /42 )和 18 6 % (9/43) ,两地突变率比较差异无统计学意义 (P >0 0 5 )。西安 6个突变位点中 4个为点突变 ,2个为缺失突变 ;林州 10个突变位点中9个为点突变 ,1个为插入突变。西安市有 4例突变发生在 12 6～ 12 8位点 ,林州市仅有 2例发生在该区域 (2 /10 ) ,但两者相比差异无统计学意义 (P >0 0 5 )。结论　西安市食管癌 p5 3基因第 5外显子的突变位点相对集中 ,林州市突变位点比较分散 ,可能与该地区多种危险因素的暴露有关。     

细胞色素P4501A1基因多态性与食管癌易感性关系的Meta分析

目的 探讨细胞色素P4501A1(CYP1A1)MspI和Ile/Val位点基因多态性与食管癌发生的关系.方法 采用Meta分析方法,对国内外1997-2008年采用病例对照方法研究CYP1A1MspI和Ile/Val基因多态性与食管癌发生关系的16篇(MspI 8篇,Ile/Val 14篇)文献,采用显性模型(即突变基因型与野生型比较)进行综合定量分析,然后按病理分型(鳞癌/腺癌)分亚组进行分析.结果 综合分析CYP1A1 MspI突变基因型(TC+CC)与食管癌发生无统计学关联(OR=1.17,95%CI:0.82～1.66),亚组分析亦未发现CYP1A1 MspI突变基因型与食管鳞癌(OR=1.17,95%CI:0.82～1.69)和食管腺癌(OR=1.39,95%CI:0.67～2.09)的统计学关联;携带CYP1A1突变基因型(Ile/Val+Val/Val)的个体发生食管癌的危险性是野生型的1.39倍(OR=1.39,95%CI:1.07～1.80);亚组分析显示突变基因型与食管鳞癌发生的易感性相关但与食管腺癌无关联,OR值分别为1.43(95%CI:1.07～1.91)和1.20(95%CI:0.62～2.30).结论 CYP1A1 Ile/Val位点突变基因型可增加食管鳞癌发生的危险性,CYP1A1 MspI位点基因多态性与食管癌无关联.     

DNA切除修复基因XPD751位点多态性与食管癌发病风险的Meta分析

目的 探讨DNA切除修复基因XPD751位点多态性与食管癌的发病风险关系.方法 检索中外数据库,获得有关XPD751位点多态性与食管癌发病风险的病例对照研究资料进行Meta分析,并按组织学类型进行分层分析,得到合并OR值(95%CI).结果 共纳入文献11篇,研究12项,累计食管癌病例2558例,对照5122例,与野生基因型Lys/Lys相比,Lys/Gln、Gln/Gln和(Lys/Gln+Gln/Gln)合并的OR值(95%CI)分别为1.19(1.05,1.34)、1.22(0.86,1.74)、1.20(1.01,1.42).分层分析显示,累计食管鳞癌病例1417例,对照2312例,携带Lys/Gln、(Lys/Gln+Gln/Gln)的个体患食管鳞癌的风险分别是Lys/Lys的1.22倍(95%CI:1.02,1.46)、1.24倍(95%C1:1.01,1.47);累计食管腺癌病例935例,对照2604例,未发现XPD751位点多态性与食管腺癌发病风险的统计学相关性.结论 XPD751位点杂合基因型Lys/Gln和(Lys/Gln+Gln/Gln)是食管癌发病的危险因素.XPD751位点杂合基因型Lys/Gln和(Lys/Gln+Gin/Gin)与食管鳞痛的发病风险相关,未发现XPD751位点多态性与食管腺癌的发病风险有关.     

甘肃省近30年间食管癌流行病学分析

[目的]探讨甘肃省近30年间经内镜检出食管癌的临床流行病特点.[方法]选择甘肃省163所医院30年间胃镜检查并经病理确诊的食管癌患者的病历资料,对其主要的内镜下改变、临床及组织学特点进行回顾性分析.[结果]30年来甘肃省食管癌总检出率为1.63%,食管癌高发于50～69岁,男性多见,以鳞癌为主(93.47%),好发于食管中段(54.78%);检出率武威市最高(5.03%).[结论]甘肃省食管癌以鳞癌为主,腺癌无明显上升趋势.食管腺癌好发于食管下段,而鳞癌多发于食管中上段.检出率以武威地区最高,在当地开展食管癌早期防治工作意义重大.     

河南安阳地区p53基因第72密码子多态性与HPV相关食管癌的研究

目的探讨河南安阳地区p53基因第72密码子多态性与人乳头瘤病毒(HPV)相关食管癌的关系。方法　收集安阳肿瘤医院食管癌病例110例,用PCR方法检测HPV, PCR-RFLP方法分析p53基因第72密码子多态性,病例病例对比研究方法分析在食管癌病例中HPV感染与p53基因第72密码子多态性的关系。结果　PCR检测结果表明,河南安阳地区食管癌组织中HPV检出率为59.1%;HPV阳性者中,Arg/Arg基因型的频率是60.0%,HPV阴性者中仅为17.8%,两者有统计学显著性(P<0.05)。结论　p53基因第72密码子多态性可能是安阳地区HPV相关食管癌的易感因素之一,携带p53 Arg/Arg基因型的个体更容易发生HPV相关的食管癌。     

p57~(kip2)和PCNA蛋白在西宁地区食管鳞癌中的表达

目的分析p57kip2和PCNA蛋白在西宁地区食管鳞癌组织中的表达,探讨其在食管鳞癌发生发展中的意义。方法选取60例食管鳞癌及其相对应的31例癌旁正常组织标本,应用免疫组化方法检测p57kip2和PCNA蛋白,并结合临床病理特点分析。结果p57kip2在食管鳞癌中的表达率为28.33%,低于癌旁正常组织的表达率(51.61%),并与食管鳞癌的分化程度、浸润深度有关,差异有统计学意义(P<0.05)。PCNA在食管鳞癌中的表达率为81.67%,高于癌旁正常组织的表达率(61.29%),与食管鳞癌的分化程度、浸润深度、淋巴结转移有关,差异有统计学意义(P<0.05)。p57KIP2与PCNA蛋白的表达呈负相关(rs=-0.611,P<0.01)。结论食管鳞癌组织中p57kip2低表达与PCNA的高表达共同参与食管癌的发生、发展。联合检测可作为预测食管鳞癌恶性程度和预后的重要指标。     

中国食管癌患者营养风险发生率的Meta分析

目的 系统评价我国食管癌患者营养风险发生率。方法 在PubMed、EMbase、Web of Science、CBM、CNKI、WanFang Data和VIP数据库中全面检索2020年2月8日前有关中国食管癌患者营养风险发生率的文章,并进行Meta分析。结果 共纳入28篇研究,含食管癌患者4 564名。中国食管癌患者总营养风险发生率为52%（95%%CI:0.44～0.60）。亚组分析结果显示:男性患者发生率为52%（95%CI:0.40～0.66）,女性患者发生率为53%（95%CI:0.41～0.64）;60岁以下及以上患者发生率分别为45%（95%CI:0.22～0.68）、57%（95%CI:0.42～0.72）;经手术或放化疗前及手术或放化疗后患者发生率分别为47%（95%CI:0.27～0.68）、57%（95%CI:0.26～0.89）;南北地区患者发生率分别为53%（95%CI:0.43～0.64）、49%（95%CI:0.39～0.59）。结论 我国食管癌患者营养风险发生率较高,且不同人群的营养风险发生率存在差异,因此,临床应给予高度重视。     

食管癌组织3p位点微卫星DNA序列不稳定性及3p24EAβMD位点杂合缺失的研究

[目的]探讨微卫星DNA序列不稳定性(MSI)表达水平及3p24位点杂合缺失与食管癌发生的关系.[方法]应用聚合酶链反应(PCR)和变性聚丙烯酰胺凝胶电泳技术,对35例人食管癌中MSI表达情况进行研究;同时利用PCR-RFLP法检测其3p24位点杂合缺失情况,并对该片段进行克隆.[结果]食管癌MSI多发生在3p位点,在35例食管癌患者中共检出8例杂合缺失.[结论]食管癌在3p染色体位点存在微卫星不稳定现象,3p24突变可能与食管癌的发生有一定相关性.MSI和3p24位点杂合缺失也许可作为临床筛查恶性肿瘤高危人群的分子手段,具有潜在的应用前景.     

早期食管癌的诊断

我国是食管鳞癌的高发地区 ,其病死率为 15 /10万左右 ,居全国恶性肿瘤死亡的前五位[1] 。所谓早期食管癌是指病灶浸润深度较为浅表 ,尚未出现区域淋巴结或远处脏器转移的病变 ,亦即UICC分期[2 ] 为Tis～T1N0 M0 的原位癌或I期食管癌 (见表1)。目前 ,手术切除仍然是治疗食管癌的主要手段 ,与大多数其他恶性肿瘤一样 ,食管癌的治疗效果与就诊时肿瘤的进展程度关系最为密切 ,虽然早期肿瘤可以通过手术获得根治 ,对进展期肿瘤的治疗效果仍然很不理想。国外报道[3] Ⅰ～Ⅳ期食管癌患者的总体 5年生存率分别为 5 0 %、31%、2 0 %和4 % ;国内…     

高危型HPV感染和p53基因多态性与食管癌关系的研究

[目的]阐明人乳头瘤病毒(HPV)感染和p53基因72密码子多态性与食管癌关系的研究,探讨两者在食管癌患者中发生的作用及其相互关系。[方法]收集安阳肿瘤医院食管癌病例110例、安阳对照20例与郑州对照25例,用PCR方法检测HPV,用PCR-RFLP方法分析p53基因第72密码子多态性,用病例对照方法分析HPV感染和p53基因72密码子多态性与食管癌的关系。[结果]PCR检测结果,安阳食管癌病例组织中HPV检出率(49.1%)高于安阳对照(15.0%)和郑州对照(16.0%,P<0.05);食管癌组Arg/Arg基因型频率(42.7%)高于郑州低发区对照(20.0%,P<0.05);HPV16阳性者中,Arg/Arg基因型的频率为55.6%,阴性者仅30.4%(P<0.05)。[结论]高危型HPV16感染可能是食管癌高发区的危险因素,Arg/Arg基因型可能是安阳地区食管癌的易感基因型,携带p53Arg/Arg基因型的个体更容易发生HPV相关的食管癌。     

Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors

Data from a population-based case-control study were used to evaluate the relation between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and low income contribute to the higher incidence among Black men than among White men in the United States. A total of 347 male cases (119 White, 228 Black) and 1,354 male controls (743 White, 611 Black) were selected from three US geographic areas (Atlanta, Georgia, Detroit, Michigan, and New Jersey). Cases were residents of the study areas aged 30-79 years who had been diagnosed with histologically confirmed esophageal cancer between 1986 and 1989. The adjusted odds ratios for subjects with annual incomes less than $10,000 versus incomes of $25,000 or more were 4.3 (95% confidence interval: 2.1, 8.7) for Whites and 8.0 (95% confidence interval: 4.3, 15.0) for Blacks. The combination of all four major risk factors-low income, moderate/heavy alcohol intake, tobacco use, and infrequent consumption of raw fruits and vegetables-accounted for almost all of the squamous cell esophageal cancers in Whites (98%) and Blacks (99%) and for 99% of the excess incidence among Black men. Thus, lifestyle modifications, especially a lowered intake of alcoholic beverages, would markedly decrease the incidence of squamous cell esophageal cancer in both racial groups and would narrow the racial disparity in risk. Further studies on the determinants of social class may help to identify a new set of exposures for this tumor that are amenable to intervention.     

The first molecular analysis of a Hungarian HNPCC family: a novel MSH2 germline mutation

BACKGROUND: Hereditary nonpolyposis colorectal cancer is an inherited disease characterized by onset at an early age, an excess of synchronous and metachronous large bowel tumors and a variety of extracolorectal malignancies. Basal and squamous cell carcinomas of the skin are not customarily included in the tumor spectrum of the syndrome. The disease is caused by a germline mutation in one of the DNA mismatch repair genes, most commonly MSH2 or MLH1, and typically presents with microsatellite instability and frequent loss of mismatch repair protein expression in the tumor tissue. PATIENT: The case of a 62-year old woman who had a history of colon cancer at the age of 46 years, endometrial cancer at the age of 56 years, baso-squamous, and squamous cell cancer of the face at the ages of 53, 54, 62 and 58 years, respectively, and rectal cancer at 60 is reported. Her family fulfills the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer. The baso-squamous cell, the squamous cell, the endometrial and the rectal cancers were assessed for the microsatellite instability status and the expression of the MSH2 and MLH1 mismatch repair proteins, and the p53 tumor suppressor protein by immunohistochemistry. Mutational screening using an automated capillary DNA sequencer was performed by the direct genomic sequencing of 17 fragments of the MSH2 gene, which covers promoter, all exons and flanking intronic regions. RESULTS: All cancers displayed microsatellite instability and were positive for the p53 protein. The immunohistochemical staining in the baso-squamous cell, the squamous cell, the rectal and endometrial cancers were negative for MSH2 and positive for MLH1 proteins. DNA sequencing analysis revealed a mutation c.2292G > A in exon 14 of the MSH2 gene, which is altering the 764. amino acid, the tryptophan to STOP codon (p.W764X). Thus the MSH2 protein is presumably truncated by 171 aminoacids. CONCLUSION: To the best of authors' knowledge, this is the first molecular characterization of a Hungarian hereditary nonpolyposis colorectal cancer family. According to the Human Mutation Database and International Collaborative Group of HNPCC Database, this mutation is novel, has not been reported previously. Cutaneous baso-squamous and squamous cell cancers may present as part of the HNPCC phenotype. Detection of the loss of mismatch repair protein expression and mismatch repair gene mutation mapping, represents a significant improvement of the diagnosis of this syndrome in Hungary. These examinations identify the mutation carriers who are at an increased risk of developing cancers.     

The excess incidence of squamous cell esophageal cancer among us black men. Role of social class and other risk factors

PURPOSE: To investigate the relationship between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and social class contribute to the five-fold higher incidence among black than white men in the United States.METHODS: Interviews were conducted with 347 incident cases of squamous cell esophageal cancer (119 white males and 228 black males) and 1354 population-based controls (743 white males and 611 black males) from Atlanta, Detroit, and New Jersey. Risks were estimated using unconditional logistic regression controlling for potential confounders.RESULTS: Elevated risks of squamous cell esophageal cancer were associated with indicators of low social class, especially low annual income. The adjusted odds ratios (ORs) for subjects with incomes < $10,000 versus incomes of $25,000 or more were 4.3 (95% CI = 2.1-8.7) for whites and 8.0 (95% CI = 4.3-15.0) for blacks. The combination of all four major risk factors: annual income less than $25,000, moderate/heavy use of alcohol, use of tobacco for six months or longer, and consumption of less than 2.5 servings of raw fruits and vegetables per day accounted for almost all of the squamous cell esophageal cancers in whites (98%) and blacks (99%), and for 99% of the excess incidence among black men.CONCLUSIONS: Lifestyle modifications, especially a lower intake of alcoholic beverages, would markedly decrease the incidence of this cancer in both races and narrow the racial disparity in risk. Further studies into the determinants of social class may help identify a new set of exposures for this tumor that are amendable to intervention.     

食管癌与p53突变和人乳头状肉瘤病毒感染

目的探讨p53基因突变与人乳头状肉瘤病毒16（HPV16）感染在食管癌发病中的作用及相互关系。方法应用病例-病例研究方法进行分析，采用聚合酶链反应（PCR）、单链构像多态性（SSCP）、测序等分子生物学技术对110例食管癌组织标本中p53基因的突变与HPV16感染进行了检测。结果110例食管癌组织标本p53基因突变率为49．1％，其中外显exon5—6，exon7，exon8—9的突变率分别为19．1％，27．3％，17．2％。食管癌组织HPV16的检出率为49．1％。吸烟患者p53基因突变率（61．4％）明显高于非吸烟患者p53基因突变率（48．2％），差异有统计学意义；淋巴结转移患者p53基因突变率（65．2％）明显高于无淋巴结转移患者p53基因突变率（37．5％）；HPV16阳性者中，p53突变率是40．7％，HPV16阴性者仅为57．1％，两者差异无统计学意义。结论HPV16感染可能是食管癌高发区的危险因素；p53基因突变与吸烟、淋巴结转移有明显相关性；HPV16感染和p53基因突变可能是2个独立的事件。     

Effect of learning about the human genome on the development of pathology

On the basis of data of the Human Genome Project, it was embraced the newest information about the gene content of the human genome, the disease genes, the parasitic DNA, the single nucleotide polymorphisms, the repeat sequences, the cytoskeletons, the regulation of cell proliferation, and their medical consequences. The applicability of the acquaintance with the human genome in pathology is presented with a few examples of our own. The significance of the single nucleotide polymorphisms in susceptibility to, or protection from, a host of disease is illustrated by the example of the allele variation of Apo-E gene. The copy number of the N-myc gene in neuroblastomas and HER2/neu gene in breast carcinomas was determined with quantitative PCR techniques. The monoclonally increased abnormal p53 protein expression was found in small cell lung cancer (in 90% frequency), in oro-pharyngeal carcinomas (82%), in esophageal squamous cell carcinomas (59%) in stomach cancer (33%), in colon carcinomas (27%) and in soft tissue sarcomas (13%). These data advert to the fact that the mutation of the p53 gene is much more frequent in those tumors in which the basic tissue is directly exposed to with the environmental carcinogens. It is now known, that near the repetitive sequences, gene rearrangement can more easily be evolve. Finally, we have determined the conditions of the accomplishment of the molecular pathological diagnosis: (1) It is applicable, when the classic morphology does not eventuate a conclusive result. (2) Well known and validated gene alterations are admissible to diagnostic purpose. (3) Only standard methods are applicable along with positive and negative controls. (4) The result has to correlate with the morphological picture, the immunohistochemical profile and the clinical data. (5) It is necessary to be able to appropriately interpret the molecular biological result, which is then incorporated in the pathological report. (6) The ethical, legal and social consequences must be considered.     

吸烟、饮酒与食管癌p53基因改变的Meta分析

目的 探讨吸烟、饮酒与食管癌p53基因改变之间的关系。方法 应用Meta分析对有关研究吸烟、饮酒与食管癌p53基因改变的文献进行综合评价。结果 纳入Meta分析的14篇研究吸烟的文献中,吸烟与P53蛋白高表达、p53基因改变(P53蛋白高表达 p53基因突变)的合并OR值分别为1.99(95％CI:1.30～3.06)、1.64(95％CI:1.13～2.37)(P<0.05),吸烟与p53基因突变的合并OR值为1.11(95％CI:0.47～2.76)(P>0.05)。11篇研究饮酒的文献中,饮酒与P53蛋白高表达、p53基因突变和p53基因改变的合并OR值分别为1.30(95％CI:0.83～2.04)、1.13(95％CI:0.67～1.90)和1.22(95％CI:0.87～1.72),合并OR值无统计学意义(P>0.05)。结论 吸烟与p53基因改变有显著联系,饮酒与p53基因改变未见显著联系。     

林州食管癌发病因素病例对照研究

目的 探讨林州居民食管癌发病的相关因素及其特征。方法 在全市１９９５、１９９６两年新发生的食管癌病人中,选取３５２例现症病人;另选取同性别、同年龄（上下不超过３岁）的邻居为对照,进行１：１配对,采用统一调查表,进行回顾性入户问卷调查,资料编码量化后录入微机,应用ＳＡＳ软件,计算单因素和多因素的比值比,对相对危险进行估计。结果 显示农民家庭经济条件差,住地周围环境污染,室内油烟污染,体质指数低,常吃     

p53基因突变和蛋白表达改变在食管癌预后作用中的Meta分析

目的 探讨p53基因突变及P53蛋白表达改变对食管癌预后的影响。方法 应用Meta分析方法Dersimonian-Laird模型对有关p53改变与食管癌预后的文献进行定量综合分析,共人选27篇文献,累计病例2174例,p53阳性1150例,阳性率52.9％。结果 对入选27篇文献一致性检验,q值为59.88,P<0.005,文献具有异质性,合并相对危险比为2.07,95％可信区间为1.58～2.70。结论 p53改变可能是食管癌患者不良预后的一个生物标志物,有利于食管癌的治疗决策。     

浊漳河水及改水对林州市居民年龄别食管癌发病率的影响

目的探讨浊漳河水及改水对林州市居民食管癌性别、年龄别发病率的影响。方法对林州市居民食管癌性别、年龄别发病率时间变化与浊漳河水(红旗渠水)水量变化关系进行相关分析。结果1959年—2003年间,林州市食管癌发病率、死亡率随浊漳河水、红旗渠水的水量时多、时少而上升和下降。1959年—1963年红旗渠通水前食管癌的性别、年龄别发病率相对偏低。红旗渠通水6年后,即1969年—1970年食管癌发病率、死亡率达到历史高峰期,随后,当红旗渠水量减少和恢复时,食管癌发病率、死亡率随之显著下降和显著上升。1995年全县85%的居民改用地下水后,食管癌发病率、死亡率稳定在较低水平。结论林州市居民食管癌发病率时间变化与浊漳河水量变化相一致、并有时间先后关系,先浊漳河水量变化,5-10年发病率随之变化。预防措施应加强"氮循环"病因学说的宣传教育,要特别预防浊漳河水源的工农业污染,净化红旗渠水后再灌溉土地,同时加强饮用水管理和检测,改水、改厕、改善环境卫生、保护水源是预防食管癌的关键措施。