胰腺癌的遗传易感性

胰腺癌是一种致死性疾病，即使千亍胰腺癌的彻底根治术，其5年存活率仍不足5％。胰腺癌的发病及转移与其他肿瘤一样，是由遗传性和获得性肿瘤生成基因累积所致，而单纯南遗传因素引起的肿瘤对研究肿瘤的发牛机制具有独特意义。近年来，基因遗传因素与肿瘤发生的关系逐渐引起肿瘤研究人员的重视，重新调整肿瘤预防策略。     

细胞因子基因多态性与结核遗传易感性关系的研究进展

结核病是发展中国家常见的疾病,病死率高.众多研究表明,全球约有1/3的人群感染过结核分枝杆菌,但仅有5%～10%的感染个体最终发展为临床结核,说明结核病的发生发展存在着遗传易感性.细胞因子是结核病免疫的重要组成部分,细胞因子的基因多态性影响着细胞因子的水平,而且与疾病的结局存在相关性.本文就结核病中重要的细胞因子的基因多态性与结核遗传易感性的关系作一综述.     

基因的多态性与食管癌的易感性

食管癌的癌变机制仍不清楚，值得关注的是遗传因素在食管癌发生中起的作用，本主要介绍参与致癌物代谢的相关基因(CYP、ADH、GST、ALDH、NAT)、与DNA稳定性有关的基因(MTHFR、XRCCl、HOGGl)以及某些抑癌基因(P53)，探讨它们的多态性与食管癌的易感性关系。     

TSLP基因多态性与支气管哮喘遗传易感性的关系

支气管哮喘（简称哮喘）是多基因参与的具有遗传易感性的慢性气道变应性炎症。胸腺基质淋巴细胞生成素（TSLP）是一种由上皮细胞产生的白介素7样细胞因子,与靶细胞TSLP受体相互作用,激活骨髓源性树突状细胞,并诱导一种特殊类型的炎症性Th2免疫应答,参与哮喘的发生和发展。TSLP还可通过调节核因子κB,参与哮喘的发病过程。多数家系聚集、孪生和大的遗传队列研究均证明,哮喘存在遗传易感性。靶向TSLP有望为今后哮喘免疫治疗带来新的前景。     

基因多态性与胃癌遗传易感性的关系

胃癌的发生是一个多因素、多步骤的复杂过程,环境因素与遗传因素的相互作用决定了这一过程的发展和结局.幽门螺杆菌（Hp）感染及饮食因素是经大量研究确认的胃癌高危因素.胃癌的遗传易感性分为强遗传易感性和弱遗传易感性.     

HLA-DQB1基因多态性与重症肌无力遗传易感性的关系

2001～2003年，我们运用PCR-SSP方法对中国北方地区49例重症肌无力(MG)与HLA-DQB1的相关性进行分析，以期进一步探讨MG免疫学异常的机制，并为寻找MG的易感基因提供线索。     

X线交错互补修复基因1多态性与前列腺癌的遗传易感性

选择华东地区207例前列腺癌（PCa）患者为作为病例组,235例非肿瘤、非前列腺疾病的男性患者作为对照组。用PCR-RFLP方法分析两组X线交错互补修复基因1（XRCC1）Arg194Trp和Arg280His两个位点的多态性,比较不同基因型与PCa易感性的关系。结果显示,XRCC1第194密码子携带194Trp等位基因的个体（Arg/Trp＋Trp/Trp）患PCa的风险较Arg/Arg基因型的个体降低38%（校正OR=0.62,95%CI为0.410.93）;在≤70岁及不吸烟两组人群中,携带194Trp等位基因的个体PCa发病风险比Arg/Arg基因型的个体分别降低45%（OR=0.55,95%CI为0.30-1.00）和52%（校正OR=0.48,95%CI为0.24-0.95）。认为XRCC1 Arg194Trp位点多态性可能对PCa遗传易感性产生影响,并与吸烟在PCa的发病中有一定的协同作用。     

N-乙酰基转移酶基因多态性与肝癌易感性的关系

目的探讨N-乙酰基转移酶(NAT2)基因多态性与肝癌易感性的关系。方法应用自动实时荧光Light-Cycler技术,分析78例肝癌患者和112例健康志愿者NAT24个位点的基因多态性,比较肝癌患者与对照组间频率差异。结果 肝癌吸烟组NAT2慢乙酰化基因型频率(37.5％)与对照吸烟组(17.9％)比较差异有显著性(X2=4.67,P<0.05),并使患肝癌的危险度提高了2.76倍;肝癌非吸烟组NAT2慢乙酰化基因型频率(26.3％)与对照非吸烟组(16.1％)比较差异无显著性(X2=1.47,P>0.05)。结论携带NAT2慢乙酰化基因型的吸烟者可能是肝癌的高危人群。     

MMP-2基因多态性与青海世居汉族女性乳腺癌易感性的关系

目的 探讨青海高原世居汉族人群女性乳腺癌易感性与基质金属蛋白酶2（MMP-2）基因启动子附近1306C/T、735C/T位点基因多态性的关系.方法 采用病例对照研究方法,选取30例青海高原世居汉族女性乳腺癌患者（癌症组）和30例年龄、性别相匹配的乳腺良性病变患者（对照组）;应用聚合酶链反应—限制性片段多态性（PCR-RFLPs）法检测MMP-2基因1306C/T、735C/T位点多态性,运用统计学方法对其基因频率进行分析.结果 MMP-2基因1306C/T位点CC、CT、TT基因型频率在对照组中分别是66.7％、23.3％、10.0％,在癌症组中分别是73.3％、20.0％、6.7％,P均＞0.05;C、T基因频率在对照组中是78.3％、21.7％,在癌症组中是83.3％、16.7％,P均＞0.05.MMP-2基因735C/T位点CC、CT、TT基因型频率在对照组中分别是76.7％、16.6％、6.7％,在癌症组中分别是53.3％、40.0％、6.7％,两组CC、CT基因型频率比较,P均＜0.05;C、T基因频率在对照组中是85.0％、15.0％,在癌症组中是73.3％、26.7％,P均＞0.05.结论 MMP-2基因启动子附近1306C/T基因多态性可能与青海高原世居汉族女性乳腺癌易感性无关,携带MMP-2基因735C/T位点CT基因型的女性罹患乳腺癌的风险较高.     

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。     

基质金属蛋白酶-2和-9在食管鳞状细胞癌中的过表达

目的 探讨人食管鳞癌组织中基质金属蛋白酶(MMP)-2、-9的表达及其临床意义.方法 采用免疫组织化学法,检测57例食管鳞癌及10例食管正常黏膜石蜡标本中MMP-2、-9蛋白的表达情况.结果 食管鳞癌组织中MMP-2及MMP-9阳性表达率(40.3%,61.4%)显著高于正常组织(0.0%,10.0%)(P＜0.05).食管鳞癌组织中MMP-2及MMP-9阳性表达与淋巴结转移和癌组织浸润深度有显著相关性(P＜0.05),而与患者的性别、年龄和组织分化程度无显著相关性(P＞0.05).结论 MMP-2和MMP-9在食管癌中显著高表达,与食管癌的转移及侵袭有关,其异常表达可能共同参与食管癌的发生、发展过程,检测MMP-2、-9可作为食管癌病理学特点的参考指标.     

NOS1基因多态性与湖北汉族人变应性哮喘易感性的关系

目的　研究一氧化氮合成酶结构式基因 (NOS1)第 2 9外显子翻译终止位点下游 2 76 bp处 C/ T(C5 2 6 6 T)位点多态性与湖北汉族人变应性哮喘易感性及血浆 Ig E水平的关系。方法　用聚合酶链反应和限制片段长度多态性 (PCR- RFL P)方法对湖北汉族 134例变应性哮喘患者 (哮喘组 )及 90例无血缘关系的汉族健康人(对照组 )进行 NOS1基因 C5 2 6 6 T位点多态性分析 ,用免疫发光法测定血浆总 Ig E水平。结果　哮喘组 NOS1基因 C5 2 6 6 T位点 TT基因型频率与对照组相比差异显著 (P=0 .0 0 9) ,T等位基因频率与对照组相比无显著性差异 (P>0 .0 5 )。哮喘组 TT基因型者血浆总 Ig E显著高于 CC和 CT基因型者 (P<0 .0 5 )。结论　 NOS1基因C5 2 6 6 T位点 TT基因型与湖北汉族人哮喘易感性和高血浆总 Ig E水平均相关。     

GSTM1基因多态性与中国汉族人群肺癌易感性的Meta分析

目的 探索谷胱甘肽硫转移酶M1(GSTM1)基因多态性与中国汉族人群肺癌发生的相关性.方法 检索2011年8月之前GSTM1基因多态性与肺癌相关性的相关文献,根据纳入、排除标准选择符合要求的文献,整理GSTM1功能型基因型、缺失型基因型频数或频率,采用Mantel-Haenszel固定效应模型分析合并OR值,并用漏斗图和Egger线性回归分析评估文献的发表偏倚.结果 GSTM1(-)基因型携带者发生肺癌的风险是GSTM1(+)基因型携带者的1.64倍(95％CI:1.43～1.87),有统计学意义(Z=7.19,P＜0.01);发表偏倚的漏斗图对称,Egger线性回归分析回归截距为-0.422(95％CI:-3.011～2.167),无发表偏倚(P=0.734).结论 GSTM1基因是肺癌发生的易感基因,其中GSTM1缺失型基因型是中国汉族人群发生肺癌的风险因子.     

卵磷脂胆固醇酰基转移酶基因608C/T和511C/T多态性与湖南地区汉族人卒中的关系

目的 探讨卵磷脂胆固醇酰基转移酶(1ecithin cholesterol acyltransferase,LCAT)基因608C/T和511C/T多态性与中国湖南地区汉族人群卒中发病的关系.方法 选择150例脑梗死、150例脑出血患者以及122名年龄和性别相匹配的对照者,应用聚合酶链反应、单链构象多态性技术和限制性片...     

Establishment of risk model for pancreatic cancer in Chinese Han population

AIM: To investigate risk factors for pancreatic cancer and establish a risk model for Han population. METHODS: This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio (ORs), 95% confidence intervals (Cls) andβvalue, which were further used to establish the risk model. RESULTS: According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR 1.98; 95% CI 1.11-3.49, P= 0.017). More importantly, heavy smokers in men had increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P=0.012) than women. Heavy alcohol drinkers (>20 cup-years) had increased risk for pancreatic cancer (OR 3.68; 95%CI 1.60-8.44). Daily diet with high meat intake was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% (P= 0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its importance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer. CONCLUSION: Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Han population has been established with an 88.9% sensitivity and a 97.6% specificity.     

A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene

AIM: To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer. METHODS: Polymerase chain reaction and direct sequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis. Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects. RESULTS: A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C>T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT>TGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects. CONCLUSION: Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.     

CCL5基因rs2280788多态性与肺结核易感性关系的meta分析

目的 探讨CCL5基因rs2280788多态性与肺结核病易感性关系.方法 计算机检索数据库,收集有关CCL5基因rs2280788多态性与肺结核病易感性关系病例对照研究,提取纳入文献的相关数据进行meta分析,以病例组与对照组CCL5基因rs2280788位点各种基因模型的比值比(OR)为效应指标,漏斗图检测发表偏倚.结果 共6篇研究符合纳入标准,累计病例数1364例,对照组1581例.meta分析表明CCL5基因rs2280788多态性与肺结核病易感性无明显关联性.纯合子比较模型(GG vs CC):OR=1.28,95％ CI:0.47～3.47,P=0.62;杂合子比较模型(CG vs CC):OR =1.19,95％CI:0.82～1.72,P=0.36;显性遗传模型(CG+GG vs CC):OR =1.27,95％CI:0.81～1.99,P=0.29;隐性遗传模型(GG vs CC+GC):OR =1.21,95％CI:0.49～2.98,P=0.68.结论 CCL5基因rs2280788多态性与肺结核病易感性无明显关联性.     

E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population

AIM: To test the hypothesis that E-cadherin gene (CDH1) C-160A promoter variant genotype is associated with an increased risk for developing gastric cancer. METHODS: In this population-based case-control study of gastric cancer in Jiangsu Province, China, we performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the C-160A polymorphism of CDH1 promoter in 206 non-cardia gastric cancer patients and 261 age- and sex-matched but unrelated cancer-free controls. RESULTS: The frequencies of genotypes CC, CA and AA were 57.8%, 36.4% and 5.8% in gasfric cancer cases, respectively, and 58.2%, 34.9% and 6.9% in controls respectively. The distributions of CDH1 genotypes were not significantly different between gastric cancer cases and controls (P=0.87 for genotype frequency and P=0.92 for allele frequency). Compared with the CC genotype, the CA and AA genotypes were not associated with an increased risk for non-cardia gastric cancer (adjusted odds ratios (OR)=1.15, and 95% confidence interval (95% CI)=0.78-1.72 for CA genotype, and OR = 0.90 and 95% CI = 0.42-2.01 for AA genotype). CONCLUSION: E-cadherin gene C-160A promoter polymorphism may not play a major role in the etiology of non-cardia gastric cancer in Chinese population.     

中国藏族PSCA基因rs2294008多态性与胃癌遗传易感性的关系

目的:研究前列腺干细胞抗原基因(prostatestem cell antigen gene,PSCA)rs2294008位点多态性与中国藏族胃癌患者遗传易感性的关系.方法:收集185例藏族胃癌患者与200例健康人群的外周血样本,提取基因组DNA,采用dHPLC方法进行PSCA基因rs2294008位点分型.结果:PSCA基因rs2294008位点3种基因型C C、C T、T T在胃癌病例组中频率分别为:40.00%、48.65%和11.35%,而在对照组中分别为54.00%、39.50%和6.50%.与CC型比较,携带CT,TT型基因型者胃癌发生的危险性增加,OR值分别为1.66(95%CI 1.09-2.54)和2.36(95%CI 1.11-5.00).结论:PSCA基因rs2294008位点CT,TT基因型增加中国藏族人群的胃癌易感性.