胃癌患者白细胞介素-1B基因多态性及序列测定的初步研究

目的：检查国人胃癌中IL-1B基因启动子区域-31C／T多态性，初步分析其基因型与胃癌的相关性。方法：应用聚合酶链反应一限制性片段长度多态性(PCR—RFLP)分析技术，对收集的50例胃癌癌旁正常组织和50例正常健康人外周血标本，提取DNA进行PCR扩增，然后用Alu Ⅰ限制性内切酶对PCR产物进行消化，经琼脂糖凝胶电泳对IL-1B基因多态性进行分析，并对C／C和T／T进行序列测定。结果：IL-1B基因-31C等位基因频率在正常人和胃癌患者中分剐为75％和53％，-31T等位基因频率则分别为25％和47％。正常人和胃癌患者中3种基因型频率分别为-31C／-31C：56％(28／50)和30％(15／50)；-31C／-31T：38％(19／50)和46％(2．3／50)；-31T／-31T：6％(3／50)和24％(12／50)。携带-31T等位基因增加罹患胃癌的危险性，-31C／-31T杂合子和-31T／-31T纯合子分别增加2．3和7．5倍。并经DNA序列测定证实在IL-1B基因启动子区域有-TATA框多态，即-31碱基发生C—T转换。结论：IL-1B基因启动子区域-31C／T多态性与国人胃癌易患性相关。     

IL-1B基因多态性与胃癌易感相关性研究

目的:探讨河南地区汉族人白细胞介素(IL)-1B基因多态性与胃癌的相关性以及是否与胃癌组织学分型相关联.方法: 采用聚合酶链反应-单链构象多态性技术(PCR-SSCP)和琼脂糖凝胶电泳(AGE)检测了220例对照和452例胃癌患者(肠型176例,弥散型137例,萎缩型139例)的IL-1B-511C/T基因位点.结果: IL-1B-511C等位基因频率在正常人群和胃癌组患者分别为0.82和0.76,IL-1B-511T 等位基因频率分别为0.18和0.24,两者差异有统计学意义.IL-1B-511T纯合子、携带者患肠型胃癌风险的OR分别为2.7(95% CI:1.5～4.9)和3.1(95% CI:1.5～6.5);T等位基因与肠型胃癌易感密切关联,与萎缩型胃癌易感差异无统计学意义,P＞0.05.结论: IL-1B-511C/T基因多态性与胃癌发生风险密切关联,T等位基因可能是肠型胃癌的易感标志.     

IL-1B基因多态性与胃癌易感相关性研究IL-1B基因多态性与胃癌易感相关性研究

目的：探讨河南地区汉族人白细胞介素（IL）-1B基因多态性与胃癌的相关性以及是否与胃癌组织学分型相关联.方法： 采用聚合酶链反应-单链构象多态性技术（PCR-SSCP）和琼脂糖凝胶电泳（AGE）检测了220例对照和452例胃癌患者（肠型176例,弥散型 137例,萎缩型139例）的IL-1B-511C/T基因位点.结果： IL-1B-511C等位基因频率在正常人群和胃癌组患者分别为0.82和0.76,IL-1B-511T 等位基因频率分别为0.18和0.24,两者差异有统计学意义.IL-1B-511T纯合子、携带者患肠型胃癌风险的OR分别为2.7（95% CI：1.5～4.9）和3.1（95% CI：1.5～6.5）;T等位基因与肠型胃癌易感密切关联,与萎缩型胃癌易感差异无统计学意义,P＞0.05.结论： IL-1B-511C/T基因多态性与胃癌发生风险密切关联,T等位基因可能是肠型胃癌的易感标志.     

胃癌发病风险与醌氧化还原酶基因多态性的关系

目的探讨醌氧化还原酶基因多态性与胃癌发病的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法分析了80例胃癌患者与80名健康成人NQO1的基因多态性。结果醌氧化还原酶基因cDNA609位T等位基因频率在胃癌组和对照组分别为55%和42.5%,两组比较差异有统计学意义,χ2=5.00,P=0.018。基因型分布在胃癌组和对照组之间差异有统计学意义,χ2=7.63,P=0.025。杂合型(T/C)和突变纯合子型(T/T)基因型携带者患胃癌的危险性分别是野生型纯合子(C/C)的2.84倍(95%CI1.2451~6.4780)与3.60倍(95%CI1.2970~9.9925)。结论NQO1cDNA609T等位基因可能是胃癌发生的危险性因素,与胃癌的发生有关。     

转化生长因子-β1基因多态性与结直肠癌关系的研究

目的:研究转化生长因子β1(TGF-β1)基因启动子多态性各等位基因及基因型在结直肠癌患者中的分布频率,初步分析基因型及血清水平与结直肠癌的相关性。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测120例结直肠癌患者和130例正常对照组TGF-β1的基因多态性,包括TGF-β1基因启动子-800G/A、-509C/T位点,同时采用酶联免疫吸附试验(ELISA)检测血清TGF-β1水平。结果:结直肠癌患者血清TGF-β1水平显著高于对照组(P<0.01)。TGF-β1基因-800G/A位点多态性在结直肠癌组和正常人群中的分布差异无显著性(P>0.05);而TGF-β1基因-509C/T多态性各等位基因及基因型频率在两组人群中的分布差异存在显著性(P<0.05),等位基因频率的相对风险分析发现,T等位基因携带者患结直肠癌的风险是C等位基因的1.580倍(OR=1.580,95%C I:1.109~2.251)。携带T等位基因的结直肠癌患者血清TGF-β1水平显著高于不携带者(54.77±12.65 ng/mLvs44.29±10.24 ng/mL,P<0.01)。结论:TGF-β1基因-509C/T多态性与结直肠癌的发病具有相关性,携带T等位基因的个体可能通过促进TGF-β1的高度表达进而增加了结直肠癌的发病风险。     

VEGF基因-460T/C单核苷酸多态性与河北地区汉族人群肺癌发病风险相关性分析

目的:研究血管内皮生长因子(VEGF)基因启动子区-460T/C单核苷酸多态性(SNP)与河北地区汉族人群肺癌发病风险的关系。方法:采用基于医院的病例-对照研究方法,采集200例肺癌患者和204名健康对照的静脉血,同时记录其病史和个人相关资料。以蛋白酶K消化-饱和氯化钠盐析法提取外周血白细胞DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和引物介导的限制性聚合酶链反应(PIRA-PCR)方法检测VEGF-460T/C多态性位点的基因型。结果:肺癌组VEGF-460C/T SNP C等位基因频率(27.5%)明显高于对照组(20.1%),两组比较差异有统计学意义,χ2=6.109,P=0.013。肺癌组与对照组的T/T、T/C+C/C基因型频率分别为52.2%、47.5%和63.2%、36.7%,差异有统计学意义,χ2=4.445,P=0.029。与T/T基因型相比,携带C等位基因(T/C+C/C)的基因型可显著增加肺癌的发病风险;与T/T基因型相比,携带C等位基因(T/C+C/C)的基因型可显著增加不吸烟人群的发病风险。与T/T基因型相比,携带C等位基因的基因型(T/C+C/C),明显增加肺鳞状细胞癌及小细胞癌发病风险。结论:VEGF-460T/C SNP可能与肺癌发病风险相关。     

Toll样受体2基因多态性与胃癌及EB病毒相关胃癌易感性的关系

目的:探讨Toll样受体2(TLR2) rs3804099和rs3804100基因多态性与胃癌和EB病毒相关胃癌(EBVaGC)易感性的关系。方法:选用185例EBV阴性胃癌(EBVnGC)组织、41例EBVaGC组织以及100位健康人群外周血标本作为研究对象,采用PCR结合限制性片段长度多态性(RFLP)技术检测TLR2 rs3804099与rs3804100的基因多态性。结果:TLR2 rs3804099基因型和等位基因频率在胃癌组与健康对照组间的差异均有统计学意义(χ²=5.617,P=0.018;χ²=6.467,P=0.011),胃癌组C等位基因频率及C等位基因携带者频率均明显高于健康对照组(χ²=6.467,P=0.011;χ²=4.444,P=0.035),且与野生TT型相比,CC基因型可增加胃癌的发病风险(OR=3.554, 95%CI=1.179~10.715)。TLR2 rs3804100位点的各基因型频率、C等位基因及C等位基因携带者的频率在胃癌组和健康对照组之间差异无统计学意义(P>0.05)。TLR2 rs3804099与rs3804100位点的各基因型频率、C等位基因频率及C等位基因携带者频率在EBVaGC和EBVnGC两组间的差异均无统计学意义(P>0.05)。结论:TLR2 rs3804099基因多态性可能与胃癌发病风险有关,C等位基因可能为胃癌的危险因子,携带C等位基因可能增加胃癌的发病风险。TLR2 rs3804099与rs3804100基因的多态性与EBVaGC的易感性无明显相关性。     

环氧化物水解酶Tyr113His多态性与中国北方人群食管鳞状细胞癌易感性的研究

目的 :研究微粒体环氧化物水解酶Tyr113His多态性与中国北方人群食管鳞状细胞癌 (esophagealsquamouscellcarcinoma ,ESCC)易感性的关系。方法 :采用限制性片段长度多态性聚合酶链反应 (polymerasechainreaction re strictionfragmentlengthpolymorphism ,PCR RFLP)方法分析 2 5 7例食管癌患者和 2 5 2名健康对照组人群mEHTyr113His基因型分布。结果 :Tyr和His等位基因频率在食管癌患者和健康对照组中分别为 44 2 %、5 5 8%和 44 0 %、5 6 0 %。等位基因分布在两组之间差异无统计学意义 ,χ2 =0 0 0 8,P =0 92 9;基因型分布在病例组与对照组之间差异也无统计学意义 ,χ2=2 116,P =0 3 47。相对于Tyr/Tyr基因型 ,His/His基因型或His/His与Tyr/His基因型相加均未增加ESCC的发病风险。它们的危险度分别为 1 0 76( 95 %可信区间 =0 85 0～ 1 3 61)和 0 75 6( 95 %可信区间 =0 493～ 1 15 7)。如按性别、年龄、吸烟状态及是否具有上消化道肿瘤家族史进行分类 ,His/His基因型或His/His与Tyr/His基因型相加也未对ESCC的发病风险造成明显影响。结论 :mEH的Tyr113His多态性不能作为筛查ESCC患病风险的独立因素。     

TLR3和TLR4基因多态性与EBV相关胃癌易感性的关系

目的 探讨TLR3c.1377和TLR4Asp299Gly基因多态性与EBV感染在EBV相关胃癌（EBVassociated gastric carcinoma, EBVaGC）发生中的相关性。方法 选用41例EBVaGC组织、62例EBV阴性胃癌（EBV-negative gastric carcinoma, EBVnGC）组织以及64例健康人群血标本作为研究对象,采用PCR结合限制性长度多态性分析（reaction-restriction fragment length polymorphism, RFLP)技术检测TLR3c.1377 和TLR4 Asp299Gly基因多态性,并对实验结果进行统计分析。结果 （1）胃癌组与对照组比较TLR3c.1377基因型频率差异有统计学意义（P=0.025）,胃癌组T等位基因频率明显高于对照组（45.6% vs. 29.7%,P=0.004),T等位基因携带者的患病风险明显高于非携带者(OR=2.435,P=0.008）;（2）EBVaGC、EBVnGC以及对照组间TLR3c.1377基因型、等位基因频率差异无统计学意义（P>0.05）。（3）EBVaGC组,EBVnGC组以及正常对照组所有个体TLR4 Asp299Gly基因型均为Asp/Asp纯合子（P>0.05）。结论 TLR3c.1377基因多态性与胃癌易感性有关,T等位基因为胃癌的危险因子,而C等位基因为一保护基因;TLR3c.1377基因多态性与EBVaGC易感性无明显相关。     

The contribution of molecular genetics to the understanding and management of cancer: potential future applications and implications for nurses

Cancer is an immense medical problem and as a cause of mortality it is second only to cardiovascular disease. Much of the current understanding of cancer is owed to epidemiologists who have discovered a number of causative factors implicated in its development. These causative factors can be divided into genetic, chemical, physical, viral, radiation, immune and hormonal factors. Further advances in understanding have been made over the past decade from contributions made by the field of molecular biology. From investigation and examination of the molecular processes involved in the development of cancer it is becoming increasingly clear that changes in the genetic material of the cell nuclei are the final common pathway to cancer, whatever the initial aetiology. This article will attempt to elucidate the contribution of molecular genetics to the understanding of the likely mechanisms of carcinogenesis, the management of cancer, potential future applications and directions and the implications for nurses arising from this relatively new and evolving field of knowledge.     

基质金属蛋白酶MMP-2和MMP-9在食管癌组织中的表达意义

目的 :探讨基质金属蛋白酶MMP 2和MMP 9在食管癌组织中的表达及其与食管癌浸润转移的关系。方法 :用免疫组化S P法检测 5 9例食管癌组织中MMP 2和MMP 9的表达。结果 :MMP 2和MMP 9阳性表达率在食管腺癌分别为 84 6 1%、76 92 % ,明显高于食管鳞癌 5 0 0 0 %、4 3 4 8% (P <0 0 5 ) ;淋巴结转移组分别为 93 33%、86 6 7% ,明显高于无淋巴结转移组 4 1 38%、37 93% (P <0 0 1)。结论 :MMP 2和MMP 9可能在食管癌侵袭及转移过程中发挥重要作用。     

宫颈癌染色体杂合性丢失及HPV感染状态的研究

目的 :研究宫颈癌组织染色体 3p和 10q位点的杂合性丢失 (LOH)与人乳头瘤病毒 (HPV)感染状态及临床病理参数之间的关系。方法 :选择 3p和 10q 6个微卫星位点 ,对 5 2例宫颈浸润癌、33例不典型增生和 12例正常宫颈进行LOH及HPV感染状态分析。结果 :浸润癌中LOH阳性的比例明显高于CIN组及正常宫颈组 ,P <0 0 1;3p的LOH阳性率明显高于 10q ,P <0 0 5 ;Ⅲ和Ⅳ期明显大于Ⅰ和Ⅱ期 ,P <0 0 5 ;LOH阳性率在 3p鳞癌高于腺癌 ,在 10q腺癌高于鳞癌 ,但与组织学类型无关。浸润癌中HPV感染阳性率明显高于CIN组及正常宫颈组 ,P <0 0 5 ;3p的LOH阳性率在HPV感染阳性组明显高于阴性组 ,P <0 0 5。结论 :宫颈癌染色体 3p和 10q的LOH高频区可能存在宫颈癌相关抑癌基因 ,HPV感染与 3p的LOH共同作用在宫颈癌发展过程中更有意义。     

Establishing a Cancer Genetics Programme in Asia - the Singapore Experience

Cancer genetics is now an established oncology subspecialty with the primary prevention role of identifying high-risk individuals through genetic information for enrolment into screening and preventive programmes. Integrated into major Western centres since the late 1990s, such a programme has been established in Singapore since 2001. Our programme has evaluated 367 index patients comprising mainly breast and colorectal cancer cases. Cancer patients were receptive to genetic counselling, but cost posed a major barrier to genetic testing. However, when the cost barrier was removed through government subsidy plans, more than half of high-risk patients still declined testing. The major barriers were reluctance to involve family members, perception that the information would not change management, and fears of negative feelings. Confirmed mutation carriers were compliant to screening and receptive to prophylactic surgery. Uptake of predictive testing among cancer-free family members has been low, possibly arising from the stigma associated with cancer in our Asian culture. These potential barriers are being addressed through government subsidy plans, continuing education to increase awareness, and being culturally sensitive when dealing with the Asian family.     

用原核增强子提高hTERT启动子介导的基因表达

目的:探讨原核增强子能否提高hTERT启动子的转录活性及对其肿瘤特异性的影响。方法:将增强子SV40、CMV分别或组合构建一系列GFP和荧光素酶报告基因载体,转染人肝癌、鼻咽癌、宫颈癌、结直肠癌细胞、成纤维肉瘤和正常成纤维细胞,流式细胞仪计数和双荧光酶分析系统检测基因的表达效率。结果:在正常成纤维细胞中这些载体均不能有效表达;而在肿瘤细胞中hTERT启动子能介导基因表达但效率不高,增强子能使基因表达增强3~26倍,特别是单独CMV增强子和SV40-CMV双增强子使荧光素酶表达提高20~26倍,是常用的CMV增强子/启动子的2~7倍;完整CMV增强子/启动子对hTERT启动子的活性影响因不同细胞而异。结论:增强子能显著增强hTERT启动子的转录活性并对其肿瘤特异性没有影响,CMV增强子或SV40-CMV双增强子/hTERT启动子是高效特异的通用调控元件,用于靶向性肿瘤基因治疗具有巨大潜力。     

中国人散发性大肠癌APEX基因氧化还原功能区中常见的单核苷酸多态性

目的 :了解散发性大肠癌中脱嘌呤 /脱嘧啶核酸内切酶 (apurinic/apyrimidinicendonuclease ,APEX ,Ape/Ref 1,HAP1)基因氧化还原功能区遗传变异状况。方法 :收集散发性大肠癌及相应癌周正常肠黏膜各 15 0例 ,抽提基因组DNA ;采用PCR扩增、变性梯度凝胶泳电泳 (denaturinggradientgelelec trophoresis ,DGGE)筛选、DNA测序的方法检测散发性大肠癌中APEX基因exon1、exon2和exon3的基因变异。结果 :4例exon1扩增片段DGGE图谱出现异常条带 ,经测序证实肿瘤及相应正常组织存在 4 5 3G→T巅换 ,基因型均为GT ;exon2未发现异常泳动条带 ;16例exon3扩增片段的DGGE图谱出现异常条带 ,测序发现exon3存在 12 4 7A→G转换 ,该变异导致APEX基因第 6 4位密码子由ATC变为GTC ,相应的氨基酸由异亮氨酸变为缬氨酸 ,肿瘤及癌周正常黏膜具有相同基因型。结论 :APEX基因氧化还原功能区 12 4 7A→G多态性在中国人散发性大肠癌中的频率远高于国外报道正常人群中的频率 ,可作为遗传流行病学研究的候选位点     

人源性食管鳞癌cDNA文库的构建及鉴定

目的:构建人源性食管鳞癌cDNA噬菌体表达文库。方法:从人食管鳞癌组织中提取总RNA并分离纯化mRNA,用RT-PCR合成cDNA单链,LD-PCR扩增双链cDNA,除去<500bp的小片段,与载体λTriplEx2噬菌体左右臂连接,经体外包装即构成全长cD-NA噬菌体表达文库。转化E.coliXL1-Blue感受态细胞,测定文库的滴度,确定文库的容量大小,用蓝白筛选测定文库的重组率,PCR鉴定cDNA插入片段的大小。结果:构建的人源性食管鳞癌cDNA噬菌体表达文库滴度为1.64×106pfu/mL,重组率为98.6%,cDNA插入片段的大小为0.7～2.5kb,平均长约1.5kb。结论:成功构建1个人源性食管鳞癌cDNA噬菌体表达文库,适合于大批量筛选cDNA克隆的食管鳞癌肿瘤抗原基因。     

Genetics and epigenetics of leukemia and lymphoma: from knowledge to applications,meeting report of the Josep Carreras Leukaemia Research Institute

The meeting, which brought together leading scientists and clinicians in the field of leukemia and lymphoma, was held at the new headquarters of the Josep Carreras Leukaemia Research Institute (IJC) in Badalona, Catalonia, Spain, September 19-20, 2019. Its purpose was to highlight the latest advances in our understanding of the molecular mechanisms driving blood cancers, and to discuss how this knowledge can be translated into an improved management of the disease. Special emphasis was placed on the role of genetic and epigenetic heterogeneity, and the exploitation of epigenetic regulation for developing biomarkers and novel treatment approaches.     

Variation in innate immunity genes and risk of multiple myeloma

Multiple myeloma (MM) is a B‐cell lymphoid malignancy suspected to be associated with immunologic factors. Given recent findings associating single‐nucleotide polymorphisms (SNPs) in innate immunity genes with non‐Hodgkin lymphoma, we conducted an investigation of innate immune gene variants using specimens from a population‐based case‐control study of MM conducted in Connecticut women. Tag SNPs (N = 1461) summarizing common variation in 149 gene regions were genotyped in non‐Hispanic Caucasian subjects (103 cases, 475 controls). Odds ratios (OR) and 95% confidence intervals (CI) relating SNP associations with MM were computed using unconditional logistic regression, while the MinP test was used to investigate associations with MM at the gene level. We calculated permutation‐adjusted P‐values and false discovery rates (FDR) to account for the number of comparisons performed in SNP‐level and gene‐level tests, respectively. Three genes were associated with MM when controlling for a FDR of ≤10%: SERPINE1 (P_MinP < 0.0001; FDR = 0.02), CCR7 (P_MinP = 0.0006; FDR = 0.06) and HGF (P_MinP = 0.001; FDR = 0.08). Two SNPs demonstrated robust associations: SERPINE1 rs2227667 (P = 2.1 × 10^?5, P_permutation = 0.03) and HGF rs17501108 (P = 5.0 × 10^?5, P_permutation = 0.07). Our findings suggest that genetic variants in SERPINE1 and HGF, and possibly CCR7, are associated with MM risk, and warrant further investigation in other studies. Copyright © 2010 John Wiley & Sons, Ltd.