XRCC1基因多态性对结肠癌患者术后FOLFOX4方案化疗疗效的影响

目的 探讨X射线交错互补修复基因1(XRCC1) Arg399Gln基因多态性对结肠癌患者术后FOLFOX4方案化疗疗效的影响.方法 113例结肠癌患者均接受根治术治疗.术后采用焦磷酸测序法检测肿瘤组织中的XRCC1Arg399Gln基因多态性,并给予FOLFOX4方案化疗6个周期.治疗结束后对患者进行随访.结果 (1)113例结肠癌患者的XRCC1 Arg399Gln位点包括Gln/Gln、Gln/Arg、Arg/Arg等3种等位基因型,其频率分别为66.4％(75/113)、27.4％(31/113)、6.2％(7/113).(2)Gln/Gln基因型组与非Gln/Gln基因型组之间性别、年龄、病理类型、癌肿部位、肿瘤形态、TNM分期、T分期、癌胚抗原(CEA)相比差异无统计学意义(P＞0.05).(3)随访期内,Gln/Gln基因型组复发转移率显著低于非Gln/Gln基因型组,3年生存率显著高于非Gln/Gln基因型组,差异有统计学意义(P＜0.05).结论 XRCC1Arg399Gln基因多态性可以影响结肠癌患者术后FOLFOX4辅助化疗的远期疗效.     

XRCC1基因单核苷酸多态性与食管癌易感性的关系

目的探讨X线修复交叉互补基因(X-ray cross complementing group1,XRCC1)单核苷酸多态性(single nucleotide polymorphism,SNPs)与食管癌易感性及临床病理的关系。方法应用Sequenom MassARRAY时间飞行质谱系统对200例食管癌及200例对照者XRCC1基因10个多态位点进行基因型分型。统计分析基因型频率和食管癌易感性的关系,统计基因多态与食管癌临床病理之间的关系。结果 XRCC1基因10个多态位点,rs25491位点、rs3213242位点没有多态性。条件Logistic回归分析显示,rs25487位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.020-2.381,P=0.040);rs1799778位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.019-2.381,P=0.041);rs2682585位点基因频率在病例组和对照组间差异有统计学意义(OR=14.313,95%CI=5.188-39.489,P=0.000);其余位点两组间差异无统计学意义。没有发现有意义的单体型。未发现基因多态与食管癌临床病理特征之间的关系。结论 XRCC1基因SNP位点rs2682585、rs25487和rs1799778与食管癌发病风险有显著相关性,很可能是决定食管癌个体遗传易感性的重要因素,以上3个SNP位点与食管癌临床病理特征之间无相关性。     

BER通路中XRCC1多位点单核苷酸多态性与新疆不同民族喉癌易感性相关性研究

背景与目的:影响肿瘤遗传易感性的修复基因主要存在修复通路碱基切除修复(base excision repair,BER)途径,而X射线交错互补修复基因1(X-ray repair cross complementing group 1,XRCC1)是BER通路中的核心基因。近几年,国内外开展了许多有关基因多态性和喉癌易感性的研究。探讨BER通路DNA修复基因XRCC1多位点单核甘酸多态性与新疆不同民族喉癌易感性关系。方法:采用患者组与对照组的研究方法,选择58例喉癌(经病理证实为鳞状细胞癌)患者和120名体检正常的健康人对照,应用Multiplex SNa Pshot技术检测DNA碱基切除修复基因XRCC1的Gln632Gln(rs3547)、Arg399Gln(rs25487)、Arg280His(rs25489)、Arg194Trp(rs1799782)位点单核苷酸多态在患者组和正常对照组中的分布情况。结果:喉癌患者组中XRCC1Arg280His(rs25489)C/T(杂合型)及T/T(突变型)基因型的比例与对照组比较差异无统计学意义(P>0.05)。喉癌患者组中XRCC1的其余3个位点Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型的比例明显高于对照组(P<0.01)。其中汉、维、哈3个民族患者组Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型比例显著高于对照组(P<0.05),携带(rs3547)C/T及T/T基因型、(rs25487)C/T及T/T基因型、(rs1799782)G/A及A/A基因型个体较携带XRCC1(rs3547)C/C基因型、(rs25487)C/C基因型、(rs1799782)G/G基因型的个体患喉鳞状细胞癌的风险升高了分别为0.96倍、1.74倍、1.39倍;1.47倍、1.32倍、0.77倍,1.49倍、1.51倍、1.56倍。结论:汉、维、哈3个民族的XRCC1 Gln632Gln、Arg399Gln、Arg280His、Arg194Trp位点的单核苷酸多态性可能与喉癌遗传性有关联且有差异,XRCC1基因中的Gln632Gln、Arg399Gln、Arg194Trp位点的突变将导致喉癌的发病风险升高。而XRCC1基因中的Arg280His位点突变与喉癌发病的差异无统计学意义,可能该位点的突变与喉癌发病无关。     

XRCC1单核苷酸多态性与结直肠癌风险的关系

背景与目的:X线交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)编码蛋白在DNA单链断裂修复和DNA碱基修复过程中起重要作用.该基因外显子多态性的存在可影响编码蛋白的功能活性,最终使机体对癌症的易感性发生变化.本研究旨在探讨该基因外显子最常见的3处单核苷酸多态(single nucleotide polymorphism,SNP)--C26304T、G27466A和G28152A与结直肠癌风险的关系.方法:以聚合酶链反应(polymerase chain reaction,PCR)和限制性片段长度多态性(restrictive fragment length polymorphism,RFLP)分析方法,检测207例结直肠癌病例和621例成组匹配的正常对照XRCC1 C26304T、G27466A和G28152A基因型,并比较不同基因型与结直肠癌风险的关系.采用EH Linkage Software 1.2统计分析软件对研究对象的单体型分布进行预测.结果:年龄、性别、身体质量指数(body mass index,BMI)等个体特征,以及吸烟、饮酒等常见环境暴露因素的分布和/或构成比在结直肠癌病例组和对照组间差异均无显著性(P＞0.05).对XRCC1各多态基因型检测分型发现,结直肠癌病例组携带26304T、27466A和28152A变异等位基因的频率分别为29.95%、11.22%和28.22%,对照组分别为32.87%、12.34%和27.27%,各多态等位基因在两组间分布均没有显著性差异(P＞0.05).各多态基因型分布经x2拟合优度检验均符合Hardy-Weinberg平衡定律,且在两组间都没有显著性差异(P＞0.05).没有观察到各多态基因型与结直肠癌发病风险存在显著相关关系(P＞0.05).单体型分析发现,各变异等位基因在病例组和对照组内均存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型,其在两组的分布频率总和分别为95.54%和96.64%,然而在两组间同样不存在显著性差异(P＞0.05).结论:我国浙江省嘉善县人群中,XRCC1 C26304T、G27466A和G28152A基因多态性与结直肠癌发病风险不存在相关性,然而各变异等位基因存在遗传连锁不平衡现象,CGG、CGA、CAG和TGG是最常见的4类单体型.     

XRCC1基因多态与肿瘤遗传易感性研究进展

X射线交错互补修复基因1(XRCC1)通过直接与聚合酶β、DNA连接酶Ⅲ和多聚ADP核糖聚合酶形成复合物，共同参与因电离辐射和氧化损伤引起的碱基切除修复和单链断裂修复。XRCC1基因中存在3个单核苷酸多态位点，各位点多态对各种肿瘤遗传易感性的影响不一。现对XRCC1基因多态与某些肿瘤遗传易感性进行综述。     

XRCC1基因多态性与淋巴瘤发病风险的Meta分析

 目的运用Meta分析的方法综合评价DNA修复基因（X-ray repair cross-complementing group 1,XRCC1)的多 态性与淋巴瘤发病风险的关系。方法计算机检索PubMed、EMbase、中国期刊全文数据库、维普中文科技期刊数据库 、中国生物医学文献数据库,同时手工检索所有纳入文献的参考文献,收集截止到2010年2月关于XRCC1基因多态性 与淋巴瘤发病风险的病例对照研究,由两名研究者独立按照纳入标准筛选文献、提取资料并交叉核对,统计分析采 用RevMan5.0软件进行。结果共纳入11个病例对照研究,包括4 569例患者和5 746例对照。Meta分析结果显示： XRCC1 codon 399 基因型Gln/Gln、Arg/Gln和Gln/Gln+Arg/Gln与野生型Arg/Arg相比,频率差异均无统计学意义（ Gln/Gln vs. Arg/Arg:OR=1.04,95%CI［0.87,1.25］;Arg/Gln vs.Arg/Arg:OR=1.26,95%CI ［0.95,1.66］;Gln/Gln+Arg/Gln vs.Arg/Arg:OR=1.02,95%CI ［0.91,1.13］）,Gln/Gln+Arg/Gln基因型则有可 能增加霍奇金淋巴瘤的发病风险（OR=1.31,95%CI［1.02,1.69］）,XRCC1 codon280和XRCC1 codon 194的基因多 态性在患者和对照组之间的差异无统计学意义（XRCC1 codon280 His/His+Arg/His vs.Arg/Arg:OR=0.97,95%CI ［0.69,1.38］;XRCC1 codon 194 Trp/Trp+Arg/Trp vs.Arg/Arg:OR=1.01,95%CI［0.78,1.32］）。结论DNA修复 基因XRCC1的基因多态性与非霍奇金淋巴瘤发病风险没有相关性,codon399位点的Gln/Gln+Arg/Gln基因型则有可能 增加霍奇金淋巴瘤的发病风险。     

XRCC1基因多态性与食管鳞癌放疗敏感相关性分析

目的 了解食管鳞癌患者的X射线交错互补修复基因1(X-ray repair cross complementing group1,XRCC1)的4个单核苷酸多态性(single nucleotide polymorphisms,SNP)位点的分布情况及其与放疗敏感性的关系.方法 提取175例食管鳞癌患者外周血DNA,通...     

RASSF1基因单核苷酸多态性与食管癌的发病风险

目的:探讨RASSF1基因第三外显子G133T和第六外显子A315G单核苷酸多态性(SNP)与陕西地区汉族人群食管鳞状细胞癌(ESCC)易感性的关系.方法:采用基于人群的病例对照研究,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测120例ESCC和122例健康对照个体RASSF1基因多态位点的基因型频率分布,比较不同基因型与ESCC发生风险的关系.结果:RASSF1基因G133T多态的T等位基因频率和A315G多态的G等基因频率在ESCC患者组分别为17.5%和23.8%,显著高于健康对照组的6.1%和11.9%.根据个体吸烟状况进行分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和携带A/G基因型或G等位基因(A/G+G/G基因型)可显著增加吸烟个体ESCC的发病风险,经性别、年龄、GIC家族史校正后的OR值分别为11.7和5.02(95%CI=3.95-34.9和2.09-12.06).GIC家族史分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和A/G基因型可显著增加GIC家族史阳性个体和GIC家族史阴性个体ESCC的发病风险, 经性别、年龄、吸烟状况校正后的OR值为5.08和3.51(95%CI=1.85-13.92和1.69-7.21).结论:携带RASSF1基因G133T多态的T等位基因(G/T+T/T基因型)可能显著增加陕西地区人群ESCC的发病风险.携带RASSF1基因A315G多态的G等位基因(A/G+G/G基因型)可能显著增加陕西地区人群ESCC的发病风险.     

XRCC1单核苷酸多态性与含铂类药物化疗对肝肾功能影响相关性分析

目的探讨X射线损伤修复交叉互补基因1单核苷酸（XRCC1）多态性与恶性肿瘤患者铂类药物化疗前后肝肾功能变化的关系。方法化疗前采集外周静脉血,采用多聚酶链反应一高温连接酶反应（PCR—LDR）,进行XRCC1 Arg399Gln基因多态性的分型,观察化疗前后患者胆红素、转氨酶、蛋白、GGT、碱性磷酸酶、尿素氮、肌酐、尿酸等多项指标改变情况。结果携带XRCC1 399 Gln/Gln基因型患者,含铂类药物化疗前后总蛋白量的改变幅度低于XRCC1 399 Arg/Gln和XRCC1 399 Arg/Arg者;携带XRCC1 399 Arg/Gln基因型患者,含铂类药物化疗前后尿酸的变化高于XRCC1 399 Gln/Gln和XRCC1 399 Arg/Arg者;含铂类药物化疗前后其余各项肝肾功能指标的变化与XRCC1 Arg 399Gln单核苷酸多态性无关。结论 XRCC1单核苷酸多态性与含铂类药物化疗前后肝肾功能的改变无明显相关性。     

DNA修复基因XRCC1多态性与肺癌易感性的关系

目的:研究碱基切除修复基因XRCC1多态性与肺癌易感性的关系。方法:采用病例-对照研究,收集太原市原发性肺癌患者111例为病例组,同时随机抽取210名健康居民作为对照组,并进行流行病学调查。应用PCR-RFLP方法分析由内切酶MspI识别XRCC1基因Arg399Gln位点的多态性,比较不同基因型与肺癌易感性的关系,以及基因多态性与吸烟之间对肺癌易感性的交互作用。结果:XRCC1密码子399杂合基因型Arg/Gln可能对鳞癌有较弱的保护效应,并可能降低吸烟者患肺癌的危险性。而纯合突变基因型Gln/Gln与和吸烟的存在协同作用可显著提高肺癌的危险度。结论:碱基切除修复基因XRCC1密码子399的多态性可能会对肺癌易感性产生影响,并可能与吸烟量之间存在一定的协同作用。     

B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related geneticfactors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducteda hospital based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms(SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T,ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCAcases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design48-Plex SNPscanTM Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased riskof GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicateda significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males,older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that thefunctional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our resultswere limited by small sample size. Future larger studies are required to confirm our current findings.     

贲门腺癌中RASSF1A基因的甲基化状态及表达

 目的 研究贲门腺癌（gastric cardiac adenocarcinoma,GCA）中RASSF1A基因的甲基化状态及其蛋白表达情况。 方法 分别应用甲基化特异性PCR（MSP）、RT-PCR及免疫组织化学SP法检测贲门癌组织及相应癌旁组织的RASSF1A甲基化情况和mRNA水平及蛋白表达情况。 结果 92例贲门癌组织中有54例发生了甲基化,甲基化率为58.7%,显著高于癌旁正常组织（P<0.01）。Ⅲ期和Ⅳ期贲门癌患者中RASSF1A基因发生甲基化的比率显著高于Ⅰ期和Ⅱ期患者（P<0.05）。92例贲门癌组织中有43例RASSF1A基因蛋白表达阴性,与相应癌旁正常组织相比有显著性差异（P<0.01）。Ⅲ期和Ⅳ期贲门癌RASSF1A基因蛋白表达显著低于Ⅰ期和Ⅱ期患者（P<0.05）。发生甲基化的贲门癌组织中RASSF1A的mRNA水平的表达显著低于未发生甲基化的贲门癌组织（P<0.01）。 结论 RASSF1A基因启动子区发生甲基化导致的基因沉默可能是贲门腺癌发生的机制之一。     

p16基因C540G和C580T多态与高发区食管癌和贲门癌发病风险的关联

目的探讨p16基因第3外显子3’端非编码区C540G和C580T两个单核苷酸多态与河北省高发区食管鳞状细胞癌（ESCC）和贲门腺癌（GCA）遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法分析265例ESCC患者、238例CA;A患者和246名健康对照的p16基因C540G和C580T多态位点的基因型。结果p16基因C540G三种基因型（C／C、C／G、G／G）的频率分布在ESCC、GCA患者和对照组相比均无显著差异;p16基因C580T三种基因型（C／C、C／T、T／T）的频率在对照组和ESCC、GCA患者组间也无显著差异（P均〉0．05）。单体型分析显示,对照组540C／580C、540C／580T、540G／580C和540G／580T单体型的频率分别为80．1％、10．4％、8．5％和1．0％,ESCC组单体型频率（80．8％、9．6％、8．7％和0．9％）和GCA组的单体型频率（80．2％、9．2％、9．5％和1．1％）与之相比均无显著差异（P均〉0．05）。结论p16基因C540G和C580T多态可能与河北省高发区ES-CC和GCA的易感性无关。     

TSP1基因G1678A和A2210G基因多态性与贲门腺癌发病风险的关联

目的探讨凝血酶敏感蛋白-1(TSP1)基因第10外显子G1678A和第13外显子A2210G单核苷酸多态性（SNP）与中国北方人群贲门腺癌（GCA）遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测145名GCA患者和198名健康对照的TSP1 G1678A和A2210G多态性分布情况。结果TSP1 G1678A多态性位点的基因型及等位基因型频率在贲门腺癌患者组和对照组之间,其总体分布差异均无统计学意义（P>0.05）。根据吸烟状况和上消化道肿瘤家族史分层分析发现,与GG和GA基因型相比,携带AA基因型可能增加非吸烟个体贲门腺癌的发病风险（经性别、年龄和上消化道肿瘤家族史校正后的OR为1.79, 95%CI为1.46~2.11）。TSP1 A2210G位点G等位基因频率在对照组人群中<1%,它可能不是我国北方人群中的常见多态。结论TSP1基因第10外显子AA基因型可能是影响我国北方人群中非吸烟个体贲门腺癌发病风险的因素之一。     

Association of the XRCC1 c.1178G>A Genetic Polymorphism with Lung Cancer Risk in Chinese

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA baseexcision repair pathway which may influence the development of lung cancer. This study aimed to evaluatethe potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The createdrestriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluatethe XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associationsbetween the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regressionmodel. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantlydifferent from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increasedrisk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001).The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested thatthe XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinesepopulation.     

Association Between Single Nucleotide Polymorphisms in the XRCC1 Gene and Susceptibility to Prostate Cancer in Chinese Men

Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. TheX-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. Thepurpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations withsusceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: Thec.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility toprostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, χ2=12.36,P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, χ2=4.04, P=0.045), dominantmodel (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, χ2=9.12, P=0.003), recessive model (GG versus AG+AA:OR=2.17, 95% CI 1.33-4.06, χ2=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42,χ2=14.67, P<0.000). Conclusions: These findings suggest that the c.910A>G polymorphism of the XRCC1 geneis associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.     

Association of Helicobacter pylori Infection with Gastric Adenocarcinoma

Gastric adenocarcinoma is the most prevalent cancer in South Korea, and Helicobacter pylori (H. pylori) infection is also common. This study was performed to examine the association between H. pylori infection and gastric cancer, taking into account various other factors. To investigate the association between gastric adenocarcinoma and H. pylori infection, determined by urease-positive reaction in the CLO test, a total of 175 paired specimens (175 tumor and 175 tissues adjacent to tumor) of stomach cancer patients and a total of 113 control specimens were obtained. The positive H. pylori infection rates were 78.9% (138/175) among the patients in specimens of tumor or tissues adjacent to the tumor and 41.6% (47/113) among controls in the CLO test. A positive correlation between H. pylori infection and gastric cancer was observed (age-adjusted odds ratio, 7.0; MH χ²=34.5 with P <0.0005). These data suggest that stomach cancer patients in Korea have high infection rates of H. pylori regardless of site specificity, and this infection might be causally associated with stomach cancer.     

Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation andmetastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) andprevious studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, wetested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes inpatients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixedparaffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 werestudied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between singlenucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existenceof a significant relationship between tumor recurrence and overall survival was proved in this study, with at least oneallele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These resultsprovide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients.This result could help identify individuals with GC who have a high risk of tumor recurrence.