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。     

NQO1基因多态性与肺癌遗传易感性

目的：探讨依赖还原型辅酶１／２醌氧化还原的酶基因ｃＤＮＡ６００位Ｃ→Ｔ点突变怕致物基因多态必理否与肺癌遗传多态性有关。方法：采用聚合酶锭反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）的分析方法分析队列 肺癌病人与１３６例健康成人对照组ＮＱＯ１的基因多态性。结果：Ｔ等位基因频率在肺癌组和对照组分别为５４％、４３％,两组有显著差异（Ｐ＝０．０２４）。基因型分布在肺癌组和组之间差异显著（Ｐ＝０．００８）     

DNA修复基因XRCC1多态性与肺癌易感性研究进展

X线修复交叉互补基因1（XRCC1）是一种重要的DNA修复基因，参与DNA单链断裂和碱基损伤修复，其编码的蛋白质在碱基修复过程中是不可缺少的。该基因的多态性会导致相应的氨基酸改变，从而影响DNA修复，可能引起肿瘤的易感性。XRCC1基因多态性与吸烟交互作用对肺癌易感性的关系仍然存在争论，其相关性需进一步深入研究。     

CYP1A1、GSTM1基因多态性与肺癌易感性的研究

目的:探讨CYP1A1、GSTM1基因多态性与肺癌易感性之间的相关性。方法:利用RFLP-PCR(限制性片段长度多态性-聚合酶链反应)方法检测65例原发性肺癌和60例非肿瘤患者CYP1A1、GSTM1基因,再用NcoI及HinfI两种内切酶识别CYP1A1等位基因亚型。结果:1)肺癌组与对照组CYP1A1等位基因型Ile/Ile、Ile/Val、Val/Val的频率总体分布无显著性差异;但肺癌组CYP1A1(Val/Val)基因型频率(18.5%)明显高于对照组(8.3%),两组差异有显著性(P<0.05)。2)肺癌组GSTM1(-)基因型的频率(63.1%)明显高于对照组(45.0%),P<0.05。3)两种等位基因联合分析发现,与携带CYP1A1(Ile/Ile)/GSTM1(+)基因型的个体相比:CYP1A1(Ile/Ile)/GSTM1(-)以及CYP1A1(Ile/Val+Val/Val)/GSTM1(+)基因型个体患肺癌的风险度较高,OR分别为3.82(95.0%CI,1.27～11.45)和3.5(95.0%CI,1.18～10.41);而CYP1A1(Val/Val)/GSTM1(-)基因型个体患肺癌的风险度最高,OR为10.5(95.0%CI,1.70～64.73)。4)进一步分层分析发现,CYP1A1(Ile/Val+Val/Val)等位基因型主要增加鳞癌的危险性;而GSTM1基因型组织类型无明显的相关性。5)在分析吸烟对肺癌易感性的影响时发现,CYP1A1(Ile/Val+Val/Val)及GSTM1(-)等位基因型与吸烟有协同作用,并与至发病时的累积吸烟量有关。结论:CYP1A1(Val/Val     

DNA修复基因ERCC1多态性与肺癌易感性的关系

背景与目的最近研究发现DNA修复基因多态性可以影响到肿瘤的易感性,因此通过不同的DNA修复基因可筛选出肿瘤的易感人群,从而有望达到肿瘤的早期预防、诊断和治疗。本研究旨在分析DNA修复基因ERCC1多态性及其与肺癌易感性的关系。方法采用病例-对照研究,收集上海肺科医院原发性肺癌患者291例为病例组,同期住院的非肿瘤患者273例作为对照组,并进行流行病学调查。应用Taqman探针结合实时荧光PCR方法分析病例组和对照组的ERCC1基因T118C的多态性分布,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对肺癌的交互作用。结果在不吸烟人群中,ERCC1基因118位点3种基因型在病例组和对照组人群中分布差异有统计学意义(χ2=11.19,P<0.01)。在不吸烟人群中,与携带野生纯合基因型(C/C)相比,携带突变纯合基因型(T/T)者患肺癌的风险会增加,其校正OR值为3.16(95%CI:1.29-7.73,P<0.01)。以携带野生纯合基因型(C/C)且不吸烟者作为参照,吸烟>25包-年且携带野生纯合基因型(C/C)或杂合基因型(C/T)者患肺癌的风险均会提高,其校正OR值分别为2.62(95%CI:1.54-4.44)、2.41(95%CI:1.36-4.26,P<0.01)。以携带野生基因型者作为参照,携带突变纯合基因型者患腺癌的风险度会增加,其OR值为2.29(95%CI:1.05-4.78,P=0.03)。结论DNA修复基因ERCC1118C/T多态性可能对肺癌易感性产生影响,并可能与吸烟有一定的协同作用。     

DNA修复基因多态性与肺癌易感性的研究进展

肺癌的发生与个体遗传易感性有关, 其中DNA修复基因多态性可以引起不同DNA损伤反应, 而机体间DNA损伤修复能力的不同与肺癌的发生有密切联系。DNA修复基因多态性与肺癌易感性的关系已成为当前的研究热点。本文回顾了DNA修复基因的作用机制及其多态性与肺癌易感性的国内外研究现状, 就DNA损伤和修复类型、DNA不同修复途径相关基因的作用机制及其多态性与肺癌易感性的关系、DNA修复基因多态性与肺癌化疗敏感性的关系几个方面进行综述。      

DNA修复基因单核苷酸多态性与肺癌易感性关系的研究进展

肺癌是人类最常见的恶性肿瘤，在工业化国家和我国许多城市(如上海、北京)已位居全部恶性肿瘤死因的首位。我国多数地区的肺癌发病率和死亡率在过去的20-30年间迅速增长，并继续保持这一增长趋势，成为严重危害我国人民身体健康的主要疾病之一。肺癌的发病机制尚未完全阐明，但许多研究证明其形成是一个多因素、多阶段的过程，是由于环境危险因素和个体遗传因素复杂交互作用的结果。     

MCP-1基因多态性与食管癌易感性的关系

目的：研究 MCP-1-2518位点基因多态性与济南地区汉族食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）易感性的关系。方法应用聚合酶链反应（PCR）和 DNA 直接测序方法对202例 ESCC 患者和265例健康对照进行 MCP-1-2518位点基因多态性检测。结果ESCC 患者 MCP-1-2518位点的多态性基因型和等位基因分布与健康对照组差异无统计学意义,P ＞0．05。根据吸烟状况的分层分析发现,与 GG 基因型相比,携带 AA 基因型可显著增加吸烟者的 ESCC 发病风险,经性别和年龄校正的 OR 值为3．064,95％CI 为1．397～6．718;而在非吸烟的患者和健康对照组之间差异无统计学意义,P ＞0．05。结论MCP-1-2518位点的多态性基因型和等位基因不单独影响 ESCC 的发生和发展, MCP-1-2518位点的 AA 基因型可增加吸烟人群 ESCC 易感性。     

p21WAF1基因多态性与胃癌易感性关系

目的:探讨p21WAF1基因缺失与多态性及其意义。方法:采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)法和链霉菌抗生物素蛋白-过氧化酶(SP)法分别检测胃癌中p21WAF1基因缺失与多态性和p21蛋白表达。结果:PCR扩增显示,30例胃癌和45例非胃癌标本均无p21WAF1第二外显子缺失。PCR-RFLP发现胃癌和正常胃粘膜p21第二外显子多态性分别为26.7%(8/30)和8.9%(4/45),有显著性差异(P<0.05),且8例具多态性胃癌标本中的正常胃粘膜亦具有这种多态性。p21蛋白阳性表达率,胃癌为43.3%(13/30),非胃癌为100%(45/45),两者有显著性差异(P<0.05),具p21WAF1基因多态性胃癌为37.5%(3/8),与无多态性胃癌45.5%(10/22)无相关性(P>0.05)。结论:胃癌中p21WAF1基因无缺失,而存在多态性。p21WAF1基因多态性和p21表达与胃癌发生有关,但两者无相关性。WAF1     

CYP2E1基因多态性与肺癌易感性关系的研究进展

肺癌是最常见的恶性肿瘤,其发生发展与吸烟、大气污染、危险因素暴露及基因变异等多种因素有关,由细胞色素P450(CYP450)基因家族所编码的细胞色素P450酶系(Cytochrome P450s)所组成的Ⅰ相酶介导氧化代谢,具有重要的解毒功能.CYP2E1是CYP450基因家族重要成员之一,大量研究表明其基因多态性与肺癌易感性密切相关,但研究结果不一致.     

EPHX1 gene polymorphisms and individual susceptibility to lung cancer

We investigated the roles of EPHX1 Tyr113His and His139Arg polymorphisms in lung cancer susceptibility in a Finnish study population comprising of 230 lung cancer cases and a large control group (n=2105). The controls were distributed into five age strata, which enabled us to examine the potential age-related changes in the putative EPHX1 at-risk genotypes in the cancer free population. Although the exon 3 slow activity associated allele (His113) containing genotypes posed a decreased lung cancer risk compared with the homozygous wild-type Tyr113/Tyr113 genotype (OR, 0.68; 95% CI, 0.49-0.94), no association was seen for the EPHX1 phenotypes interpreted from the combined exons 3 and 4 genotype data. Neither was any difference seen in the prevalence of the EPHX1 Tyr113His genotypes or interpreted EPHX1 phenotypes in the different age groups.     

中国汉族人群DNA聚合酶ε基因POLE1单核苷酸多态性与肺癌易感性的关系

目的：探讨人类DNA聚合酶ε基因POLE1单核苷酸多态性（SNP）与肺癌易感性间的关系。方法：采用病例对照研究方法,选择经组织学确诊的肺癌患者462例,以及相同地区,性别年龄频数匹配的对照466例,针对经筛选的5个SNP进行基因型检测,通过统计分析研究基因频率与肺癌风险的关系,并探讨吸烟在其中的影响。结果：病例组rs5744738基因频率分布高于对照组（P〈0.05）。A/A纯合变异携带人群的患肺癌风险显著降低（校正OR=0.47,95%CI：0.25～0.91）。在分层分析中,60岁以上人群患肺癌的风险显著下降（校正OR=0.28,95%CI：0.09～0.91）,无患肿瘤家族史人群下降到0.42倍（校正OR=0.42,95%CI：0.19～0.90）。随着吸烟量的增加,G/G或G/A基因型人群肺癌风险显著升高。rs5744962变异位点（T→C）可提高非吸烟人群的患肺癌风险至1.75倍（95%CI：1.02～3.00）。结论：选取的5个人类POLE1基因SNP的多态性可能与中国汉族人群肺癌遗传易感性有关,在携带rs5744738及与之紧密连锁的rs4883545、rs5744873突变纯合基因的人群,患肺癌的风险显著降低,而携带rs5744962、rs5745047突变基因位点的非吸烟人群患肺癌的风险升高。     

Single-nucleotide polymorphisms of LIG1 associated with risk of lung cancer

To investigate the association of LIG1 with the risk of lung cancer, all subjects of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital-based case–control study. The case group consisted of 370 histologically diagnosed lung cancer patients; 314 controls were selected from cancer-free patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan real-time PCR method. All statistical analyses were performed with Statistical Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency of LIG1 rs1050298 SNP displayed significant difference between the case and the control group. Individuals carrying the LIG1 rs1050298 T genotype had higher risks of lung cancer, especially those with squamous cell carcinoma.     

CHRNA3基因多态性与肺癌易感相关性分析

目的：探讨尼古丁乙酰胆碱受体基因CHRNA3多态性与肺癌易感性的关系。方法：采用以医院患者为基础的病例一对照研究方法,对2008-01-01-2011-06-30在江苏省肿瘤医院就诊原发性肺癌患者600例（病例组）和健康体检人员600名（正常对照组）,以TaqMan-MGB探针技术检测CHRNA3上的SNPs位点rs3743073（T〉G）基因型,比较组间基因型分布频率的差异。结果：肺癌患者CHRNA3rs3743073（T〉G）的TT、TG和GG基因型频率分别为20．7％、43．0％和36．3％,正常对照人群分别为31．0％、48．5％和20．5％,差异均有统计学意义,P〈0．05。肺癌患者CHRNA3rs3743073（T〉G）的A、G等位基因频率分别为42．2％和57．8％,正常对照人群分别为53．3％和44．8％,差异均有统计学意义,P〈0．05。与TT基因型患者相比,TG和GG基因型患者发生肺癌的风险分别增加1．132倍（95％CI：1．004～1．277,P=0．048）和1．663倍（95％CI：1．406～1．968,P=0．001）;rs3743073G（TG和GG）患者发生肺癌的风险增加1．290倍（95％CI：1．150～1．447,P=0．001）。年龄〉60岁、男性、吸烟的患者中,rs3743073G变异基因型的患者发生肺癌的危险性显著增加,P=0．05。结论：CHRNA3基因rs3743073G变异基因型发生肺癌的危险明显增加,尤其在年龄〉60岁、男性和吸烟患者中更为显著。     

Single nucleotide polymorphisms in breast cancer susceptibility gene 1 are associated with susceptibility to lung cancer

BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student''s t-test, a χ² test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.