X射线损伤修复交叉互补基因1多态性与非吸烟女性肺癌易感性的关系

目的探讨X射线损伤修复交叉互补基因1（XRCCl）单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法采用以医院患者为基础的病例一对照研究方法,非吸烟女性肺癌患者50例,非癌对照50例。以聚合酶链反应一限制性片段长度多态性（PCR—RFLP）方法检测XRCC1基因Arg399Gln多态性,计算各基因型的比值比（OR）,并探讨烹饪油烟暴露史与多态基因型交互作用对肺癌患癌风险的影响。结果肺癌组与对照组XRCC1 Arg399Gln多态基因型分布差异无统计学意义（P〉0．05）,而腺癌组基因型分布与对照组差异有统计学意义（P〈0．05）。相对于399Arg／Arg基因型,携带至少1个Gin等位基因的个体患肺腺癌的调整OR值为2．19（95％CI为0．73～6．61）,而XRCC1 399Gin／Gin基因型携带者的调整OR值为14．12（95％CI为2、14～92．95）。携带至少1个399Gln等位基因的烹饪油烟暴露者患肺腺癌的风险明显升高,调整OR值为6．29（95％c,为1．99～19、85）。结论XRCC1基因Arg399Gln多态可能是非吸烟女性肺腺癌的遗传易感因素,399Gln等位基因与烹饪油烟交互作用,可提高非吸烟女性肺腺癌的发病风险。     

XPD基因多态性与非吸烟女性肺癌易感性的关系

背景与目的 着色性干皮病互补基因D（xeroderma pigmentosum group D，XPD）是一种重要的DNA损伤修复基因，其常见的多态是位于751密码子的A→C多态。本研究旨在探讨XPD基因751位点单核苷酸多态性与非吸烟女性肺癌易感性的关系，并探讨油烟暴露与基因多态性交互作用对肺癌风险的影响。方法 采用病例-对照研究方法，纳入非吸烟女性肺癌患者105人和对照105人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln多态基因型。结果 携带至少1个751Gln等位基因者患肺癌的风险显著增高，调整OR为2．80（95％CI为1．21～6．48）。携带等位基因751Gln又有油烟暴露的个体患肺癌的风险较两个危险因素单独作用时更高，校正OR为6．85（95％CI为1．69～27．67，P=0．007）。结论 XPD基因Lys751Gln多态是非吸烟女性肺癌的遗传易感因素。携带XPD751Gln等位基因又有油烟暴露的非吸烟女性患肺癌的风险明显增高。     

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。     

XRCC1基因多态性与肺癌易感性关系的研究进展

X射线损伤修复的交叉互补基因(X-ray repair cross complementing group 1，XRCC 1)是一种DNA损伤修复基因，其多态性能够改变DNA修复功能和效率，影响肿瘤易感性。分析了XRCCl基因结构、功能及其多态性与肺癌易感性的关系。     

XRCC1基因多态性与肺癌易感性关系的研究进展

X射线损伤修复的交叉互补基因 (X rayrepaircrosscomplementinggroup 1,XRCC1)是一种DNA损伤修复基因 ,其多态性能够改变DNA修复功能和效率 ,影响肿瘤易感性。分析了XRCC1基因结构、功能及其多态性与肺癌易感性的关系     

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。     

DNA损伤修复基因XRCC和hOGG1多态性与肺癌易感性的关系

DNA损伤修复基因的多态性能够改变DNA修复功能和效率,影响肿瘤易感性.许多研究报道DNA损伤修复基因多态性可能与肿瘤易感性有关,其突变在多种肿瘤的发生、发展过程中起着重要作用.另外,DNA损伤修复基因可能与其他基因相互作用,共同影响肿瘤的发生、发展.肺癌是目前在这方面被研究得最多的肿瘤.文章就DNA损伤修复基因XRCC和hOGG1多态性的生物学特点以及这些基因单核苷酸多态性与肿瘤易感性等方面进行了综述,为该基因用于肿瘤的预防、诊治提供理论借鉴.     

室内空气污染与非吸烟女性肺腺癌

 室内空气污染与非吸烟女性肺腺癌林春艳，孙喜文，林英姬，石于波，戴旭东近年来，肺癌发病率和死亡率在世界范围内迅速上升，女性肺癌的增长较男性更为突出。     

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。     

DNA修复基因XPD 312 Asn和751Lys多态性与非吸烟女性肺癌的关系

目的 着色性干皮病互补基因D(xeroderma pigmentosum group D,XPD)是一种重要的DNA损伤修复基因,其常见的多态是位于751密码子的A→C颠换和312密码子G→A转换。本研究旨在探讨XPD基因751位点和312位点单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法 采用病例-对照研究方法,纳入非吸烟女性肺癌患者222人和对照222人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln和Asp312Asn多态基因型。结果 携带至少1个751Gln等位基因者和携带至少1个312Asn等位基因者患肺癌的风险均显著增高,调整OR分别为3.36(95%CI为2.29-4.90)和1.83(95%CI为1.16-2.91)。结论 XPD基因Lys751Gln和Asp312Asn多态是非吸烟女性肺癌的遗传易感因素。     

Association of DNA repair gene XRCC1 polymorphisms with head and neck cancer in Korean population

Squamous cell carcinoma of the head and neck (SCCHN), which is relatively prevalent in Korea, is believed to be induced by environmental carcinogens and host genetic factors. Accumulating evidence has shown that genetic differences in DNA repair capacity resulting from genetic polymorphism influence the risk of environmental carcinogenesis. We therefore examined the associations of genetic polymorphisms in the DNA repair genes XRCC1 with the risk of SCCHN in a Korean population (hospital-based, case-control study; 147 cases and 168 controls). Three known polymorphisms in the XRCC1 gene were genotyped: R194W(C>T) in exon 6, R280H(G>A) in exon 9 and R399G(G>A) in exon 10. Although no significant associations were apparent with R280H(G>A) and R399G(G>A), a highly significant association (p = 0.0005) of R194W(C>T) with the increased risk (OR = 2.61; 95% CI 1.53-4.46) of SCCHN was detected among patients and normal controls under dominant model. The frequency of minor allele-containing genotypes (TT and CT) was much higher in SCCHN patients (51.8%) compared to that in normal controls (30.3%) (p = 0. 0005). When considering a relatively small number of cases (n = 147) and controls (n = 168) in our study, larger studies are needed to validate the genetic effects of XRCC1 polymorphisms in Asian populations. In conclusion, the result from our study provides additional evidence of an association of the XRCC1 polymorphism (Arg194Trp) with SCCHN as markers of genetic susceptibility in the Korean population.     

非小细胞肺癌NP方案化疗敏感性与DNA修复基因XRCC1多态性的关系

背景与目的:基因多态预测肿瘤化疗药物敏感性对肿瘤个体化治疗具有重要意义。本研究旨在探讨DNA修复基因XRCC1 codon194及399位点基因多态性与非小细胞肺癌长春瑞滨加顺铂(vinorelbine and cisplatin,NVB and DDP,NP)方案化疗敏感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术检测164例非小细胞肺癌患者外周血DNAXRCC1194和399位点的多态性。选择NP方案化疗,化疗两周期后评价疗效,并分析化疗敏感性与基因多态性的关系。结果:携带XRCC1基因Codon194C/T+T/T基因型者化疗有效率(41.8%)是C/C基因型者(26.0%)的2.038倍(P=0.036,95%CI=1.044-3.976)。携带XRCC1基因Codon399G/G、A/G、A/A型的患者化疗有效率(37.1%,34.6%,14.3%)之间的差异无统计学意义(P>0.05)。应用分析软件SHEsis发现以     

Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma

Background: The XRCC1 gene encodes the XRCC1 protein, which complexes with three other DNA repair enzymes involved in the base-excision repair (BER) pathways. Different XRCC1 polymorphisms may increase the risk of cancers by impairing interaction with other enzymatic proteins and consequently altering DNA repair activity, and result in carcinogenesis. Our study aimed to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280 and 399 and potential glioma risk. Methods: We collected 127 patients with primary glioma and 249 controls who requested general health examinations from Union Hospital of Tongji Medical College hospital from March 2007 to September 2010. A total of 5 ml venous blood was drawn from each subject. The polymorphisms of XRCC1 gene at codons 194, 280 and 399 were analyzed based on duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method. Results: The homozygous Trp/Trp and heterozygotes Arg/Trp variants of codon 194 had a 2.12 fold and 1.46 fold increased risk of glioma compared to the homozygous Arg/Arg wide genotypes. The same effect was found in codon 399, the codon 399 Gln/Gln and Arg/Gln genotypes being associated with a 2.24 fold and 1.67 fold increased risk in glioma. When comparing the codon 194 Arg/Arg and 399 Arg/Arg genotypes, the combination of codon 194 Trp allele and 399 Gln allele had a heavy increase in glioma risk (OR=2.87, 95%CI=1.56-6.73). Conclusion: The present study provided evidence of a potential role for XRCC1 codon 194 and 399 polymorphisms in genetic predisposition to glioma among the Chinese population. This analysis of correlation of DNA repair genes and glioma may provide a deeper insight into the genetic and environment factors for cancer risk.     

XRCC1基因Arg399Gln多态性与中国人群神经胶质瘤易感性Meta分析

目的:探讨XRCC1基因Arg399Gln (G/A)多态性与中国人群神经胶质瘤易感性的关系.方法:计算机检索Pubmed、EMBASE、中国知网、万方期刊、维普等中英文数据库,检索2014年10月之前公开发表的相关文献,对符合标准的文献采用NOS量表评价文献质量,应用RevMan5.1软件进行Meta分析.结果:共纳入9篇与XRCC1基因Arg399Gln多态性与神经胶质瘤易感性相关的病例对照研究,包括7 131例患者,其中病例组3 428例,对照组3 703例,NOS评分≥6分为高质量文献,仅2项研究质量评分＜6.Meta分析结果显示携带A等位基因可增加中国人群神经胶质瘤的患病风险(OR=1.20,95％CI:1.04～1.38,P=0.01).结论:中国人群中XRCC1基因Arg399Gln (G/A)多态性与神经胶质瘤的易感性存在相关性.     

DNA repair gene polymorphisms and benefit from gefitinib in never-smokers with lung adenocarcinoma

BACKGROUND:

The objective of this study was to investigate whether polymorphisms in DNA repair genes affect clinical outcome of never‐smokers with lung adenocarcinoma (NSLA).

METHOD:

Common polymorphisms in the DNA repair genes ribonucleotide reductase M1 (RRM1), excision repair cross‐complementation group 1 (ERCC1), and x‐ray repair cross‐complementing group 1 (XRCC1) were genotyped in DNA samples from 158 patients among 313 NSLA who were randomized to receive either gefitinib or gemcitabine plus cisplatin (GP) as first‐line therapy. Immunohistochemistry for ERCC1 (n = 38) and direct sequencing of the epidermal growth factor gene (EGFR) (n = 42) were performed using tumor samples.

RESULTS:

Patients who had the XRCC1 arginine (Arg)/Arg polymorphism at codon 399 (399Arg/Arg) had a higher response rate to gefitinib (71% vs 36%; P = .002) and had more EGFR‐mutant tumors (82% vs 29%; P = .001) than patients who had the glutamine (Gln) allele. Patients who had the ERCC1 adenine‐adenine (AA) polymorphism at codon 8092 (8092AA) had a higher response to GP than patients who had the cytosine‐cytosine (CC) or the CA genotype (100% vs 44%; P = .043).When gefitinib was compared with GP, significantly longer progression‐free survival (PFS) was observed with gefitinib among patients who had the XRCC1 399Arg/Arg genotype (7.5 months vs 6.6 months; P = .013), the RRM1 2464 guanine‐guanine (GG) genotype (11.5 months vs 6.0 months; P = .004), and the ERCC1 8092CA genotype (7.5 months vs 6.4 months; P = .024). When the 3 genotypes were analyzed jointly, significantly longer PFS was observed with gefitinib among patients who had ≥2 genotypes (8.1 months vs 6.4 months; P = .009), whereas a trend for longer PFS was observed with GP among patients without the 3 genotypes (6.3 months vs 2.0 months; P = .06). In a multivariate Cox regression model, the greater number of specific genotypes independently predicted improved overall survival (hazard ratio, 0.5; 95% confidence interval, 0.3‐0.8; P = .006).

CONCLUSIONS:

Patients with the XRCC1 399Arg/Arg, RRM1 2464GG, and ERCC1 8092CA genotypes did benefit from gefitinib. Having more of these genotypes may predict favorable prognosis for NSLA. Cancer 2011. © 2011 American Cancer Society.