XRCC1基因多态性与放射性损伤

X线修复交叉互补基因1(XRCC1)是一种重要的DNA修复基因,该基因的多态性会导致其编码蛋白相应的氨基酸改变,影响DNA修复,进而造成肿瘤患者的放射性损伤.目前研究发现,XRCC1单核苷酸多态性与肿瘤患者放射性损伤相关,但其相关性需进一步深入研究.     

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。     

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.     

BER通路DNA修复基因多态性与头颈肿瘤易感性的研究进展

碱基切除修复（base excision repair,BER）是DNA损伤修复的重要通路。大量研究文献提示BER通路作为DNA修复机制中重要的通路,其基因的多态性可能是头颈肿瘤诊断、治疗及预后中较重要的预测指标。本文对近年来BER通路修复重要基因（XRCC1和ADPRT）多态性与头颈肿瘤易感性的相关国内外文献进行总结发现,XRCC1的3处常见的单碱基突变可使XRCC1编码的蛋白质功能发生变化,使机体对癌症的易感性发生变化。ADPRT在正常组织中表达下降则提示DNA损伤不能有效地修复,在此基础上增加了基因组的不稳定性和发生突变的频率。此外,BER通路修复基因的多态性与其他头颈肿瘤,如鼻癌、喉癌、甲状腺癌之间的相关性还需进一步研究。     

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多态性与乳腺癌易感性

XRCC1是一个低度外显的基因，其编码的蛋白质在碱基切除修复过程中是不可缺少的。该基因多态性会导致所编码蛋白发生改变，从而影响DNA修复，可能引起肿瘤的易感性。XRCC1基因多态性与乳腺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。     

XRCC基因多态性与乳腺癌关系的研究进展

肿瘤的发生发展是由于多种因素共同作用所致,DNA的损伤是其中的重要原因之一。XRCC是X线修复交叉互补基因,参与DNA的修复过程。目前已经克隆的有单链断裂修复基因XRCC1和双链断裂修复基因XRCC2-7,有大量研究证明:它们的多态性与乳腺癌的易感性有着密切的相关性。本文就XRCC1-7与乳腺癌易感性的相关性进行综述。     

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基因多态性与肿瘤易感性的研究进展

X线修复交叉互补基因1(XRCC1)是一种重要的DNA修复基因.XRCC1基因中存在3个单核苷酸多态性位点,各位点多态对各种肿瘤易感性的影响不一.目前,XRCC1单核苷酸多态性与肿瘤易感性关系的研究结果之间存在分歧.     

修复基因XRCC1 Arg194Trp位点多态性与肝癌易感性的关系

目的:探讨DNA损伤修复基因XRCC1多态与肝癌遗传易感性的关系。方法:本研究选取了130例肝癌患者及130例性别、年龄相匹配的正常对照者进行研究,采用限制性片段长度多态性方法,比较不同基因型与肝癌发病的关系。结果:变异型等位基因XRCC1 Arg/Trp及Trp/Trp的出现率在肝癌组和对照组中分别是27.69%和10.77%,(P<0.05);而野生基因型XRCC1 Arg/Arg出现率在肝癌组和对照组中分别是72.31和89.23%,(P>0.05)。结论:XRCC1基因Arg194Trp位点单核苷酸多态在肝癌的发生过程中起着至关重要的作用。     

修复基因XRCC1 Arg194Trp位点多态性与肝癌易感性的关系

目的：探讨DNA损伤修复基因XRCC1多态与肝癌遗传易感性的关系。方法：本研究选取了130例肝癌患者及130例性别、年龄相匹配的正常对照者进行研究,采用限制性片段长度多态性方法,比较不同基因型与肝癌发病的关系。结果：变异型等位基因XRCC1 Arg/Trp及Trp/Trp的出现率在肝癌组和对照组中分别是27.69%和10.77%,（P〈0.05）;而野生基因型XRCC1 Arg/Arg出现率在肝癌组和对照组中分别是72.31和89.23%,（P〉0.05）。结论：XRCC1基因Arg194Trp位点单核苷酸多态在肝癌的发生过程中起着至关重要的作用。     

Tumor growth is suppressed in mice expressing a truncated XRCC1 protein

Tumor progression depends on the support of cells in the microenvironment, and is driven in part by the generation of reactive oxygen species (ROS). ROS can damage DNA, and the repair of damaged DNA is a well-known process involved in tumor initiation and promotion, but the role of DNA repair in tumor progression is not fully understood. In this regard the X-ray cross complementing 1 (XRCC1) protein is known to orchestrate the assembly of repair complexes at sites of DNA single strand breaks either directly or indirectly through repair of damaged bases, largely as the result of ROS-induced damage. XRCC1 polymorphisms have been shown to be associated with increased cancer. It was therefore of interest to investigate the effect of XRCC1 gene mutations on cancer progression. In an attempt to make XRCC1 point mutant mice, we generated a truncated protein (XRCC1tp) by the insertion of a neomycin cassette in intron12 of the XRCC1 gene. This unique finding allowed us to investigate cellular and tumor progression phenotypes in mice associated with expression and function of an altered XRCC1 protein on one allele. XRCC1tp cells showed increased toxicity to MMS, enhanced MMS-induced depletion of NADH suggesting increased PARP activity, and normal functional repair of MMS-induced DNA damage. Six months following treatment with the alkylating carcinogen azoxymethane (AOM) at 10 mg/kg once a week for 6 weeks, XRCC1tp mice had a decrease in average colon tumor volume of 14±3 mm(3) compared to 34±4 mm(3) in WT littermates (p ≤ 0.03, N= 20/genotype). XRCC1tp mice had a 72 per cent decrease in B16 melanoma tumor burden compared to wt littermates. Average tumor volume in transgenic PyMT metastatic breast cancer mice expressing XRCC1tp was 359 cubic mm in PyMT mice expressing XRCC1tp compared to 730 cubic mm in PyMT mice expressing XRCC1wt (p ≤ 0.001, N= 20/genotype). These data suggest that the presence of an XRCC1 truncated protein alters XRCC1 function independent of DNA repair, and is associated with anti-tumor activity.     

Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer

DNA repair has an essential role in protecting the genome from damage by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer. We have compared the frequency of polymorphisms in the NER genes, XPD, XPF, XPG, ERCC1; in the BER gene, XRCC1; and in the RR gene, XRCC3; in colorectal cancer patients and in a control group. No significant associations were found for any of the NER gene polymorphisms or for the XRCC1 polymorphism. The C allele (position 18067) of the XRCC3 gene was weakly but significantly associated with colorectal cancer (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=0.03). For all patients who were heterozygous for any of the repair genes studied, tumour tissue was investigated for loss of heterozygosity (LOH). Only one example of LOH was found for all the genes examined. From the association and LOH data, we conclude that these genes do not have an important role in protection against colorectal carcinogenesis.     

XRCC 1多态性与肿瘤化疗敏感性和预后的研究

化疗是恶性肿瘤最重要的治疗手段,对肿瘤化疗耐药机制以及化疗效果预测一直是肿瘤学研究的热点.DNA修复能力是影响化疗疗效的重要因素,修复基因的单核苷酸多态性可改变修复能力,X线修复交叉互补基因1(XRCC1)是参与DNA修复的重要成分,检测XRCC 1基因的单核苷酸多态性可以预测治疗疗效.     

XRCC 1多态性与肿瘤化疗敏感性和预后的研究

化疗是恶性肿瘤最重要的治疗手段,对肿瘤化疗耐药机制以及化疗效果预测一直是肿瘤学研究的热点.DNA修复能力是影响化疗疗效的重要因素,修复基因的单核苷酸多态性可改变修复能力,X线修复交叉互补基因1(XRCC1)是参与DNA修复的重要成分,检测XRCC 1基因的单核苷酸多态性可以预测治疗疗效.     

Genetic Variation in a DNA Double Strand Break Repair Gene in Saudi Population: A Comparative Study with Worldwide Ethnic Groups

DNA repair capacity is crucial in maintaining cellular functions and homeostasis. However, it can be alteredbased on DNA sequence variations in DNA repair genes and this may lead to the development of many diseasesincluding malignancies. Identification of genetic polymorphisms responsible for reduced DNA repair capacity isnecessary for better prevention. Homologous recombination (HR), a major double strand break repair pathway,plays a critical role in maintaining the genome stability. The present study was performed to determine thefrequency of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian population incomparison with epidemiological studies by “MEDLINE” search to equate with global populations. The variantallelic (T) frequency of XRCC3 (C>T) was found to be 39%. Our results suggest that frequency of XRCC3 (C>T)DNA repair gene exhibits distinctive patterns compared with the Saudi Arabian population and this mightbe attributed to ethnic variation. The present findings may help in high-risk screening of humans exposed toenvironmental carcinogens and cancer predisposition in different ethnic groups.     

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