AIM: To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: Relevant studie...AIM: To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS: Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg's and Egger's tests did not find any obvious publication bias. CONCLUSION: The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.展开更多
Objective: The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCCI) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. M...Objective: The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCCI) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods: Immunohistochemistry (IHC) was used to evaluate XRCCI protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Among 612 patients staged II/III in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P=0.347) or DFS (P=0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P=0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P=0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P〈0.05). Though XRCCI plays an important role in DNA repair pathways, no significant relationship is found in XRCCI expression and OS among gastric cancer in our study. Conclusions: XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.展开更多
Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage cause...Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.展开更多
Objective: To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 (XRCC1) and the susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods: Relevan...Objective: To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 (XRCC1) and the susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods: Relevant case-control studies were enrolled in the meta-analysis. We applied Rev Man 4.2 software to pool raw data and test studies' heterogeneity and to calculate the incorporated odds ratio (OR) and 95% confidence interval (95% CI). Results: Our data showed that the OR for the Gln allele of the Arg399Gln polymorphism, compared with the Arg allele, was 1.35 (95% CI, 1.16-1.57; P〈0.0001) for childhood ALL patients. Similarly, the homozygous genotype Gln/Gln and heterozygous genotype Arg/Gln both significantly increased the risk of childhood ALL compared with the wild genotype Arg/Arg (OR =1.58; 95% CI, 1.13-2.21; P=0.008; OR =1.51; 95% CI, 1.21-1.87; P=0.0002). The dominant model of Arg399Gln was associated with childhood ALL risk (OR =1.54; 95% CI, 1.25-1.89; P〈0.0001). The ethnic subgroup analysis demonstrated that the Gln allele in all five ethnic groups was prone to be a risk factor for childhood ALL just with different degrees of correlation while Arg194Trp SNP showed a protective or risk factor or irrelevant thing in different races. Conclusions: XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.展开更多
OBJECTIVE: To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES: A systematic literature search of papers ...OBJECTIVE: To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES: A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were "glioma", "polymorphism", and "XRCC1 or X-ray repair cross-complementing group 1". References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION: Studies were identified according to the following inclusion criteria: case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger's test using Stata 12.0 software. MAIN OUTCOME MEASURES: Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS: Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gin/Gin + GIn/Arg versus Arg/Arg: OR = 1.26, 95%CI= 1.03-1.54, P = 0.02). In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive (OR = 1.46, 95%CI= 1.04-2.45, P = 0.03) and dominant models (OR = 1.40, 95%CI= 1.10-1.78, P = 0.007), and homozygote contrast (OR = 1.69, 95%CI= 1.17-2.45, P = 0.005), but not in Caucasian sub- jects. For association of the Arg194Trp (eight studies) and Arg280His (four studies) polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION: The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.展开更多
AIM: To evaluate the association between X-ray crosscomplementing gene 1 (XRCCl) genetic polymorphism Arg399Gln and gastric cancer risk by means of metaanalysis. METHODS: We searched PubMed and NCBI up to June 1, ...AIM: To evaluate the association between X-ray crosscomplementing gene 1 (XRCCl) genetic polymorphism Arg399Gln and gastric cancer risk by means of metaanalysis. METHODS: We searched PubMed and NCBI up to June 1, 2008. A total of 16 clinical trials and reports were identified, but only 8 trials qualified under our selection criteria. Statistical analysis was performed with the software program Review Manage, version 4.2.8. RESULTS: Of the 8 case-control studies selected for this meta-analysis, a total of 1334 gastric cancer cases and 2194 controls were included. For Arg399GIn, the Gin/Gin genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR = 0.92, 95% CI, 0.71-1.19; P = 0.51). Similarly, no associations were found in the recessive and dominant modeling (Gin/Gin vs Arg/GIn + Arg/Arg: OR = 0.96; 95% CI, 0.77-1.19; P = 0.70 and Gin/Gin + Arg/GIn vs Arg/Arg: OR = 0.90, 95% CI, 0.77-1.05; P = 0.18). CONCLUSION: No association is found between the XRCC1 polymorphism Arg399GIn and gastric cancer risk.展开更多
目的探讨XRCC1基因Arg194Trp、Arg399Gln单核苷酸多态性(SNP)与外生型宫颈鳞状细胞癌放疗敏感性的关系。方法选择经组织病理学确诊的外生型宫颈鳞状细胞癌患者73例。其中临床分期Ⅰ期4例,Ⅱ期36例,Ⅲ期30例,Ⅳ期3例。肿瘤直径≤4 cm 30...目的探讨XRCC1基因Arg194Trp、Arg399Gln单核苷酸多态性(SNP)与外生型宫颈鳞状细胞癌放疗敏感性的关系。方法选择经组织病理学确诊的外生型宫颈鳞状细胞癌患者73例。其中临床分期Ⅰ期4例,Ⅱ期36例,Ⅲ期30例,Ⅳ期3例。肿瘤直径≤4 cm 30例,肿瘤直径>4 cm 43例;A点剂量≤80 Gy者36例,A点剂量>80 Gy者37例。近期疗效为完全缓解者(CR组)47例,部分缓解者(PR组)26例。采用错配扩增聚合酶链式反应检测患者血液标本的XRCC1 Arg194Trp、Arg399Gln SNP的基因型频率分布,分析其与宫颈癌放疗敏感性的关系。结果 XRCC1基因Arg194Trp分型中,携带Arg/Arg、Arg/Trp、TrP/Trp分别有31例(42.5%)、37例(50.7%)、5例(6.8%);Arg399Gln分型中,携带Arg/Arg、Arg/Gln、Gln/Gln分别有26例(35.6%)、39例(53.4%)、8例(11.0%)。CR组与PR组Arg194Trp、Arg399Gln基因型分布差异均无统计学意义。影响放疗敏感性的多因素Logistic回归分析结果显示,临床分期晚为PR的危险因素。结论 XRCC1基因Arg194TrpSNP、Arg399Gln SNP与外生型宫颈鳞状细胞癌放疗敏感性无相关性。临床分期越晚放疗敏感性越差。展开更多
目的探讨原发性肝癌组织和正常肝脏组织的DNA损伤修复基因XRCC1启动子甲基化状态,分析其与肝癌易感性的关系及对患者预后的影响。方法甲基化特异性PCR检测手术切除的肝癌组织78例及正常肝组织78例的XRCC1基因甲基化情况,并随访3年以上...目的探讨原发性肝癌组织和正常肝脏组织的DNA损伤修复基因XRCC1启动子甲基化状态,分析其与肝癌易感性的关系及对患者预后的影响。方法甲基化特异性PCR检测手术切除的肝癌组织78例及正常肝组织78例的XRCC1基因甲基化情况,并随访3年以上。结果肝癌组的XRCC1启动子甲基化率远高于对照组(P<0.05),肝癌组发生XRCC1启动子甲基化的危险是对照组的13倍(4.089 vs 41.332);XRCC1启动子甲基化的个体发生肝癌的危险是非甲基化的10.36倍(3.423 vs 31.354)(P<0.05);XRCC1启动子甲基化可致肝癌患者无进展期生存率和总体生存率降低(P<0.05)。结论 DNA损伤修复基因XRCC1启动子甲基化在肝癌发生和发展的过程中起着重要作用,并对肝癌患者较差的预后具有提示作用。展开更多
Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glu...Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glucuronosyltransferase(UGT1A7), an important phase II biotransformation enzyme, and X-ray repair cross-complementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China. Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77). Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.展开更多
BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. ...BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE: To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi'an Jiaotong University from June 2007 to September 2008. MATERIALS: SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK (Thr183/Tyr185) polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 (XRCC1) and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS: A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group (I/R group) were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group (pre-SP group) was given 10 μL SP600125 (3 μg/μL). Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS: Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased (P 〈 0.01). Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased (P 〈 0.01). Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased (P 〈 0.05) following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group (P 〈 0.05). Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region (r = -0.983, -0.953, P 〈 0.01). CONCLUSION: SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.展开更多
Objective:To assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.Methods:We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and the...Objective:To assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.Methods:We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.Results:Four studies with 1343 cases and 2302 controls were included.Our analysis found:at codon 194,the Trp allele did not decrease pancreatic cancer risk (Arg/Arg versus Trp/Trp:OR=0.97;95% CI:0.48-1.96;P=0.97;Arg/Arg versus Arg/Trp:OR=0.89;95% CI:0.70-1.13;P=0.55;Arg/Trp versus Trp/Trp:OR=1.06;95% CI:0.52-2.16;P=0.90);at codon 280,only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk;at codon 399,the Gln allele also showed no signi?cant effect on pancreatic cancer compared to Arg allele (Arg/Arg versus Gln/Gln:OR=0.94;95% CI:0.74-1.18;Arg/Arg versus Arg/Gln:OR=0.97;95% CI:0.83-1.13;Arg/Gln versus Gln/Gln:OR=0.97;95% CI:0.77-1.22).The shape of the funnel plot and the Egger's test did not detect any publication bias.Conclusion:There is no evidence that XRCC1 polymorphisms (Arg194Trp,Arg280His,and Arg399Gln) are associated with pancreatic cancer risk.展开更多
The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%-30% smokers dev...The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC 1), a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16=0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.展开更多
To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first...To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.展开更多
Background Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, only 20%-30% of smokers...Background Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, only 20%-30% of smokers develop COPD, suggesting that different degrees of DNA repair produce different outcomes in smokers, i.e., part of them develop COPD. We investigated the association between polymorphisms in DNA repair genes hOGG1 (Ser326Cys) and XRCC1 (Arg399GIn), alone or in combination, and susceptibility of COPD. Methods Altogether 201 COPD patients and 309 controls were recruited and frequency-matched on age and sex. hOGG1 and XRCC1 genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The risk of COPD was not significantly different among individuals with Ser/Cys and Cys/Cys genotypes compared with those with hOGG1 Ser/Ser genotype. The risk of COPD was not significantly different among individuals with Gin/Gin genotype compared with those with XRCC1 Arg/Arg genotype, but it was significantly elevated among individuals with Arg/GIn genotype (adjusted odds ratios (OR)=1.55, 95% confidence intervals (CI) 1.05-2.29, P=0.029). Assessment of smoking status in current smokers compared with those with hOGG1 Ser/Ser genotype revealed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR=5.07, 95% CI 1.84-13.95, P=0.002). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/GIn genotype (adjusted OR=2.77, 95% CI 1.52-5.07, P=-0.001). Assessment of smoking exposure in light smokers compared with those with hOGG1 Ser/Ser genotype showed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR=4.02, 95% CI 1.05-16.80, P=0.042). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Gin/Gin genotype (adjusted OR=4.48, 95% CI 1.35-14.90, P=0.014). In heavy smokers compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/GIn genotype (adjusted OR= 2.55, 95% CI 1.42-4.58, P=0.002). When hOGG1 Ser326Cys and XRCC1 Arg399GIn polymorphisms were evaluated together, compared with those with 0-1 of hOGG1 326Cys and XRCC1 399Gin alleles, the risk of COPD was significantly elevated among individuals with 3-4 of hOGG1 326Cys and XRCC1 399Gin alleles (adjusted OR=3.18, 95% CI 1.86-5.43, P=0.000). Assessment of smoking status and smoking exposure in current/light/heavy smokers showed that the risk of COPD was significantly elevated among individuals with 3-4 of hOGG1 326Cys and XRCC1 399Gin alleles (adjusted OR=8.32, 95% CI 3.59-19.27, P=0.000; OR=5.46, 95% CI 2.06-14.42, P=0.001; OR=2.93, 95% CI 1.43-6.02, P=0.003; respectively). Conclusions hOGG1 Ser326Cys and XRCC1 Arg399GIn polymorphisms are associated with the susceptibility to COPD. The risk of COPD is significantly elevated among current/light smokers with hOGG1 326Cys and XRCC1 399Gin.展开更多
基金Supported by International Science and Technology Cooperation Program of the Ministry of Science and Technology,No.010S2012ZR0058the National Basic Research Program of China,No. 2012CB526706+2 种基金the Innovation Program of Shanghai Municipal Education Commission,No.13ZZ060the Fund of Shanghai Municipal Health Bureau,No. 2008Y077the Special Program for Military Medicine,No. 2010JS15
文摘AIM: To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS: Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg's and Egger's tests did not find any obvious publication bias. CONCLUSION: The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.
基金supported by the National Natural Science Foundation of China(No.81100274,81001428)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Objective: The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCCI) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods: Immunohistochemistry (IHC) was used to evaluate XRCCI protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Among 612 patients staged II/III in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P=0.347) or DFS (P=0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P=0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P=0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P〈0.05). Though XRCCI plays an important role in DNA repair pathways, no significant relationship is found in XRCCI expression and OS among gastric cancer in our study. Conclusions: XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.
基金supported by the National Natural Science Foundation of China, No. 30571790
文摘Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.
文摘Objective: To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 (XRCC1) and the susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods: Relevant case-control studies were enrolled in the meta-analysis. We applied Rev Man 4.2 software to pool raw data and test studies' heterogeneity and to calculate the incorporated odds ratio (OR) and 95% confidence interval (95% CI). Results: Our data showed that the OR for the Gln allele of the Arg399Gln polymorphism, compared with the Arg allele, was 1.35 (95% CI, 1.16-1.57; P〈0.0001) for childhood ALL patients. Similarly, the homozygous genotype Gln/Gln and heterozygous genotype Arg/Gln both significantly increased the risk of childhood ALL compared with the wild genotype Arg/Arg (OR =1.58; 95% CI, 1.13-2.21; P=0.008; OR =1.51; 95% CI, 1.21-1.87; P=0.0002). The dominant model of Arg399Gln was associated with childhood ALL risk (OR =1.54; 95% CI, 1.25-1.89; P〈0.0001). The ethnic subgroup analysis demonstrated that the Gln allele in all five ethnic groups was prone to be a risk factor for childhood ALL just with different degrees of correlation while Arg194Trp SNP showed a protective or risk factor or irrelevant thing in different races. Conclusions: XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.
基金The Fundamental Research Funds for Jilin University in China,No.450060445246the High-Tech Industrial Development Project of Jilin Province in China,No.20090633+1 种基金the Scientific Research Foundation of Jilin Province in China,No.20130206001YY,20120713 and 200905169the Scientific Research Foundation of Changchun in China,No.12SF29
文摘OBJECTIVE: To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399GIn, Arg194Trp and Arg280His polymorphisms with the risk of glioma. DATA SOURCES: A systematic literature search of papers published from January 2000 to August 2012 in PubMed, Embase, China National Knowledge Infrastructure database, and Wanfang da- tabase was performed. The key words used were "glioma", "polymorphism", and "XRCC1 or X-ray repair cross-complementing group 1". References cited in the retrieved articles were screened manually to identify additional eligible studies. STUDY SELECTION: Studies were identified according to the following inclusion criteria: case-control design was based on unrelated individuals; and genotype frequency was available to estimate an odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed for the selected studies after strict screening. Dominant and recessive genetic models were used and the relationship between homozygous mutant genotype frequencies and mutant gene frequency and glioma incidence was investigated. We chose the fixed or random effect model according to the heterogeneity to calculate OR and 95%CI, and sensitivity analyses were conducted. Publication bias was examined using the inverted funnel plot and the Egger's test using Stata 12.0 software. MAIN OUTCOME MEASURES: Association of XRCC1 Arg399GIn, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to differ- ent ethnicities of the subjects.RESULTS: Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399GIn polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gin/Gin + GIn/Arg versus Arg/Arg: OR = 1.26, 95%CI= 1.03-1.54, P = 0.02). In the subgroup analysis by ethnicity, significantly increased risk was found in Asian subjects in the recessive (OR = 1.46, 95%CI= 1.04-2.45, P = 0.03) and dominant models (OR = 1.40, 95%CI= 1.10-1.78, P = 0.007), and homozygote contrast (OR = 1.69, 95%CI= 1.17-2.45, P = 0.005), but not in Caucasian sub- jects. For association of the Arg194Trp (eight studies) and Arg280His (four studies) polymorphisms with glioma risk, the meta-analysis did not reveal a significant effect in the allele contrast, the recessive genetic model, the dominant genetic model, or homozygote contrast. CONCLUSION: The XRCC1 Arg399GIn polymorphism may be a biomarker of glioma susceptibility, espe- cially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.
文摘AIM: To evaluate the association between X-ray crosscomplementing gene 1 (XRCCl) genetic polymorphism Arg399Gln and gastric cancer risk by means of metaanalysis. METHODS: We searched PubMed and NCBI up to June 1, 2008. A total of 16 clinical trials and reports were identified, but only 8 trials qualified under our selection criteria. Statistical analysis was performed with the software program Review Manage, version 4.2.8. RESULTS: Of the 8 case-control studies selected for this meta-analysis, a total of 1334 gastric cancer cases and 2194 controls were included. For Arg399GIn, the Gin/Gin genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR = 0.92, 95% CI, 0.71-1.19; P = 0.51). Similarly, no associations were found in the recessive and dominant modeling (Gin/Gin vs Arg/GIn + Arg/Arg: OR = 0.96; 95% CI, 0.77-1.19; P = 0.70 and Gin/Gin + Arg/GIn vs Arg/Arg: OR = 0.90, 95% CI, 0.77-1.05; P = 0.18). CONCLUSION: No association is found between the XRCC1 polymorphism Arg399GIn and gastric cancer risk.
文摘目的探讨原发性肝癌组织和正常肝脏组织的DNA损伤修复基因XRCC1启动子甲基化状态,分析其与肝癌易感性的关系及对患者预后的影响。方法甲基化特异性PCR检测手术切除的肝癌组织78例及正常肝组织78例的XRCC1基因甲基化情况,并随访3年以上。结果肝癌组的XRCC1启动子甲基化率远高于对照组(P<0.05),肝癌组发生XRCC1启动子甲基化的危险是对照组的13倍(4.089 vs 41.332);XRCC1启动子甲基化的个体发生肝癌的危险是非甲基化的10.36倍(3.423 vs 31.354)(P<0.05);XRCC1启动子甲基化可致肝癌患者无进展期生存率和总体生存率降低(P<0.05)。结论 DNA损伤修复基因XRCC1启动子甲基化在肝癌发生和发展的过程中起着重要作用,并对肝癌患者较差的预后具有提示作用。
基金supported by the grant from Department of Education of Liaoning Province, China (No. 2008S232)
文摘Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glucuronosyltransferase(UGT1A7), an important phase II biotransformation enzyme, and X-ray repair cross-complementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China. Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77). Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.
基金Supported by: the National Natural Science Foundation of China, No. 30571790
文摘BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE: To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi'an Jiaotong University from June 2007 to September 2008. MATERIALS: SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK (Thr183/Tyr185) polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 (XRCC1) and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS: A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group (I/R group) were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group (pre-SP group) was given 10 μL SP600125 (3 μg/μL). Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS: Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased (P 〈 0.01). Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased (P 〈 0.01). Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased (P 〈 0.05) following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group (P 〈 0.05). Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region (r = -0.983, -0.953, P 〈 0.01). CONCLUSION: SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.
文摘Objective:To assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.Methods:We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.Results:Four studies with 1343 cases and 2302 controls were included.Our analysis found:at codon 194,the Trp allele did not decrease pancreatic cancer risk (Arg/Arg versus Trp/Trp:OR=0.97;95% CI:0.48-1.96;P=0.97;Arg/Arg versus Arg/Trp:OR=0.89;95% CI:0.70-1.13;P=0.55;Arg/Trp versus Trp/Trp:OR=1.06;95% CI:0.52-2.16;P=0.90);at codon 280,only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk;at codon 399,the Gln allele also showed no signi?cant effect on pancreatic cancer compared to Arg allele (Arg/Arg versus Gln/Gln:OR=0.94;95% CI:0.74-1.18;Arg/Arg versus Arg/Gln:OR=0.97;95% CI:0.83-1.13;Arg/Gln versus Gln/Gln:OR=0.97;95% CI:0.77-1.22).The shape of the funnel plot and the Egger's test did not detect any publication bias.Conclusion:There is no evidence that XRCC1 polymorphisms (Arg194Trp,Arg280His,and Arg399Gln) are associated with pancreatic cancer risk.
基金supported by a grant from National Natural Science Foundation of China (No.30570794)
文摘The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC 1), a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16=0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.
文摘To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30570794).
文摘Background Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, only 20%-30% of smokers develop COPD, suggesting that different degrees of DNA repair produce different outcomes in smokers, i.e., part of them develop COPD. We investigated the association between polymorphisms in DNA repair genes hOGG1 (Ser326Cys) and XRCC1 (Arg399GIn), alone or in combination, and susceptibility of COPD. Methods Altogether 201 COPD patients and 309 controls were recruited and frequency-matched on age and sex. hOGG1 and XRCC1 genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The risk of COPD was not significantly different among individuals with Ser/Cys and Cys/Cys genotypes compared with those with hOGG1 Ser/Ser genotype. The risk of COPD was not significantly different among individuals with Gin/Gin genotype compared with those with XRCC1 Arg/Arg genotype, but it was significantly elevated among individuals with Arg/GIn genotype (adjusted odds ratios (OR)=1.55, 95% confidence intervals (CI) 1.05-2.29, P=0.029). Assessment of smoking status in current smokers compared with those with hOGG1 Ser/Ser genotype revealed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR=5.07, 95% CI 1.84-13.95, P=0.002). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/GIn genotype (adjusted OR=2.77, 95% CI 1.52-5.07, P=-0.001). Assessment of smoking exposure in light smokers compared with those with hOGG1 Ser/Ser genotype showed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype (adjusted OR=4.02, 95% CI 1.05-16.80, P=0.042). Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Gin/Gin genotype (adjusted OR=4.48, 95% CI 1.35-14.90, P=0.014). In heavy smokers compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/GIn genotype (adjusted OR= 2.55, 95% CI 1.42-4.58, P=0.002). When hOGG1 Ser326Cys and XRCC1 Arg399GIn polymorphisms were evaluated together, compared with those with 0-1 of hOGG1 326Cys and XRCC1 399Gin alleles, the risk of COPD was significantly elevated among individuals with 3-4 of hOGG1 326Cys and XRCC1 399Gin alleles (adjusted OR=3.18, 95% CI 1.86-5.43, P=0.000). Assessment of smoking status and smoking exposure in current/light/heavy smokers showed that the risk of COPD was significantly elevated among individuals with 3-4 of hOGG1 326Cys and XRCC1 399Gin alleles (adjusted OR=8.32, 95% CI 3.59-19.27, P=0.000; OR=5.46, 95% CI 2.06-14.42, P=0.001; OR=2.93, 95% CI 1.43-6.02, P=0.003; respectively). Conclusions hOGG1 Ser326Cys and XRCC1 Arg399GIn polymorphisms are associated with the susceptibility to COPD. The risk of COPD is significantly elevated among current/light smokers with hOGG1 326Cys and XRCC1 399Gin.