X-ray Repair Cross-complementing Gene Research Articles

X-ray Repair Cross Complementing 1 (XRCC1) Gene Polymorphism in Hepatocellular Carcinoma (HCC)

Abstract Background Several risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. The human X-ray repair cross- complementing protein 1 (XRCC1) gene encodes for one of the major repair factors involved in base excision repair (BER), which is reported to be associated with the risk of several cancers. A few studies have explored the association between risk of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in different DNA repair genes. Aim of the Work to investigate the possible association between XRCC1-G28152A (rs25487) single nucleotide polymorphism (SNP) and hepatocellular carcinoma (HCC) in chronic hepatitis C patients. Patients and Methods The study included 35 patients who had HCC and 15 patients who had liver cirrhosis. XRCC1 gene polymorphism was done to all participants by RT-PCR After collection of relevant clinical data and basic laboratory tests. Results A statistically higher frequency of XRCC1 (GG, GA) genotypes and increased (G) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group but Our results revealed that the genotypic and allelic frequencies of XRCC1 gene polymorphism rs25487 didn’t show statistically significant difference between HCC patients group and liver cirrhosis control group. Conclusion The present study had demonstrated that there was no significant association between XRCC1 gene polymorphism (rs25487) and HCC in the sample of Egyptian population included in our study. Also, non-significant differences among the XRCC1 genotypes and alleles were found regarding age, sex, BMI and laboratory data including CBC, AFP, coagulation profile (PT, INR), liver function test ( total protein, albumin, AST, total bilirubin and direct bilirubin), BCLC and Milan criteria. While a statistically significant difference was observed as regards PTT and ALT between genotypes.

The influence of XRCC1 gene polymorphism on the prognosis and safety of stage Ⅲ patients with colorectal cancer who received oxaliplatin based adjuvant chemotherapy

Objective: To investigate the influence of X-ray repair cross complementing 1 (XRCC1) gene polymorphism on the prognosis and safety of stage Ⅲ patients with colorectal cancer (CRC) who received oxaliplatin based adjuvant chemotherapy. Methods: A total of 218 stage Ⅲ patients with CRC after R0 resection and received oxaliplatin based adjuvant chemotherapy in the department of gastrointestinal surgery of the First Affiliated Hospital of Zhengzhou University from March 2012 to December 2019 were included and the baseline characteristics were collected. There were 125 male and 93 female patients, aged from 18 to 78 years. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimens of the colorectal cancer patients were preserved for genotyping of XRCC1 gene genetic variation and mRNA expression of XRCC1, respectively. The association between genotype status and prognosis was analyzed by Kaplan-Meier survival analysis. And the correlation between genotype status and adverse reactions was performed with χ2 test. Results: The median follow-up time were 4.9 (0.3-7.3) years. The median disease-free survival (DFS) of the 218 patients with CRC was 4.4 years and the median overall survival (OS) was 5.5 years. The prevalence of rs1799782 in XRCC1 gene among the 218 patients was: GG genotype 62.4% (136/218), GA genotype 33.0% (72/218) and AA genotype 4.6% (10/218), minor allele frequency was 0.21. And the distribution frequencies of the three genotypes were in accordance with the hardy-weinberg equilibrium (P=0.905). GA and AA genotypes were merged in the subsequent analysis. The median DFS [M (95%CI)] of GG genotype and GA/AA genotype was 5.2 (4.5-5.9) years and 3.8 (3.2-4.4) years, which was statistically significant (χ²=6.943, P=0.008). Furthermore, the median OS [M (95%CI)] of the two genotypes were 6.0 (5.3-6.7) years and 4.5 (3.9-5.1) years, which was statistically significant (χ²=5.538, P=0.010). The mRNA expression of XRCC1 in PBMC of the patients with GA/AA genotypes was 3.8±0.6,which was significantly higher than that of the GG genotype patients(2.8±0.7) (t=6.140, P<0.001). Conclusion: The prognosis of patients with CRC who received oxaliplatin based adjuvant chemotherapy may be influenced by XRCC1 rs1799782 through mediating the mRNA expression of XRCC1.

Gene expression and prognosis of x-ray repair cross-complementing family members in non-small cell lung cancer

ABSTRACT The X-ray repair cross-complementing gene (XRCC) family participates in DNA damage repair and its dysregulation is associated with the development and progression of a variety of cancers. However, XRCCs have not been systematically studied in non-small cell lung cancer (NSCLC). Using The Cancer Genome Atlas (TCGA) and Oncomine databases, we compared the expression levels of XRCCs between NSCLC and normal tissues and performed survival analysis using the data from TCGA. The correlations of XRCCs with the clinical parameters were then analyzed using UCSC Xena. Genetic alterations in XRCCs in NSCLC and their effects on the prognosis of patients were presented using cBioPortal. SurvivalMeth was used to explore the differentially methylated sites associated with NSCLC and their effect on prognosis. Next, the immunological correlations of XRCCs expression level were analyzed using TIMER 2.0. Finally, GeneMANIA was used to visualize and analyze the functionally relevant genes, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional and pathway enrichment analyses of prognostic genes. Our results revealed that XRCCs were overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Univariate and multivariate Cox analyses showed that XRCC4/5/6 were independent risk factors for LUAD. Additionally, genetic alterations, methylation, and immune cell infiltration demonstrated an association between XRCC4/5/6 and poor prognosis in LUAD. Finally, the KEGG-enriched and non-homologous end-joining (NHEJ) pathways were shown to be associated with XRCC4/5/6. In conclusion, our study demonstrated that XRCC4/5/6 could be used as diagnostic and prognostic biomarkers for LUAD.

Effects of DNA Damage and Oxidative Stress in Human Bronchial Epithelial Cells Exposed to PM2.5 from Beijing, China, in Winter.

Epidemiological studies have corroborated that respiratory diseases, including lung cancer, are related to fine particulate matter (<2.5 μm) (PM2.5) exposure. The toxic responses of PM2.5 are greatly influenced by the source of PM2.5. However, the effects of PM2.5 from Beijing on bronchial genotoxicity are scarce. In the present study, PM2.5 from Beijing was sampled and applied in vitro to investigate its genotoxicity and the mechanisms behind it. Human bronchial epithelial cells 16HBE were used as a model for exposure. Low (67.5 μg/mL), medium (116.9 μg/mL), and high (202.5 μg/mL) doses of PM2.5 were used for cell exposure. After PM2.5 exposure, cell viability, oxidative stress markers, DNA (deoxyribonucleic acid) strand breaks, 8-OH-dG levels, micronuclei formation, and DNA repair gene expression were measured. The results showed that PM2.5 significantly induced cytotoxicity in 16HBE. Moreover, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cellular heme oxygenase (HO-1) were increased, and the level of glutathione (GSH) was decreased, which represented the occurrence of severe oxidative stress in 16HBE. The micronucleus rate was elevated, and DNA damage occurred as indicators of the comet assay, γ-H2AX and 8-OH-dG, were markedly enhanced by PM2.5, accompanied by the influence of 8-oxoguanine DNA glycosylase (OGG1), X-ray repair cross-complementing gene 1 (XRCC1), and poly (ADP-ribose) polymerase-1 (PARP1) expression. These results support the significant role of PM2.5 genotoxicity in 16HBE cells, which may occur through the combined effect on oxidative stress and the influence of DNA repair genes.

Evaluation of X-Ray Repair Cross-Complementing Family Members as Potential Biomarkers for Predicting Progression and Prognosis in Hepatocellular Carcinoma.

The X-ray repair cross-complementing (XRCC) gene family has been revealed to participate in the carcinogenesis and development of numerous cancers. However, the expression profiles and prognostic values of XRCCs (XRCC1-6) in hepatocellular carcinoma (HCC) have not been explored up to now. The transcriptional levels of XRCCs in primary HCC tissues were analyzed by UALCAN and GEPIA. The relationship between XRCCs expression and HCC clinical characteristics was evaluated using UALCAN. Moreover, the prognostic values of XRCCs expression and mutations in HCC patients were investigated via the GEPIA and cBioPortal, respectively. Last but not least, the functions and pathways of XRCCs in HCC were also predicted by cBioPortal and DVAID. The transcriptional levels of all XRCCs in HCC tissues were notably elevated compared with normal liver tissues. Meanwhile, upregulated XRCCs expression was positively associated with clinical stages and tumor grades of HCC patients. Survival analysis using the GEPIA database revealed that high transcription levels of XRCC2/3/4/5/6 were associated with lower overall survival (OS) and high transcription levels of XRCC1/2/3/6 were correlated with poor disease-free survival (DFS) in HCC patients. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated the possible mechanisms of XRCCs and their associated genes participating in the oncogenesis of HCC. Our findings systematically elucidate the expression profiles and distinct prognostic values of XRCCs in HCC, which might provide promising therapeutic targets and novel prognostic biomarkers for HCC patients.

Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk.

AimThe X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high.MethodsThe present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene–gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression.ResultsFor XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3–0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26–0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27–0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0–2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r2=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk.ConclusionXRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.

New sights on the associations between the XRCC1 gene polymorphisms and hepatocellular carcinoma susceptibility.

Studies investigating the relationships between the polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene and the susceptibility of hepatocellular carcinoma (HCC) remained controversial, therefore, we assessed this associations by metaanalysis and trial sequential analysis (TSA). PubMed, Embase, Google Scholar, Chinese National Knowledge Infrastructure and Baidu Scholar were comprehensively screened to retrieve relevant studies up to May 20, 2019. A total of 32 studies was included. Significant associations were discovered in the overall and subgroup analysis in these three polymorphisms. Interestingly, the decreased risk of HCC was detected in the Indians for the rs24587 polymorphism. TSA indicated the required information size for the rs25487 polymorphism were reached, but for the rs25489 and rs1799782 polymorphisms, more well-designed trials were required. Sensitivity analysis implied our results were stable; no publication bias was observed in the rs25487 and rs1799782 polymorphisms. The bioinformatic analysis indicate that the rs1799782 polymorphism is probably damaging and has an influence on the XRCC1 protein function. Our study indicated that the XRCC1 rs25487 was a risk factor for the susceptibility of HCC, which was verified by the TSA. In addition, the rs25489 and rs1799782 polymorphisms were associated with increased risk of HCC. In the subgroup analysis, increased risks were detected in some subgroups (in accordance with Hardy-Weinberg equilibrium, Chinese groups, Mongoloid subgroup, polymerase chain reaction-restriction fragment length polymorphisms and more than 300 subgroups), moreover, decreased HCC risk of the rs25487 polymorphism was firstly observed, which required further studies to verify.

XRCC2 promotes cancer progression by regulating p53/p21 signaling pathway in hepatocellular carcinoma

Introduction: X-ray repair cross-complementing gene 2 (XRCC2) plays an important role in DNA damage repair. However, how the expression of XRCC2 was regulated in the progression of hepatocellular carcinoma(HCC) remains unknown. The aim of this study is to investigated the expression of XRCC2 in HCC and to unravel the underlying mechanism of XRCC2 in HCC. Method: The expression of XRCC2 in tissues from HCC patients was analyzed using a microarray and real-time PCR. The effects of XRCC2 on cell proliferation and tumorigenesis in HCC cells were analyzed by flow cytometry, colony formation assays and CCK8 assays. The correlation between XRCC2 expression and long-term outcomes after liver resection, as well as the potential molecular mechanism of XRCC2 in regulating the proliferation in HCC cells were also addressed. Result: The expression of XRCC2 was higher in tumor tissues and HCC cell lines compared to the adjacent liver tissues and normal liver cell lines. The expression level of XRCC2 has a reverse relationship with the long-term outcomes after liver resection. Down-regulating the expression of XRCC2 in HCC cell strains could inhibit the proliferation of HCC cells by inducing S-phase arrest and cell apoptosis in vitro and in vivo. Further study indicates that down-regulating the expression of XRCC2 could induce the up-regulation of p53/p21 signaling pathway. Conclusion: This study provides novel insights into the role of XRCC2 in controlling HCC cell proliferation and tumorigenesis, and identifies XRCC2 as a potential prognostic marker and therapeutic target.

Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy

We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT). In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged≥18years, had stage III to IVB disease, had a Karnofsky Performance Status≥80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria.Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P=.023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P=.003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P=.006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P=.209). At a median follow-up of 21months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P=.077) and 73.0% versus 55.5% (P=.143), respectively. Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant.

Association between XRCC1 single-nucleotide polymorphism and acute radiation reaction in patients with nasopharyngeal carcinoma: A cohort study.

To explore the association of the X-ray repair cross-complementing gene 1 (XRCC1) codon 399 single-nucleotide polymorphism (SNP) with acute radiation dermatitis and oral mucositis in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiation therapy (IMRT).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the SNP of the XRCC1 codon 399 in 114 NPC patients before radiotherapy.The risk of patients with the Arg/Arg genotype suffering from acute radiation dermatitis Grade ≥2 was higher than the other 2 genotypes (P = .014, 95% CI: 1.182–4.582). No significant difference was observed in the degree of acute radiation oral mucositis injury among the patients with different genotypes (P = .449, 95% CI: 0.691–2.304). Multivariate analysis showed that N stage and genotype were significantly associated with acute radiation dermatitis of Grade ≥2 (OR = 3.221, P < .001, 95% CI: 1.669–6.216, OR = 2.860, P = .006, 95% CI: 1.354–6.043). T stage and smoking status were significantly associated with acute radiation oral mucositis with Grade ≥2 (OR = 2.508, P = .001, 95% CI: 1.427–4.408, OR = 6.355, P < .001, 95% CI: 2.533–15.841).The XRCC1 codon 399 genotype in NPC could be an important predicting factor in the risk of acute radiation dermatitis during IMRT.

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma.

The objectives of this study were to evaluate the impact of two X-ray repair cross complementing 1 (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) on the risk of development of colorectal cancer (CRC) and to assess the expression levels of microRNA-21 (miR-21) in CRC patients. A case-control cross sectional study was conducted on 50 CRC patients and 50 cancer-free subjects. DNA and miR-21 were extracted from whole blood samples. The expression levels of the XRCC1 polymorphisms and miR-21 were assessed by real-time PCR in all subjects of the study. Genotype analysis revealed a significant association between CRC risk and both the Arg194Trp genotype (OR=11.407, 95% CI=4.039-32.221, p<0.001) and the Arg399Gln genotype (OR=3.778, 95% CI= 1.6-8.919, p=0.002). The expression levels of circulating miR-21 were able to detect CRC cases significantly (p=0.022) with a sensitivity of 82% and a specificity of 56% (Area under the curve (AUC)=0.633) but were unable to distinguish between early and late cases (AJCC classification) (p=0.194). The XRCC1 Arg194Trp and Arg399Gln polymorphisms both confer high susceptibility for the development of CRC. Circulating miR-21 expression levels are a potentially diagnostic non-invasive genetic marker of CRC.

Common polymorphisms of thehOGG1, APE1andXRCC1genes correlate with the susceptibility and clinicopathological features of primary angle-closure glaucoma

The present case study aims to elucidate the correlation between the human 8-hydroxyguanineglycosylase (hOGG1), APE1 and X-ray repair cross-complementing gene 1 (XRCC1) gene polymorphisms to the susceptibility and clinicopathological features of primary angle closure glaucoma (PACG) in a Chinese Han population. Blood samples were obtained from 258 PACG patients (case group) and 272 healthy volunteers (control group). PCR with sequence-specific primer (PCR-SSP) was used to determine the allele frequencies and genotype distributions of the hOGG1, APE1 and XRCC1 genes. The risk factors of PACG were determined using logistic regression analysis. The results indicated that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were correlated with the risk of PACG. Furthermore, there were thicker corneas, higher intraocular pressure (IOP) and a shorter axial length in patients carrying the mutant genotypes of hOGG1 Ser326Cys (Ser/Cys + Cys/Cys), APE1 Asp148Glu (Asp/Glu + Glu/Glu) and XRCC1 Arg399Gln (Arg/Gln + Glu/Glu) than those carrying the corresponding wild-type genotypes. According to the logistic regression analysis, Asp148Glu and Arg399Gln polymorphisms, a short axial length and high IOP are major risk factors for PACG. These findings reveal that hOGG1 Ser326Cys, APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms are correlated with the risk and clinicopathological features of PACG in a Chinese Han population.

Association of XRCC1 gene polymorphism and low dose ionizing radiation with peripheral blood lymphocyte micronucleus

Objective: To explore the effects of X-ray repair cross complementing gene 1 (XRCC1) polymorphism and low dose ionizing radiation exposure on radiology professionals' peripheral blood lymphocyte micronucleus. Methods: A matched case-control study was designed. From 2013 to 2015, 1 102 radiology professionals with micronucleus test rusults, and 45 cases with present micronucleus were enroled into case group. 180 diagnostic radiology technicians detecting no micronucleus were chosen as control group, cases and controls were 1∶4 mached on gender, age ≤40 or >40 years old. According to the detection of micronucleus levels (0‰, 1‰, 2‰) , the objects of our study were divided into the reference group, the low detection group and the medium detection group. The form of radiation workers' occupational health examination was used to collect the general baseline of the research objects, history of smoking, drinking, poisonous and harmful material exposure, past medical history, accumulated illuminated dose and lymphocyte micronucleus rates (‰) , etc. Using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) technology for genotyping; Compared the baseline data and radiation exposure level between the differentmicrokernel detection groups; Adopted multivariate logistic regression to analysis the combination effect of XRCC1 Arg399Gln gene polymorphism and accumulated illuminated dosefor micronucleus rate. Results: The accumulated illuminated dose in the reference group, the low detection group and the medium detection group were (23.44±15.23) , (21.76±2.56) , (24.22±18.61) mSv, respectively. There was no statistically significant difference among the groups (P>0.05) . Under the dominant inheritance mode, after adjusted age, smoking and drinking factors, the results suggested that XRCC1 Arg399Gln micronucleus medium detection group compared with the reference group, Arg399Gln-GG as reference, Arg399Gln-GA+AA decreased the occurrence of micronucleus (OR=0.175, 95%CI: 0.036-0.848) . Arg194Trp and Arg280His did not affect the incidence of micronucleus (P>0.05) . Did not find the combination effect of XRCC1 Arg399Gln gene polymorphism and accumulated illuminated dose for micronucleus rate (P>0.05) . Conclusion:XRCC1 Arg399Gln gene polymorphism can affect the incidence of micronucleus, and carrying the XRCC1 Arg399Gln-GA+AA genotype is a protective factor of micronucleus's occurrence, but low dose ionizing radiation may not affect the occurrence of micronucleus independently.

Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta-Analysis.

Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13–1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12–1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03–1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19–2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06–1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

Association of XRCC1 Arg399Gln and Arg194Trp polymorphisms with susceptibility to multiple autoimmune diseases: a meta-analysis.

The role of the X-ray repair cross-complementing gene 1(XRCC1) Arg399Gln and Arg194Trp polymorphisms has been involved in the investigations of susceptibility to multiple autoimmune diseases, but the results were inconsistent. Here, we have performed a meta-analysis to clarify the relationship between them. All appropriate case-control studies were searched in the PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) database. A meta-analysis was conducted on the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of autoimmune diseases. Pooled odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. Fourteen relevant studies with a total of 2886 cases and 3257 controls were analyzed in our research. Analysis for the XRCC1 Arg399Gln polymorphism under recessive model (OR 1.53, 95% CI 1.07-2.18, P=0.019), dominant model (OR 1.36, 95% CI 1.04-1.77, P=0.026) and homozygous model (OR 1.67, 95% CI 1.07-2.62, P=0.024) indicated an association in the overall population, as well as in Caucasian populations under the recessive model (OR 1.73, 95% CI 1.03-2.91, P=0.039) and Asian populations under dominant model (OR 1.31, 95% CI 1.02-1.70, P=0.037). Stratification by disease indicated significant association between XRCC1 Arg399Gln and rheumatoid arthritis (RA) in all genetic models (P<0.05). However, there was no significant association between XRCC1 Arg194Trp polymorphism and autoimmune diseases in different genetic models. The current meta-analysis demonstrates that the XRCC1 Arg399Gln polymorphism confers susceptibility to autoimmune diseases in Asians and Caucasians and, in particular, shows that XRCC1 Arg399Gln polymorphism is associated with RA.

Identification of biomarkers for pseudo and true progression of GBM based on radiogenomics study.

The diagnosis for pseudoprogression (PsP) and true tumor progression (TTP) of GBM is a challenging task in clinical practices. The purpose of this study is to identify potential genetic biomarkers associated with PsP and TTP based on the clinical records, longitudinal imaging features, and genomics data. We are the first to introduce the radiogenomics approach to identify candidate genes for PsP and TTP of GBM. Specifically, a novel longitudinal sparse regression model was developed to construct the relationship between gene expression and imaging features. The imaging features were extracted from tumors along the longitudinal MRI and provided diagnostic information of PsP and TTP. The 33 candidate genes were selected based on their association with the imaging features, reflecting their relation with the development of PsP and TTP. We then conducted biological relevance analysis for 33 candidate genes to identify the potential biomarkers, i.e., Interferon regulatory factor (IRF9) and X-ray repair cross-complementing gene (XRCC1), which were involved in the cancer suppression and prevention, respectively. The IRF9 and XRCC1 were further independently validated in the TCGA data. Our results provided the first substantial evidence that IRF9 and XRCC1 can serve as the potential biomarkers for the development of PsP and TTP.

Association between XRCC1 polymorphisms and chromosome damage in workers exposed to benzene in jewelcrafting industry

To investigate the association between the gene polymorphisms of the DNA damage repair gene X-ray repair cross-complementing gene 1 (XRCC1) and susceptibility to chromosome damage in workers exposed to low-concentration benzene in the jewelcrafting industry. A total of 286 workers exposed to benzene in jewelcrafting enterprises were enrolled as study subjects from January 2013 to December 2014. Gas chromatography was used to measure benzene concentration in workplace, cytokinesis-block micronucleus test was used to analyze the level of chromosome damage in peripheral blood, and the Sequenom technique was used to determine the single nucleotide polymorphisms of XRCC1. The time-weighted average concentration of benzene in workplace was <0.6~1.8 mg/m(3), lower than the national occupational exposure limit (6 mg/m(3)). The distribution of allele frequencies met the Hardy-Weinberg equilibrium in genetics (P>0.05). Increase in age (RR=1.38, 95%CI 1.06~3.75) and increase in working years (RR=1.45, 95%CI 1.18~2.58) were risk factors for the increase in micronucleus frequency. Compared with those with the wild-type homozygous genotype, the individuals with XRCC1 rs25487 CT genotype showed a significantly higher risk of increase in micronucleus frequency (RR=1.51, 95% CI 1.28~3.87, P<0.05) , and the individuals with XRCC1 rs1799782 AA genotype also showed a significantly higher risk of increase in micronucleus frequency (RR=1.65, 95% CI 1.30~3.12, P<0.05). There was no clear association between XRCC1 rs25489 polymorphisms and micronucleus frequency (P>0.05). Exposure to low-concentration benzene may cause chromosome damage in workers exposed to benzene, and the XRCC1 polymorphisms rs 25487 and rs1799782 may be associated with chromosome damage induced by benzene.

The Arg399Gln polymorphism in the XRCC1 gene is associated with increased risk of hematological malignancies.

The associations between the Arg399Gln polymorphism in X-ray repair cross-complementing gene 1 (XRCC1) gene and the risk of hematological malignancies have been extensively investigated. However, the results were inconsistent. The objective of the current study is to investigate the association by meta-analysis. We searched PubMed database, Embase database, CNKI database, Wanfang database, and Weipu database, covering all studies until August 7, 2013. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. A total of 27 case-control studies concerning the Arg399Gln polymorphism were included from 26 articles. The results suggested that the Arg399Gln polymorphism was not associated with an increased/decreased risk of hematological malignancies in total analysis (OR = 1.15, 95 % confidence interval (CI) = 0.97-1.35, P = 0.10 for Arg/Gln + Gln/Gln vs. Arg/Arg). In the subgroup analysis by ethnicity and cancer types, significant association was found in Asians (OR = 1.35, 95 % CI = 1.04-1.75, P = 0.03) but not in Europeans (OR = 1.07, 95 % CI = 0.86-1.33, P = 0.56), and in leukemia (OR = 1.25, 95 % CI = 1.02-1.54, P = 0.03) but not in lymphoma (OR = 0.98, 95 % CI = 0.80-1.20, P = 0.84) or myeloma (OR = 1.13, 95 % CI = 0.23-5.69, P = 0.88). The current meta-analysis indicated that the Arg399Gln polymorphism in the XRCC1 gene might be a risk factor for hematological malignancies in Asians or for leukemia. In future, more large-scale case-control studies are needed to validate these results.

Polymorphisms of DNA Repair Genes XPD (Lys751Gln) and XRCC1 (Arg399Gln), and The Risk of Age-Related Cataract: A Meta-Analysis

Purpose: A meta-analysis of available studies was used to test the association between two DNA repair genes and age-related cataract.Materials and Methods: A systematic search of the Chinese National Knowledge Infrastructure, EMBASE and PubMed databases identified six studies that were analyzed. Meta-analysis was used to evaluate single nucleotide polymorphisms (SNP) of the DNA repair gene xeroderma pigmentosum complementation group D (XPD) (Lys751Gln) and the X-ray repair cross-complementing gene 1 (XRCC1) (Arg399Gln). Only articles published before June 6, 2014, were included. The quality of the studies was determined using Newcastle–Ottawa Scale tools. The summary odds ratio (OR) and corresponding confidence interval (CI) for XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms and risk of age-related cataract were estimated by random and fixed-effects models. Sensitivity analysis was employed to determine the robustness of the conclusions.Results: Six studies, with a total of 1518 patients with cataractous lenses and 1437 subjects with clear lenses, were included in the meta-analysis. XRCC1 Arg399Gln polymorphisms were associated with cataract risk (recessive model: ORfixed = 0.79, 95% CI: 0.67–0.93; dominant model: ORfixed = 0.84, 95% CI: 0.64–1.11; additive model: ORfixed = 0.82, 95% CI: 0.72–0.92). Analysis of Chinese, but not non-Chinese subgroups, confirmed this association. The OR of XPD Lys751Gln polymorphisms for cataract was not significant. The associations remained significant after sensitivity analysis.Conclusions: This meta-analysis indicates that XRCC1 Arg399Gln polymorphisms, but not XPD Lys751Gln polymorphisms, are associated with risk of age-related cataract.

Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy.

This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III β-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin- based first-line treatment were analyzed. These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.