X-ray Repair Cross-complementing Group Research Articles

Three polymorphisms of DNA repair gene XRCC1 and the risk of glioma: a case–control study in northwest China

Three polymorphisms of X-ray repair cross-complementing groups 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln may be associated with the individual susceptibility to glioma. The aim of this study was to investigate any association between three polymorphisms of the XRCC1 gene at codon 194, 280, and 399 and potential glioma risk. We conducted a hospital-based case-control study in northwest China. A total of 1,772 subjects, including 886 glioma patients and 886 healthy controls, were recruited in this study. The peripheral blood samples were extracted. Polymerase chain reaction-restriction fragment length polymorphism method was used to test genotypes. Glioma patients had a significantly higher frequency of XRCC1 194 TT (odds ratio [OR] = 1.76, 95 % confidence interval [CI] = 1.14, 2.72; P = 0.01) and XRCC1 399 AA genotype (OR = 1.62, 95 % CI = 1.09, 2.40; P = 0.02) than controls. When stratified by the grade of glioma, patients with WHO IV glioma had a significantly higher frequency of XRCC1 194 TT (OR = 1.60, 95 % CI = 1.02, 2.51; P = 0.04) and XRCC1 399 AA genotype (OR = 1.59, 95 % CI = 1.04, 2.42; P = 0.03). When stratified by the histology of glioma, there was no significant difference in the distribution of each genotype. This study suggested that XRCC1 Arg194Trp and Arg399Gln polymorphisms were associated with the risk of glioma.

Correlation between X-ray cross-complementing group 1 polymorphisms and the onset risk of glioma: A meta-analysis.

OBJECTIVE:To evaluate the association of X-ray cross-complementing group 1 (XRCC1) Arg399Gln, 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 database 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 Arg399Gln, Arg194Trp, and Arg280His polymorphisms with the risk of glioma, and subgroup analyses were performed according to different ethnicities of the subjects.RESULTS:Twelve articles were included in the meta-analysis. Eleven of the articles were concerned with the Arg399Gln polymorphism and glioma onset risk. Significantly increased glioma risks were found only in the dominant model (Gln/Gln + Gln/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 subjects. 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 Arg399Gln polymorphism may be a biomarker of glioma susceptibility, especially in Asian populations. The Arg194Trp and Arg280His polymorphisms were not associated with overall glioma risk.

DNA Repair Gene XRCC1 Polymorphisms, Smoking, and Bladder Cancer Risk: A Meta-Analysis

Background and ObjectiveThe X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study.MethodsPubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status.ResultsA total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211–3.621, P=0.008 for R280H, respectively).ConclusionsThis meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.

Association between XRCC3 Thr241Met polymorphism and risk of brain tumors: a meta-analysis

X-ray repair cross-complementing group 3 (XRCC3) plays an important role in the process of homologous recombination repair for DNA double-strand breaks which further maintains the stability of the genome. XRCC3 Thr241Met polymorphism has been indicated in the development of cancers, but the association of the XRCC3 Thr241Met polymorphism with risk of brain tumors is still unclear owing to the conflicting findings from previous studies. We performed a meta-analysis to provide a better understanding on the association between the XRCC3 Thr241Met polymorphism and risk of brain tumors. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was used to assess the association. Thirteen case-control studies involving a total of 4,984 cases and 7,472 controls were included. Overall, there was no statistically significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors under all contrast models. Subgroup analysis by race suggested that the XRCC3 Thr241Met polymorphism was associated with increased risk of brain tumors in Asians under all four contrast models (Met vs. Thr: OR = 1.22, 95 % CI 1.09-1.36, P < 0.01; MetMet vs. ThrThr: OR = 1.89, 95 % CI 1.38-2.57, P < 0.01; MetMet vs. ThrThr/ThrMet: OR = 1.78, 95 % CI 1.31-2.40, P < 0.01; and MetMet vs. ThrThr/ThrMet: OR = 1.19, 95 % CI 1.04-1.36, P = 0.01). However, there was no significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors in Caucasians. Therefore, the XRCC3 Thr241Met polymorphism is associated with increased risk of brain tumors, especially in Asians.

Predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients: meta-analysis

Previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcome of platinum-based chemotherapy in patients with lung cancer reported conflicting results. A meta-analysis was performed to provide a systematic review of the published data. We retrieved the relevant studies from PubMed and Embase databases. The primary outcome was overall survival, and the hazard ratio (HR) with 95% confidence interval (95% CI) was estimated. Seven studies with a total of 1,514 patients were included into the meta-analysis. Overall, XRCC3 Thr241Met polymorphism had no influence on the overall survival of lung cancer patients receiving platinum-based chemotherapy (MetMet vs. ThrThr: HR = 0.82, 95% CI 0.52-1.31, P = 0.410; MetThr vs. ThrThr: HR = 0.93, 95% CI 0.79-1.10, P = 0.339; MetMet/MetThr vs. ThrThr: HR = 1.07, 95% CI 0.88-1.31, P = 0.480). There was no obvious risk of publication bias. Therefore, currently available data suggest that there is no predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients.

Comprehensive assessment of the association between DNA repair gene XRCC3 rs861539 C/T polymorphism and lung cancer risk

A few case-control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case-control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89-1.13), P = 0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81-1.41), P = 0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84-1.07), P = 0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86-1.39), P = 0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.

Association between XRCC1 and XRCC3 Polymorphisms with Lung Cancer Risk: A Meta-Analysis from Case-Control Studies

Many studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp, Arg280His, −77T>C, and X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphisms with lung cancer risk, but the results remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), −77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models. We found that −77T>C polymorphism was associated with increased lung cancer risk (dominant model: odds ration [OR] = 1.45, 95% confidence interval [CI] = 1.27–1.66, recessive model: OR = 1.73, 95% CI = 1.14–2.62, additive model: OR = 1.91, 95% CI = 1.24–1.94) when all the eligible studies were pooled into the meta-analysis. In the stratified and sensitive analyses, significantly decreased lung cancer risk was observed in overall analysis (dominant model: OR = 0.83, 95% CI = 0.78–0.89; recessive model: OR = 0.90, 95% CI = 0.81–1.00; additive model: OR = 0.82, 95% CI = 0.74–0.92), Caucasians (dominant model: OR = 0.82, 95% CI = 0.76–0.87; recessive model: OR = 0.89, 95% CI = 0.80–0.99; additive model: OR = 0.81, 95% CI = 0.73–0.91), and hospital-based controls (dominant model: OR = 0.81, 95% CI = 0.76–0.88; recessive model: OR = 0.89, 95% CI = 0.79–1.00; additive model: OR = 0.80, 95% CI = 0.71–0.90) for XRCC3 T241M. In conclusion, this meta-analysis indicates that XRCC1 −77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.

DNA repair gene XRCC1 polymorphisms and susceptibility to childhood acute lymphoblastic leukemia: a meta-analysis.

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). 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). 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. XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.

X-ray repair cross-complementing group 1 codon 399 polymorphism and lung cancer risk: an updated meta-analysis

Many epidemiologic studies have investigated the association between x-ray repair cross-complementing group 1 gene (XRCC1) codon 399 polymorphism and lung cancer risk, but the results were inconsistent. We performed a meta-analysis of 46 studies on XRCC1 codon 399 polymorphism and lung cancer risk published before June 2013. In general population, the M allele and MM genotype were associated with increased risk of lung cancer compared with C allele and CC genotype, and the ORs were 1.06 (95% CI 1.01-1.12) and 1.19 (95% CI 1.05-1.34), respectively. When it was stratified according to Asian population, the association between XRCC1 codon 399 polymorphism and lung cancer risk was further strengthened. The ORs of comparison between M vs. C, MM vs. CC, and MM vs. CM + CC were 1.14 (95% CI 1.03-1.26), 1.41 (95% CI 1.11-1.78), and 1.38 (95% CI 1.12-1.71), respectively. The association between codon 399 polymorphism and lung cancer risk in nonsmoking Chinese women was stronger than any other subgroups. However, no associations were found in the Caucasian and African population. This meta-analysis has demonstrated that codon 399 polymorphism of XRCC1 gene might contribute to individual's susceptibility to lung cancer in Asian population, and especially in nonsmoking Chinese women. Future studies focused on interactions between combined genes and environmental risk factors are warranted.

Association of XRCC3 and XRCC4 gene polymorphisms, family history of cancer and tobacco smoking with non-small-cell lung cancer in a Chinese population: a case–control study

Single-nucleotide polymorphisms (SNPs) of DNA repair genes have been reported to modify cancer risk. This study aimed to determine SNPs of the DNA repair genes X-ray repair cross-complementing group 3 (XRCC3) and X-ray cross-complementing group 4 (XRCC4) and their association with non-small-cell lung cancer (NSCLC) susceptibility in a Chinese population. A total of 507 NSCLC patients and 662 healthy controls were recruited for genotyping. Epidemiological and clinical data were also collected for association studies. The data showed that the rs1799794 G allele in the XRCC3 gene and minor allele carriers of XRCC4, including rs1056503 and rs9293337, were inversely associated with NSCLC risk (GG vs homozygote AA), whereas the rs861537 AG or AA genotype and XRCC4 rs6869366 had a significantly increased NSCLC risk. Furthermore, tobacco smoking over 26 pack-years, a family history of lung cancer, exposure to environmental tobacco smoke (ETS) and negative mental status were risk factors for developing NSCLC. This study suggests that SNPs of XRCC3 and XRCC4 and other environmental factors are risk factors for developing NSCLC in this Chinese Han population.

Association between the Thr241Met polymorphism of X-ray repair cross-complementing group 3 gene and glioma risk: evidence from a meta-analysis based on 4,136 cases and 5,233 controls

Genetic polymorphism of X-ray repair cross-complementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of glioma, but the results are controversial. Medline, PubMed, Embase, and Cochrane Library databases were independently searched by two investigators up to 13 July 2013. Summary odds ratios (OR) and 95% confidence interval (CI) for Thr241Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Stata 12.0. A total of 10 independent studies, including 4,136 cases and 5,233 controls, were identified. Our analysis suggested that Thr241Met was not associated with glioma risk in overall population. In the subgroup analysis, we detected no significant association between Thr241Met polymorphism and glioma risk in different descent populations. Subgroup analysis was held by source of controls, significant association was found between this polymorphism and glioma risk for population-based studies (homozygote model: OR = 1.747, 95% CI = 1.123-2.717, Ph = 0.059, I(2) = 59.7%; recessive model, OR = 1.455, 95% CI = 1.179-1.795, Ph = 0.111, I(2) = 50.1%; allele model, OR = 1.258, 95% CI = 1.010-1.566, Ph = 0.011, I(2) = 72.9%). This meta-analysis showed the evidence that XRCC3 Thr241Met polymorphism was associated with a low risk of glioma development.

Genetic polymorphisms in XRCC1 gene and susceptibility to glioma in Chinese Han population

Glioma is the most common type of primary brain malignancy in adults. The X-ray repair cross-complementing group 1 (XRCC1) is an important candidate gene for influencing the pathogenesis of glioma. This study aimed to evaluate the potential association between XRCC1 genetic polymorphisms and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 620 glioma cases and 630 cancer-free controls. XRCC1 genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and verified using DNA sequencing methods. The c.910A>G and c.1779C>G genetic polymorphisms were identified in this study. Our data suggested that the genotypes/alleles of these two genetic polymorphisms were statistically associated with the increased risk of glioma. As for c.910A>G, the risk of glioma for genotype GG was significantly higher than wild genotype AA (odds ratio (OR) = 1.98, 95% confidence interval (CI) 1.33-2.94, P = 0.001). As for c.1779C>G, the genotype GG was statistically associated with the increased risk of glioma compared to wild genotype CC (OR = 1.80, 95% CI 1.17-2.78, P = 0.007). Both of alleles G in c.910A>G and c.1779C>G may contribute to glioma susceptibility (G versus (vs.) A, OR = 1.30, 95% CI 1.09-1.54, P = 0.003; G vs. C, OR = 1.19, 95% CI 1.00-1.42, P = 0.045). Our findings indicate that the c.910A>G and c.1779C>G genetic polymorphisms are associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36- 2.36, P=0.00; TT vs. OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.

Association of XRCC1 gene single nucleotide polymorphisms and susceptibility to pancreatic cancer in Chinese

The human X-ray repair cross-complementing group 1 gene (XRCC1) is an important candidate gene for affecting pancreatic cancer (PC) risk. The objective of this study was to detect whether the c.1471G > A and c.1686C > G polymorphisms of XRCC1 gene influence PC risk. The association of XRCC1 genetic variants with PC risk was analyzed in 328 PC patients and 350 controls by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction method. Our data suggested that the genotypes and alleles from these two genetic variants were statistically associated with PC risk. For c.1471G > A, the AA genotype was associated with the decreased risk of developing PC compared to GG wild genotype (odds ratio (OR) = 0.43, 95% confidence intervals (CI) 0.26-0.70, chi-squared (χ(2)) = 11.91, P = 0.001). For c.1686C > G, the risk of PC was significantly lower for GG genotype in comparing to CC wild genotype (OR = 0.48, 95% CI 0.29-0.81, χ(2) = 7.98, P = 0.005). The A allele of c.1471G > A and G allele of c.1686C > G genetic variants could contribute to decrease the risk of PC (for c.1471G > A: A vs G, OR = 0.65, 95% CI 0.52-0.82, χ(2) = 13.71, P < 0.001, for c.1686C > G: G vs C, OR = 0.70, 95% CI 0.55-0.88, χ(2) = 9.42, P = 0.002). Our findings indicate that the c.1471G > A and c.1686C > G polymorphisms of XRCC1 gene are associated with PC risk in Chinese population.

Assessment of the association between XRCC1 Arg399Gln polymorphism and lung cancer in Chinese

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair and plays an important role in the maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function and repair capacity of XRCC1 protein which further results in the genetic instability and lung carcinogenesis. Previous studies investigating the relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese yielded contradictory results. A meta-analysis was performed to clarify the effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was assessed by calculating the pooled odds ratio (OR) with 95% confidence intervals (95%CI). Nineteen studies with a total of 12,835 participants were included into this meta-analysis. Overall, there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models (Gln vs. Arg: OR = 1.13, 95%CI 1.01-1.25, P = 0.029; GlnGln vs. ArArg: OR = 1.41, 95%CI 1.07-1.84, P = 0.013; GlnGln vs. ArArg/ArgGln: OR = 1.37, 95%CI 1.07-1.76, P = 0.013). Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer under three genetic models. There was no obvious risk of bias in the meta-analysis. Data from the current meta-analysis support the obvious association between XRCC1 Arg399Gln polymorphism and increased risk of lung cancer in Chinese.

Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and colorectal cancer risk

The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a substitution of Arg to Gln at position 194, has been implicated in the development of colorectal cancer (CRC) in a number of case-control studies with contradictory and inconclusive findings. The current meta-analysis of all currently available publications was conducted to assess the gene susceptibility to CRC and improve our understanding of the CRC pathogenesis. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated by use of fixed-effects model or random-effects model when appropriate. A total of 15 eligible case-control studies with 4,501 cases and 8,038 controls were retrieved after a comprehensive search of the PubMed, Embase, Web of science, and Chinese Biomedicine (CBM) databases up to December 2012. The overall meta-analysis identified a positive but not statistically significant association between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast models (ORTrp vs. Arg = 1.07, 95 % CI 0.90-1.26, P OR = 0.441; ORTrpTrp vs. ArgArg = 1.28, 95 % CI 0.91-1.81, P OR = 0.163; ORArgTrp vs. ArgArg = 1.00, 95 % CI 0.85-1.19, P OR = 0.956; ORArgTrp + TrpTrp vs. ArgArg = 1.06, 95 % CI 0.90-1.24, P OR = 0.502; ORTrpTrp vs. ArgArg + ArgTrp = 1.11, 95 % CI 0.91-1.34, P OR = 0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to CRC, although lack statistical evidence (ORTrpTrp vs. ArgArg = 2.69, 95 % CI 0.97-7.49, P OR = 0.058; ORTrpTrp vs. ArgArg + ArgTrp = 2.77, 95 % CI 0.99-7.72, P OR = 0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated with an increased risk of colon cancer. The present meta-analysis suggests that the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon cancer. However, the precise genetic association needs to be further estimated in future studies.

DNA repair gene XRCC3 Thr241Met polymorphism and hepatocellular carcinoma risk

The DNA repair genes have been indicated as candidates in the risk of hepatocellular carcinoma (HCC). Published data on the association between X-ray repair cross-complementing group 3 (XRCC3), a critical member of the DNA repair genes, and HCC risk were contradictory. The aim of this meta-analysis was to assess the effect of XRCC3 Thr241Met polymorphism on HCC risk by pooling available data from published case-control studies. We calculated the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) to estimate the effect. Based on the inclusion criteria, six individual studies with 2,288 cases and 3,170 controls were included into our study. Overall, significant association between the XRCC3 Thr241Met variant and HCC risk was observed under the following contrast models (OR Met vs. Thr = 1.68, 95 %CI 1.08-2.62; OR MetMet vs. ThrThr = 5.54, 95 %CI 3.09-9.94; OR MetMet vs. ThrThr + ThrMet = 5.70, 95 % CI 4.24-7.64). Besides, the pooled ORs indicated that the XRCC3 Thr241Met polymorphism exerted risk effect on the HCC pathogenesis among Asians. Additionally, when stratifying by the status of smoking and hepatitis B virus infection, the XRCC3 Thr241Met variant was significantly associated with HCC risk among the HBsAg (+) individuals but not the HBsAg (-) individuals, smokers, and non-smokers. The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism is an independent risk factor for HCC, particularly among Asians and the HBsAg (+) individuals.

Association of Tyrosyl‐DNA Phosphodiesterase 1 Polymorphism With Tourette Syndrome in Taiwanese Patients

Genetic, environmental, immunological, and hormonal factors contribute to the etiology of Tourette syndrome (TS). From the genetic standpoint, TS is a heterogeneous disorder. In our previous study, we found that a single nucleotide polymorphism (SNP) of x-ray repair cross-complementing group 1 (XRCC1), a DNA repair gene, was associated with TS. Previous studies also showed that tyrosyl-DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is unknown. Therefore, the aim of this study was to test the hypothesis that if the TDP1 SNP, rs28365054 (c.400G>A, Ala134Thr), was associated with TS or not. A case-control study was designed to test the hypothesis. A total of 122 TS children and 106 normal children participated in the study. We used polymerase chain reaction to identify the SNP, rs28365054, of the TDP1 gene in the TS patients and the normal children. A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the TS patients and the control group. The AG genotype was a risk factor for TS with an odds ratio of 2.26 for the AG versus AA genotype (95% CI 1.08-4.72). The findings of this study suggested that variants in the TDP1 gene might play a role in TS susceptibility.

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chi- square or t test and logistic regression analysis by SPSS16.0 software. Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.

Association between X-ray repair cross-complementation group 1 rs25487 polymorphism and pancreatic cancer risk

Previous published studies suggested that genetic polymorphisms in DNA repair genes could modify the DNA repair capacity and could be associated with pancreatic cancer risk. However, previous studies on the association between X-ray repair cross-complementation group 1 (XRCC1) rs25487 (Arg399Gln) polymorphism and pancreatic cancer risk reported inconsistent results. To obtain a more precise estimation of the association between XRCC1 rs25487 polymorphism and pancreatic cancer risk, we performed a meta-analysis of previous published studies by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Eight individual studies with 5,542 subjects from six publications were finally included into this meta-analysis. The meta-analysis of total eight studies showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in total population under all four genetic models (Gln versus Arg: OR = 1.10, 95% CI 0.95-1.28, P = 0.199; GlnGln versus ArgArg: OR = 1.15, 95% CI 0.93-1.41, P = 0.191; GlnGln/ArgGln versus ArgArg: OR = 1.10, 95% CI 0.97-1.25, P = 0.127; GlnGln versus ArgArg/ArgGln: OR = 1.12, 95% CI 0.92-1.36, P = 0.253). Subgroup analysis showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in Caucasians, but XRCC1 rs25487 polymorphism was associated with pancreatic cancer risk in Asians (GlnGln/ArgGln versus ArgArg: OR = 1.24, 95% CI 1.01-1.53, P = 0.040). Therefore, the meta-analysis suggests that XRCC1 rs25487 polymorphism is associated with pancreatic cancer risk in Asians. Further studies with more participants are needed to provide a more precise estimation on the association above.