X-ray Repair Cross-complementing Group 1 Arg399Gln Research Articles

Association between XRCC1 Arg399Gln polymorphism with prognosis of head and neck squamous cell carcinomas: A meta-analysis

ObjectiveThe X-ray repair cross complementing group 1 (XRCC1) gene is involved in DNA repair. Defects in DNA repair may lead to head and neck squamous cell carcinomas (HNSCCs). Several researches have focused on relationship between XRCC1 Arg399Gln genetic polymorphism with HNSCC's prognosis with conflicting results. So, the aim of the present meta-analysis was evaluation of relationship between XRCC1 Arg399Gln polymorphism with HNSCC's prognosis. MethodsPublished articles up to July 2022 were systematically searched through international databases like PubMed, Web of Science, Scopus, etc. I2 test was applied to assess the heterogeneity. Data were analyzed using random effects model. Funnel plots and Egger test were applied for assessing publication biases. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated for evaluation of relationship between the polymorphism with HNSCC's prognosis. ResultsFifteen articles were included for the systematic review. Six of those articles were considered for inclusion in meta-analysis. The different forms of XRCC1 Arg399Gln polymorphism had not significant association with overall survival (OS) under varied genetic models (heterozygous: Ln (HR) = 0.02, 95 % CI= (−0.33,0.37), p-value = 0.90; homozygous: Ln (HR) = 0.33, 95 % CI= (−0.03,0.69), p-value = 0.07 and dominant: Ln (HR) = 0.06, 95 % CI = (−0.17,0.28), p-value = 0.62). Analysis showed that variants of the polymorphism had no significant relationship with OS in Asian and Caucasian ethnicity under dominant model (Ln (HR) = 0.14, 95 % CI= (−0.13,0.40), p-value = 0.31; Ln (HR) = -0.01, 95 % CI= (−0.41,0.38), p-value = 0.96). ConclusionDifferent forms of XRCC1 Arg399Gln polymorphism had no significant relationship with HNSCC's prognosis under varied genetic models and based on different ethnicity.

Gene Polymorphism of XRCC1 in Systemic Lupus Erythematous

Introduction: There are debates about the role of the X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln gene in the pathogenesis of Systemic Lupus Erythematosus (SLE). Methods: The study was a case-control study carried out on 100 recently diagnosed SLE patients compared to 100 control subjects. The study of XRCC1 Arg399Gln polymorphism was performed by a polymerase chain reaction and restriction fragment length polymorphism. Results and Discussion: A higher frequency of ‘G’ allele in SLE (38.5%) versus control (32%) was noticed; however, this difference was not statistically significant (p = 0.174). Besides, a slightly higher frequency of G/G genotype was found in SLE (22%) vs. control (12%); again, this difference was not statistically significant (p = 0.157). A statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p = 0.010, 0.032, and 0.036, respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). Otherwise, there was no statistically significant difference between the three genotypes regarding other parameters: photosensitivity, malar rash, oral ulceration, ANA, anti-dsDNA antibody, anemia, leucopenia, neurologic manifestations, and all lab parameters except hemoglobin level. Similar results were reported previously. According to genotype, in the study of Clinical and laboratory parameters in SLE patients, a statistically significantly higher proportion of arthritis, serositis, and thrombocytopenia was observed in the A/A genotype (p =0 .01, 0.032, and 0.036 respectively). Furthermore, we noticed a statistically significant lower hemoglobin level in G/G genotype (p = 0.027). These findings suggest a pathogenic connection between the seriousness of the defective DNA repair and the autoimmune severity; such connection is consistent with that found in several murine models. Additionally, negative regulation of the genes encoding the proteins involved in the NER pathway in SLE patients, specifically and XPC, has been found previously. Conclusion: The present study highlights the higher insignificant increase of G allele and GG genotype of XRCC1 399 gene in patients with SLE compared to healthy control. This increase was significantly associated with anemia in patients, which may reflect the aggravation of environmental risk factors to SLE associated with the reduced repair of DNA. Further longitudinal studies are required to validate the present findings.

Genetic and biochemical studies of hepatic carcinoma in the Egyptian population.

Background:Hepatocellular carcinoma (HCC), a deadly malignancy of the liver, is considered the third leading reason behind cancer deaths. It is more frequent in men than in women of ages above 50. Liver disease, leading to liver cirrhosis (LC), is mostly caused by alcoholism abuse, reaction diseases of the liver, or viral hepatitis B or C infection. Interleukin-6 (IL-6) is considered an effective pro-inflammatory cytokine, which plays a crucial role in the host defense mechanism. Its level is higher in HCC patients than in LC cases, indicating that tumor cells increase the production of cytokines. The X-ray repair cross-complementing group 1 (XRCC1) gene is a major DNA repair gene. It acts as a scaffold of various activities that are concerned in the repairing method by interacting with components of base excision repair. This study aims to measure the serum concentrations of IL6 and C-reactive protein (CRP) and investigate whether XRCC1 Arg194Trp and Arg399Gln polymorphisms are related to HCC disease.Materials and Methods:Whole-blood DNA was extracted from 123 HCC patients and 123 healthy volunteers. Tetra-primer amplification refractory mutation system was performed in the detection of XRCC1 Arg399Gln and Arg194Trp polymorphisms.Results:Serum concentration levels of IL-6 and CRP are significantly higher in patients with HCC than in control subjects. The allelic and genotype frequency distributions of XRCC1 (Arg399Gln and Arg194Trp) are significantly increased in HCC cases compared to healthy volunteers.Conclusion:Arg/Gln, Arg/Trp, Gln/Gln, and Trp/Trp genotypes are associated with higher risk HCC than the Arg/Arg genotype.

The Association Between the XRCC1 Arg399Gln Polymorphism and the Risk of Head and Neck Cancer: An Updated Meta-Analysis Including 14586 Subjects.

Background:Accumulated evidence shows that DNA repair gene X-ray repair cross complementing group 1 (XRCC1) may determine individual susceptibility to head and neck cancer (HNC) as a major DNA repair gene. However, the results from previous studies have been conflictive and inconsistent. In order to more accurately estimate and integrate the association between XRCC1 Arg399Gln polymorphism and HNC risk, we conducted a meta-analysis including 14586 subjects.Methods:In this meta-analysis, literatures were collected up until September 15, 2020 through multifarious retrieval strategies by searching through electronic databases of PubMed, Cochrane Library, EMBASE, Medline, Web of Science and CNKI. The association between the XRCC1 Arg399Gln polymorphism and HNC was analyzed through calculating summary odds ratios (OR) and 95% confidence intervals (CI).Results:Thirty-one studies consisting of 6025 cases and 8561 controls were identified and analyzed. No significant association between XRCC1 Arg399Gln polymorphisms and HNC risk was found under the allelic (OR = 0.94, 95% CI: 0.82-1.07, P = 0.35), homozygous (OR = 0.99, 95% CI: 0.81-1.21, P = 0.91), heterozygous (OR = 1.01, 95% CI: 0.90-1.13, P = 0.91), dominant (OR = 1.05, 95% CI: 0.85-1.29, P = 0.67) or recessive (OR = 0.93, 95% CI: 0.80-1.08, P = 0.35) genetic models in the overall comparison. In addition, subgroup analyses according to tumor site also displayed no significant association between XRCC1 Arg399Gln polymorphisms and HNC risk. However, subgroup analyses based on ethnicity indicated that HNC risk was significantly related to Arg399Gln genetic heterozygous model (OR = 1.21, 95%CI: 1.04-1.42, P = 0.02) and dominant model (OR = 1.27, 95%CI: 1.02-1.60, P = 0.04) in Caucasians populations.Conclusion:The results from this meta-analysis suggest that the XRCC1 Arg399Gln variants (Arg/Gln and Arg/Arg+Arg/Gln) may contribute to high HNC risk among Caucasians. Further well-designed studies and larger sample sizes are needed to validate our findings.

A DNA Repair Pathway Polymorphism (rs25487) and Angiographically Proven Coronary Artery Patients in a Population of Southern Iran.

Coronary Artery Disease (CAD), which is a multifactorial genetic disease, is known as one of the most common causes of death worldwide. In this regard, X-ray Repair Cross-Complementing group 1 (XRCC1), a DNA repair protein involved in Single-Strand Breaks (SSBs), and Base Excision Repair (BER) pathways have been reported to be responsible for the efficient repair of single strand breaks and damaged bases in DNA. In the current study, we analyzed Arg399Gln (rs25487), which is one of the most common polymorphisms of XRCC1 gene that might be associated with the increased risk for CAD. This case-control study was performed to investigate the relationship between this polymorphism and CAD development. In this study, 290 patients and 216 controls were diagnosed by cardiac angiography and then screened for the above-mentioned polymorphism using Restriction Fragment Length Polymorphisms (RFLP) method. The frequency of the GA genotype of XRCC1 Arg399Gln (rs25487) was significantly higher in CAD patients compared to the controls (p=0.002, OR: 1.21, 95% CI: 1.06-1.37). Moreover, its dominant mode (AA + GA) genotype had a 1.851-fold increase in the risk of CAD (p = 0.005). Our findings demonstrated that Arg399Gln polymorphism of XRCC1 (rs25487) has a significant relationship with CAD and also plays a probable predisposing role in that. Our results support the role of DNA damages and the malfunctions of DNA repair system in the patients with CAD.

The Ability of Polymorphisms in DNA Repair Enzymes to Predict Clinical Outcome in Colorectal Cancer Patients

Background: Genomic polymorphisms of DNA repair enzymes/excision repair cross complementation group 1 (ERCC1), excision repair cross complementation group 2 (ERCC2), and X-ray repair cross complementation group 1 (XRCC1) correlate with survival and therapeutic responses in colorectal cancer (CRC) patients. Therefore, the present study examined the frequency of ERCC1 C118T, ERCC2 Lys751Gln, and XRCC1 Arg399Gln polymorphisms and their prognostic and predictive values in CRC patients. Method: In this retrospective study, a total of 143 CRC patients were evaluated for these polymorphisms by PCR-RFLP. Results: The majority of the patients showed heterozygous C/T (56%) compared to wild type C/C (29%) and variant T/T (15%) genotypes for ERCC1 C118T polymorphism. ERCC2 Lys751Gln polymorphism showed wild type A/A (44%), heterozygous A/C (40%), and variant C/C genotypes (16%). The frequency of XRCC1 Arg399Gln polymorphism was 48% (wild type G/G), 42% (heterozygous G/A), and 10% (variant A/A). The relapse-free survival (RFS) significantly decreased in patients with ERCC1 118 C/C wild type genotype in the subgroups of patients with advanced stage and colon cancer; however, variant T/T genotype correlated with reduced overall survival (OS) in patients treated with combined drug 5-FU/Oxaliplatin. Taken together, in CRC patients and patients treated with 5-FU/Oxaliplatin, ERCC2 Lys751Gln A/A wild type genotype led to significantly unfavorable clinical outcomes. However, XRCC1 Arg399Gln polymorphism did not show any significant association with prognosis. Additionally, on analyzing combined effect of ERCC1 and ERCC2 polymorphisms, a significant reduced OS in patients with both unfavorable genotypes (ERCC1: C/C and ERCC2: A/A) was found. Furthermore, in the subgroup of patients treated with 5-FU/Oxaliplatin, RFS and OS significantly decreased in patients with both unfavorable genotypes (ERCC1: T/T and ERCC2: A/A). Conclusion: The significant relationship of ERCC1 C118T and ERCC2 Lys751Gln polymorphisms with prognosis and treatment response reflects the vital role of these molecules as prognostic and predictive markers in patients with CRC. Additionally, the combined evaluation of ERCC1 and ERCC2 polymorphisms might identify high risk CRC patients with poor prognosis.

Association between X‐ray repair cross‐complementing group 1 Arg399Gln polymorphism and male infertility: An update meta‐analysis

Numerous studies concentrate on the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta-analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A-allele vs. G-allele: OR=1.183, p=.003), heterozygote genetic model (AA vs. GA: OR=1.256, p=.027), recessive genetic model (AA vs. GG+GA: OR=1.279, p=.012) and dominant genetic model (AA+GA vs. GG: OR=1.218, p=.026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A-allele vs. G-allele: OR=1.145, p=.025) with rare heterogeneity (I2 =0%). In summary, our meta-analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A-allele might be a risk factor for this disease, especially in Asians.

Association between polymorphisms in the XRCC1 gene and male infertility risk: A meta-analysis.

Background:X-ray repair cross-complementing group 1 (XRCC1) single nucleotide polymorphisms (SNPs) might correlate with male infertility susceptibility. This association has been described; however, the findings remain inconsistent. Consequently, this meta-analysis was conducted to characterize the relationship between XRCC1 SNPs and male infertility susceptibility.Methods/main results:Studies were systematically searched in databases to evaluate the association between SNPs of XRCC1 and infertility in males. The effect measures chosen were the 95% confidence intervals (95% CIs) and odds ratios (ORs). A total of 7 studies, including 6 case-controlled studies on XRCC1 Arg399Gln and 3 case-controlled studies on XRCC1 Arg194Trp, were included. Ultimately, the results of this analysis revealed that XRCC1 Arg399Gln SNPs were significantly associated with infertility in males in homozygote comparisons (GG vs GA+AA: OR = 0.614, 95% CI: 0.40–0.937, P = .024). This meta-analysis did not demonstrate a relationship between XRCC1 Arg194Trp and male infertility risk.Conclusions:Our study indicated that XRCC1 Arg399Gln polymorphism was associated with a significantly decreased male infertility risk, but not XRCC1 Arg194Trp.

The Possible Role of XRCC1 Gene Polymorphisms with Idiopathic Non-obstructive Azoospermia in Southeast Turkey.

X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing DNA damage during spermatogenesis. We examined the effects the possible role of two single nucleotide polymorphisms of XRCC1 Arg194Trp and Arg399Gln in DNA repair gene XRCC1 with risk of idiopathic non-obstructive azoospermia (INOA) in a south-east Turkey population. The genotype and allele frequencies of two observed polymorphisms of XRCC1 Arg194Trp and Arg399Gln were examined by polymerase chain reaction-restriction fragment length polymorphism in 102 infertile men with INOA and 102 fertile controls. In our study, all the observed genotype frequencies are in agreement with Hardy-Weinberg equilibrium. The genotype frequencies of the XRCC Arg194Trp were 84% (CC), 16% (CT) and 2% (TT) among the men with INOA, while the frequencies of those genotypes in the controls were found to be 88% (CC), 12% (CT) and 2% (TT) (?2 test: P < .05). Similarly, the genotypes frequencies of GG, GA, and AA of the XRCC1 Arg399Gln were 44%, 39%, and 19% in the group of men with INOA, whereas these frequencies were 42%, 45%, and 15% in the control group, respectively. No significant difference between the control group and the men with INOA were found in the frequencies of genotypes and allele of XRCC1 Arg194Trp and Arg399Gln (P > 0.05). Neither Arg194Trp nor Arg399Gln polymorphisms in the XRCC1 gene influenced risk of INOA in our study. However, these findings may be helpful in improving the understanding of the etiology of male infertility.

The polymorphism of XRCC1 Arg399Gln (rs25487) and male infertility risk: a meta-analysis of 1,407 cases and 974 control studies.

X-ray repair cross-complementing group 1 (XRCC1) is a scaffold protein and a key element in DNAbase excision repair process.Although, the role of XRCC1 polymorphisms in male infertility has been studied broadly, it is still a matter of debate. Hence, in order to shed light on the problem, we performed a meta-analysis to evaluate the overall effect of XRCC1 polymorphisms in male infertility risk. Databases, Web of Science, PubMed, Scopus, and Google Scholar were searched until September 15, 2018. Afterwards, the genotypes' distribution, genotyping methods, and ethnicity groups were extracted, and overall analyses were conducted. A total number of five researches on 1,407 subjects and 974 controls were found to meet our criteria in this meta-analysis. The XRCC1Arg399Gln (rs25487)polymorphism was analyzed. This is the first meta-analysis to investigate the association of XRCC1 polymorphisms (codon 399) and male infertility risk. Our results indicated that the XRCC1 Arg399Gln polymorphism was not associated with male infertility risk in the total studied populations (Tab. 2, Fig. 3, Ref. 26). Keywords: meta-analysis; male infertility; polymorphism; XRCC1 Arg399Gln.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

Associations between three XRCC1 polymorphisms and hepatocellular carcinoma risk: A meta-analysis of case-control studies.

Conflicting results have been obtained regarding the association between X-ray repair cross complementation group 1 (XRCC1) and susceptibility to hepatocellular carcinoma (HCC). In this study, associations between HCC and three polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) were evaluated using a meta-analysis approach. PubMed, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang standard database were systematically searched to identify all relevant case-control studies published through March 2018. A total of 32 case-control studies, including 13 that evaluated Arg194Trp, 14 that evaluated Arg280His, and 26 that evaluated Arg399Gln, were analyzed. In the entire study population, XRCC1 Arg399Gln was significantly associated not only with overall risk of HCC (homozygous model, OR = 1.61, 95% CI: 1.40–1.85, P < 0.05; recessive model, OR = 1.40, 95% CI: 1.23–1.59, P < 0.05) but also with the risk of HCC in Chinese patients (homozygous model, OR = 1.78, 95% CI: 1.53–2.08, P < 0.05; recessive model, OR = 1.47, 95% CI: 1.27–1.70, P < 0.05). Limiting the analysis to studies demonstrating Hardy–Weinberg equilibrium (HWE), the results were consistent and robust. Similarly, a significant association between XRCC1 Arg399Gln and HCC risk was found in healthy controls in the general population but not in hospital controls. Trial sequential analysis (TSA), false-positive report probabilities (FPRP), and combined genotype analysis revealed that XRCC1 Arg399Gln is mainly associated with susceptibility to liver cancer. However, there was no association between Arg194Trp or Arg280His and the risk of HCC. These results, indicating that the Arg399Gln polymorphism of XRCC1 is associated with the risk of HCC in the Chinese population, provide a basis for the development of improved detection and treatment approaches.

The X-ray Repair Cross-Complementing Group 1 Arg399Gln Genetic Polymorphism and Risk of Hepatocellular Carcinoma in an Iranian Population.

BACKGROUND The association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln gene polymorphism and hepatocellular carcinoma (HCC) has been investigated in several populations. However, the findings are controversial. The aim of this study was to address the association between XRCC1 Arg399Gln polymorphism and HCC in an Iranian population. METHODS We have evaluated the association between XRCC1 Arg399Gln gene polymorphism and HCC in 151 Iranian individuals (50 patients with HCC and 101 healthy matched controls) using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS Significant association was found for the XRCC1 A allele and HCC [OR = 1.93, 95% CI (1.16 - 3.25), P = 0.0099]. Also, genotype analysis by SNPStats online software showed a significant association between XRCC1 gene polymorphisms and HCC under co-dominant, dominant, and recessive genetic models. CONCLUSION Our study provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with the risk of HCC development in Iranian population.

Lack of correlation between X-ray repair cross-complementing group 1 gene polymorphisms and the susceptibility to colorectal cancer in a Malaysian cohort.

X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.

Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility

ABSTRACTSperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility.

Association between X-ray repair cross-complementing group 1(XRCC1) Arg399Gln polymorphism and endometriosis: A systematic review and meta-analysis

Objective(s)X-ray repair cross-complementing group 1(XRCC1) gene is one of the DNA repair pathway genes playing a vital role in endometriosis risk. Various studies have explored the association between them, however, the results remained inconsistent. So to confirm the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis, a meta-analysis was conducted. Study designPubMed, Web of Science, Science Director, Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases were searched to identify the all relevant studies before Sep. 30, 2016 focusing on the association between XRCC1 Arg399Gln polymorphism and the risk of endometriosis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and analyzed by Review Manager 5.2 and Stata 12 to assess the strength of the association. Meanwhile, Begg’s test was used to check the publication bias. ResultsThe present meta-analysis identified 6 studies with 646 cases and 616 controls. The overall analysis revealed that the AA genotype exhibited a significant association with a decreased risk for endometriosis compared with GG (OR=0.43, 95%CI=0.20–0.94, P=0.03), GA (OR=0.57, 95%CI=0.35–0.95, P=0.03) and GG+GA (OR=0.54, 95%CI=0.31–0.96, P=0.04) respectively. In addition, subgroup analyses based on varied regions indicated that a total comparisons of allelic and various genetic models had statistical significances among Asians (A allele vs. G allele: OR=0.62, 95%CI=0.48–0.81, P=0.0004; AA vs. GG: OR=0.22, 95%CI=0.11–0.46, P<0.0001; AA vs. GA: OR=0.32, 95%CI=0.16–0.63, P=0.001; AA vs. GG+GA: OR=0.28, 95%CI=0.14–0.54, P=0.0002; AA+GA vs. GG: OR=0.28, 95%CI=0.14–0.54, P=0.008) but not among Middle Eastern. The Begg’s test did not reveal any obvious publication bias in the present study. Conclusion(s)Our meta-analysis suggested that Arg399Gln in XRCC1 was associated with endometriosis risk. And especially in Asians, the A allele might be a preventive factor for this disease. Further well-designed researches with larger sample size and various regions are required to validate our conclusion.

The polymorphism XRCC1 Arg194Trp and 8-hydroxydeoxyguanosine increased susceptibility to arsenic-related renal cell carcinoma

This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification. Genomic DNA was used to examine the genotype of XRCC1(Arg399Gln), XRCC1(Arg194Trp), XRCC3(Thr241Met) and XPD(Lys751Gln) by PCR-RFLP. Liquid chromatography with tandem mass spectrometry was used to determine urinary 8-OHdG levels. A HPLC-HG-AAS was used to determine the concentrations of urinary arsenic species. Participants with the genotype XRCC1(Arg194Trp) Arg/Trp+Trp/Trp had a significantly higher OR of RCC than those with the Arg/Arg genotype; the OR and 95% confidence interval was 0.66 (0.45–0.97) after multivariate adjustment. The OR of RCC for the combined effect of high urinary 8-OHdG levels and high urinary total arsenic concentration in individuals with a XRCC1(Arg194Trp) Arg/Trp+Trp/Trp genotype was higher than in patients with an Arg/Arg genotype, which was evident in a dose response manner. In conclusion, this is the first study to show that the XRCC1 Arg194 allele is a predicting factor for RCC. The more risk factors (high urinary 8-OHdG levels, high urinary total arsenic concentrations, and XRCC1 Arg194 allele) that were present, the higher the OR of RCC.

New Concept of X-Ray Repair Cross-Complementing Groups 1 Polymorphisms and Gynecologic Cancer Risk

Background: Several meta-analyses have been conducted to examine the possible link between X-ray repair cross-complementing groups 1 (XRCC1) Arg399Gln polymorphism and cervical cancer risk. However, the results are controversial. Therefore, we carried out a more comprehensive meta-analysis to examine whether XRCC1 polymorphisms are associated with general gynecologic cancer risk. Methods: Twenty studies, comprising 4,230 cases and 5,458 controls that included analyses of XRCC1 polymorphisms (Arg194Trp, Arg280His, or Arg399Gln) were included in our study. Results: Overall, no significant association between any of the studied XRCC1 polymorphisms and gynecologic cancer risk was observed. However, in further stratified analyses, the Arg399Gln was definitely associated with increased gynecologic cancer risk in Asians (A vs. G: OR 1.24; 95% CI 1.02-1.53), which was also associated with increased cervical cancer risk (A vs. G: OR 1.20; 95% CI 1.00-1.44). Similarly, the Arg194Trp was significantly associated with increased gynecologic cancer risk in Asians (TT vs. CC: OR 1.87; 95% CI 1.02-3.42) and endometrial cancer (T vs. C: OR 1.45; 95% CI 1.05-2.02). Conclusions: These findings provided evidence that XRCC1 Arg399Gln and Arg194Trp variants may modify the susceptibility to gynecologic cancers based on ethnicity and type. Further studies with large sample size are warranted to extend our findings.

Meta-analysis of associations between XRCC1 gene polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis.

To determine whether X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of nine case-control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta-analysis. This meta-analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139-1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630-0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554-0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk.

Assessment of the Link between XRCC1 Arg399Gln Polymorphism and Breast Cancer: a Meta-Analysis in a Single Ethnic Group.

Although various individual studies have been conducted to determine the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and breast cancer, the results remain inconclusive. To assess the influence of XRCC1 Arg399Gln polymorphism on the risk of breast cancer, a metaanalysis was performed in a single ethnic group. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout February 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of the associations. Ten studies documenting a total of 4732 breast cancer cases and 5677 controls were included in this metaanalysis. The results indicated no significant association between XRCC1 Arg399Gln polymorphism and breast cancer risk in both total analysis and subgroup analysis stratified by geographical areas and source of controls. This meta-analysis provided evidence that XRCC1 Arg399Gln variant might not be risk alleles for breast cancer susceptibility in the Chinese population. Further studies conducted in other ethnic groups are required for definite conclusions.