X-ray Cross-complementing Group Research Articles

“Molecular Characterization And Its Association To Ap Endonuclease-1 (Ape1) And X-Ray Cross-Complementing Group 1 (Xrcc1), As A Dna Repair Protein From Patients With The Risk Of Age-Related Cataract At A Tertiary Care Centre, Uttar Pradesh”

Introduction: Age-related cataract is the leading cause of blindness in the world. (AP)-endonuclease APE1 and the X-ray cross-complementing group 1 (XRCC1) are the key enzymes taking part in the repair of DNA damage. The association of X-ray cross-complementing group 1 (XRCC1) and AP endonuclease-1 (APE1) plays a critical role as polymorphisms of DNA repair genes decreasing the ability to repair DNA damage, leaving human body a greatly increased susceptibility to cancer or age-related diseases.
 Aim and objective: To study the Molecular characterization and its Association to AP endonuclease-1 (APE) and X-ray cross-complementing group 1 (XRCC1), as a DNA Repair protein from patients with the risk of age-related cataract at a Tertiary Care Centre, Uttar Pradesh.
 Material and methods: This was a case control study carried out in the Department of Anatomy & Department of Ophthalmology of RMCH&RC for a period of 2 year i.e., June 2020 to June 2022. A total of 500 clinical suspected cases were included in our study in which 250 patients were confirmed as cataract positive patients whereas 250 were the Controls. The Demographic profiles of the cases were recorded after duly obtaining consent. The 5ml of venous blood was collected in Ethylene diamine tetraacetic acid tubes.
 DNA was extracted by using Qiagen DNA Extraction kit as per manufactures guidelines. The AP endonuclease-1 (APE) and X-ray cross-complementing group 1 (XRCC1) gene was detected by the conventional PCR.
 Results: In the present study the maximum number of cases were reported in the Females as compared to the Males with the maximum age group of 51-60 years being affected the most. The Expression of (AP) –endonuclease (APE1) gene was more 68.4 % as compared to X-ray cross-complementing group 1 (XRCC1) with 62.8 %. The increase expression indicates the presence of these genes in the DNA repair damage.
 Conclusion: The Expression of (AP)-endonuclease (APE1) gene was more 68.4% as compared to X-ray cross-complementing group 1 (XRCC1) with 62.8%. The increase expression indicates the presence of these genes in the DNA repair damage. So, there should be early screening and its molecular detection of the DNA repair gene, which will help the clinician in the early diagnosis as well as early treatment of the cataract.

Molecular Characterisation of X-ray Cross-complementing Group 1 (XRCC1) Gene and Risk Factors in Senile Cataract Patients attending a Tertiary Care Hospital, Uttar Pradesh, India

Introduction: Cataract arises because of aging of the crystalline lens of the eye which prevents clear vision. X-ray Cross-complementing Group 1 (XRCC1) is a Deoxyribonucleic Acid (DNA) repair protein which is involved in Single-Strand Breaks (SSBs) and Base Excision Repair (BER) pathway which is responsible for the efficient repair of DNA damage is mainly responsible for cataract in patients. Aim: To study the prevalence, risk factors and the molecular characterisation with its special association to XRCC1 gene in senile cataract patients. Materials and Methods: This was a cross-sectional study carried out in the Department of Anatomy and Ophthalmology, Rama Medical College Hospital and Research Centre, Kanpur, Uttar Pradesh, India, from April 2021 to April 2022. A total of 500 clinical patients were included in which 250 patients were confirmed as cataract positive patients. Venous blood of 5 mL was collected in Ethylene diamine tetra-acetic acid tubes. The DNA extraction for the detection of XRCC1gene was done using Qiagen DNA extraction kit as per manufactures guidelines, which was further confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: A total of 500 clinically suspected patients were included in which 250 cases were confirmed as cataract positive patients. The ratio of females was more (n=130, 52%) compared to males (n=120, 48%) with the mean age for females with 57.6% and for males with 61.13%. Hypertension (n=173, 69.2%) was the most common disease associated with the cataract patients. The ratio of males were more (n=91, 75.8%) compared to females (n=82, 63.07%). The mean age of males was 64.40 years and that of females were 62.45 years. The other co-morbidity included diabetes (48.8%), in which males constituted 67 (55.83%) participants compared to the females with 55 (42.3%) participants. The presence of XRCC1 gene was detected in all cataract positive patients, which was also confirmed by RT-PCR. Conclusion: The polymorphisms of DNA repair genes decreased their ability to repair DNA damage, leaving human body a greatly increased susceptibility to cancer or agerelated diseases. The association of XRCC1 gene with agerelated cataract susceptibility observed in the present study supports the view that XRCC1 gene plays an important role in susceptibility to age-related cataract, so early screening and its molecular profiling will help the clinician in the early diagnosis as well as early treatment.

Glucose Increases STAT3 Activation, Promoting Sustained XRCC1 Expression and Increasing DNA Repair.

Dysregulation of DNA repair is a hallmark of cancer, though few cancer-specific mechanisms that drive the overexpression of DNA repair proteins are known. We previously identified STAT3 as a novel transcriptional regulator of X-ray cross-complementing group 1 (XRCC1), an essential scaffold protein in base excision repair in triple-negative breast cancers. We also identified an inducible response to IL-6 and epidermal growth factor stimulation in the non-tumorigenic embryonic kidney cell line HEK293T. As IL-6 and EGF signaling are growth and inflammatory-inducible responses, we examined if glucose challenge can increase STAT3 activation, promoting adaptive changes in XRCC1 expression in different cell types. Acute high glucose exposure promoted XRCC1 expression through STAT3 activation, increasing the repair of methyl methanesulfonate-induced DNA damage in HEK293T cells and the osteosarcoma cell line U2OS. Sustained exposure to high glucose promoted the overexpression of XRCC1, which can be reversed upon glucose restriction and down-regulation of STAT3 activation. Thus, we have identified a novel link between XRCC1 expression and STAT3 activation following exogenous exposures, which could play a critical role in dictating a cancer cell’s response to DNA-damaging agents.

Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer.

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

Polymorphism of XRCC1 Arg399Gln may predict for development of end-stage renal disease. A PCR confirmed case-control study

ObjectivesEvaluation of the frequency of X-ray Cross Complementing group 1 (XRCC1) Arg399Gln polymorphism among patients with end-stage renal disease (ESRD) patients and to determine if a possible association was present. Subjects & methodsBlood samples were obtained from 70 ESRD patients and 30 healthy volunteers as control group for routine laboratory investigations and genomic DNA was extracted using GeneJET Whole Blood DNA Purification Kit to detect XRCC1 codon 399 genotype Arg/Gln in exon 10. BCNL digestion resulted in two fragments of 389 and 121 bp for wild-type homozygous (Arg/Arg); one fragment of 510 bp for variant homozygous (Gln/Gln); and three fragments of 510, 389 and 121 bp for variant heterozygous (Arg/Gln). ResultsCompared to control subjects, ESRD patients showed significantly higher frequency of Arg/Gln genotype, but had significantly lower frequency of Arg/Arg genotype. Moreover, patients had significantly lower frequency of Arg allele in comparison to controls (57.1% vs. 83.3%, respectively). Furthermore, the frequency of recessive models; Gln/Gln + Arg/Gln was significantly higher, while the frequency of dominant models; Arg/Arg + Arg/Gln was non-significantly lower among patients than controls. Development of ESRD was positively correlated with the presence of XRCC1 Arg/Gln genotype, while was negatively correlated with the presence of XRCC1 Arg/Arg genotype. ROC curve analysis showed that presence of XRCC1 Arg/Arg genotype is a negative sensitive predictor, while XRCC1 Arg/Gln genotype is a positive significant predictor for development of ESRD and Regression analysis defined presence of XRCC1 Arg/Arg genotype as significant negative predictor for development of ESRD. ConclusionThe results of the current study indicated an intimate relation between XRCC1 gene polymorphism and development of ESRD and the predictive value of its presence for the possibility of progression of chronic kidney disease to ESRD stage.

Association between XRCC3 Thr241Met polymorphism and risk of gynecological malignancies: A meta-analysis

Studies have investigated the relationship between the X-ray cross- complementing group 3 (XRCC3) Thr241Met polymorphism and the risk of gynecological malignancies (GM) with the contradictory conclusions. Here, a meta-analysis was performed to provide clear picture of the association between Thr241Met and GM risk. The Pubmed and Chinese National Knowledge Infrastructure (CNKI) databases were searched for published eligible studies. The pooled odds ratios (OR) with their corresponding 95% confidence interval (CI) was used to assessed the strength of association. Totally, 15 publications with 5,740 cases and 9,931 controls were included. In the overall analysis, the results of meta-analysis showed no significant association between the Thr241Met and the risk of GM. However, in the Asians subgroup, significant increased risks were found in the comparisons of TT/CT+TT vs. CC(TT vs. CC: OR=3.25, 95% CI=1.47–7.18; CT+TT vs. CC: OR=1.51, 95%CI=1.10–2.09) in Asians; additionally, stratified analysis by cancer type in Asians, significantly increased risks was found in cervical carcinoma (CT vs. CC: OR=1.50, 95%CI=1.04–2.14; TT vs. CC: OR=3.14, 95%CI=1.38–7.14; CT+TT vs. CC: OR=1.64, 95% CI=1.17–2.31). It suggests that the risk of GM might be significantly increased by the XRCC3 Thr241Met polymorphism according to ethnicity and cancer types. Further studies with larger sample size in different ethnic populations and different sites of GM are needed to verify the findings.

Influence of Two DNA Repair Pathway Polymorphisms in Colorectal Cancer Risk in Southwest Iran.

Objective:X-ray cross-complementing group 1 (XRCC1) and 8 Oxo guanine DNA-glycosylase 1 (OGG1) genes are implicated in the repair of single-stranded breaks (SSBRs) and base excision repair (BER) pathways. Common polymorphisms in DNA repair genes are supposed to decrease the capability of DNA repair and cause genetic instability. This study was designed to investigate the association between XRCC1 (rs25487) and OGG1 (rs1052133) polymorphisms and susceptibility to colorectal cancer (CRC) in the Ahvaz city, south-west Iran. Methods:This case- control study comprised 150 patients and 150 controls that were selected from 2 educational hospitals in Ahvaz. They were matched for age and gender, and their genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results:Our results indicate that the frequency of the Gln (A) allele of XRCC1 (rs25487) is significantly higher in colorectal cancer patients, compare to controls (p = 0.01, OR: 1.54, 95% CI 1.9–13.3). Significant increased risk of cancer was observed in XRCC1 (rs25487) genotypes (p = 0.001 OR: 5.3, 95% CI 1.9–14.2 for Gln / Gln), while no association was found between OGG1 (rs1052133) and colorectal cancer risk (p = 0.6). Conclusion:Our study suggests that XRCC1 (rs25487) polymorphism might be associated with an increasing risk of CRC in Ahvaz. It also demonstrates positive correlation between the XRCC1 (rs25487) genotypes and demographic characteristics, such as smoking and increased age in patients and control groups.

The XRCC4 rs1805377 polymorphism is not associated with the risk of cancer: An updated meta-analysis.

ObjectivesA growing number of studies have reported that genes involved in the repair of DNA double-strand breaks might be cancer-susceptibility genes. The x-ray cross-complementing group 4 gene (XRCC4) encodes a protein that functions in the repair of DNA double-strand breaks, and this meta-analysis aimed to investigate the relationship between the XRCC4 rs1805377 polymorphism and cancer occurrence.MethodsWe retrieved case–control studies that met the inclusion criteria from PubMed, Web of Science, Embase, and China National Knowledge Infrastructure databases. Associations between rs1805377 and cancer risk were evaluated by odds ratios (ORs) using a random effects model and 95% confidence intervals (CIs) as well as sensitivity and subgroup analyses.ResultsAfter inclusion criteria were met, the meta-analysis involved 24 studies that included 9,633 cancer patients and 10,544 healthy controls. No significant association was found between rs1805377 and the risk of cancer (pooled OR = 1.107; 95% CI = 0.955–1.284) in the dominant genetic model. Similarly, no significant association was observed in the subgroup analysis.ConclusionsThrough this meta-analysis, we found no association between the rs1805377 polymorphism and cancer occurrence. This may provide useful information for relevant future studies into the etiology of cancer.

The single nucleotide polymorphism arg399gln rs25487 in XRCC1 gene is a breast cancer risk factor, but is not related to tp53 mutation status

Genetic changes in DNA repair genes, such as X-ray cross-complementing group1 (XRCC1), can cause modifications in the capacity of damaged DNA repair and affect the risk of cancer. Several mutations in TP53, which is a tumor suppressor gene, have been associated with breast cancer. In this study, it is aimed to evaluate the association of genetic variation in XRCC1rs25487 single nucleotide polymorphism (SNP) with TP53 mutation and breast cancer risk. In this research, 200 breast cancer women and 200 controls from the Iranian-Azeri population, Iran, were enrolled. Genomic DNA was extracted from the whole blood of controls patients. PCR-RFLP was carried out to genotype all participants for XRCC1rs25487SNP. Determination of possible mutations of TP53 in exons 5,6,7, and 8 were performed on 30 cancerous breast tissues through sequencing the amplified fragments. Our results of the case-control study indicated that the GA genotype of XRCC1 gene in rs25487polymorphism has a significantly risk effect on the breast cancer in the dominant genetic model (OR: 1.580, 95% CI: (1.025-2.436); p-value =0.049) and also GA genotype of XRCC1 gene in rs25487polymorphism has a protective effect on breast cancer in overdominant genetic model (OR: 0.591, 95% CI (0.395-0.886), p-value = 0.014). Furthermore, genotypes of this SNP did not associate with the clinical specifications of the patients and P53 mutation status. Sequencing results showed the mutational spectrum of P53 in the studied cases. According to the results of this study, in some of the genetic models, XRCC1SNP appears to be a modulator of breast cancer risk in Iranian East-Azerbaijan women. However, there was no correlation between XRCC1SNP and TP53 mutation status of the tumor.

Role of DNA repair genes XRCC3 and XRCC1 in predisposition to type 2 diabetes mellitus and diabetic nephropathy

IntroductionIncreasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methodsPolymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusionPolymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14–8.40 and OR 3.29 95% CI 1.23–8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population.

Role of DNA repair genes XRCC3 and XRCC1 in predisposition to type 2 diabetes mellitus and diabetic nephropathy

IntroductionIncreasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methodsPolymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusionPolymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14–8.40 and OR 3.29 95% CI 1.23–8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population.

Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers

Surniyantoro HNE, Lusiyanti Y, Rahardjo T, Nurhayati S, Tetriana D. 2018. Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers. Biodiversitas 19: 1676-1682. This study was aimed to examine the association between XRCC1 exon 10 gene polymorphism and micronucleus frequencies in radiation workers and their relation to the confounding factors. This study involved 37 radiation workers and 37 controls from several hospitals in Indonesia. Genotyping of X-ray cross-complementing group 1 (XRCC1) exon 10 gene polymorphism and micronucleus assay were performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Cytokinesis-Block Micronucleus assay (CBMN assay), respectively. The results indicated that MN frequencies were not significantly higher in the exposed workers than in controls (20.46±6.42 versus 16.89 ±9.72; P=0.07). The micronucleus frequencies of radiation workers with mutant genotype showed not significantly higher than controls in the same genotypes (22±6.64 versus 11.75 ± 8.13; P=0.11). The confounding factors, like age, years of employment and equivalent doses were significantly associated with micronucleus frequencies (P<0.05). The equivalent dose has a significantly positive correlation with micronucleus frequencies among radiation workers, increasing the MN frequencies by 16.3 per 1 mSv of equivalent dose (P=0.001). The genetic polymorphism of XRCC1 gene exon 10 demonstrated no association with the extent of DNA damage in the hospital radiation workers. The MN frequencies were strongly associated with age, equivalent dose and years of employment.

Association of X-ray cross-complementing group 3 Thr241Met gene polymorphism with osteosarcoma risk and its development and prognosis.

The relationship between X-ray cross-complementing group 3 (XRCC3) Thr241Met gene polymorphism and osteosarcoma risk and its development and prognosis is still debated. This meta-analysis was performed to assess these associations. The association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method. Interestingly, all the included studies were from Asian population. The meta-analysis indicated that XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk (T allele: Odds ratio [OR] =1.57, 95% confidence interval [CI]: 1.25-1.98, P = 0.0001; TT genotype: OR = 2.23, 95% CI: 1.40-3.57, P = 0.0008; CC genotype: OR = 0.69, 95% CI: 0.54-0.87, P = 0.002). However, XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis. XRCC3 Thr241Met gene polymorphism was associated with osteosarcoma risk, but XRCC3 Thr241Met CC genotype was not associated with Enneking stage, tumor location, and tumor metastasis.

Relationship Between Expression of Proteins ERCC1, ERCC2, and XRCC1 and Clinical Outcomes in Patients with Rectal Cancer Treated with FOLFOX-Based Preoperative Chemoradiotherapy.

Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1), and excision repair cross-complementing group 2 (ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT). Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes. Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [p<0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721-32.457]. Furthermore, a poor response to CRT (pathological TRG of 2-3) (p=0.18; OR 5.685; 95% CI 1.349-23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5ng/mL) (p=0.03; OR 6.288; 95% CI 1.198-33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients. ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs.

Genetic Polymorphisms of X-ray Repair Cross-Complementing Group 1 and Apurinic/Apyrimidinic Endonuclease-1 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease is interspersed with exacerbations; periods of acute symptomatic, physiological, and functional deterioration. The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms and the risk of COPD. Blood samples from 354 unrelated subject (age range 18-60years; 156 with COPD, 198 healthy controls) were collected. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Asp148Glu using a confronting two pair primers polymerase chain reaction. GA genotype of XRCC1 gene was found to be predominant in the COPD group compared to controls with 1.86-fold increased risk for COPD (OR 1.86, 95% CI 1.20-2.88, p = 0.0013). TG genotype of APE1 was found to be predominant in COPD group compared to controls with the difference being statistically significant (OR 1.68, 95% CI 1.08-2.61, p = 0.0043). The GA haplotype was found to be predominant in COPD than controls with a 2.19-fold significant increase (OR 2.19, 95% CI 1.46-3.28, p = 0.003). Polymorphism in XRCC1 and APE1 gene is associated with an increased risk of COPD.

Association Between X-Ray Cross-complementing Group 3 (XRCC3) Thr241Met Polymorphism and Risk of Thyroid Cancer: A Meta-Analysis.

BackgroundThe X-ray cross-complementing group 3 (XRCC3) gene encodes a protein that plays an important role in homologous recombination repair (HRR) of DNA double-strand break (DSB). Increasing attention has been drawn to the association of XRCC3 T241M polymorphism with various types of human cancers. In this study, a meta-analysis was performed to investigate whether there is an association between XRCC3 T241M polymorphism and thyroid cancer risk.Material/MethodsA comprehensive search was conducted and a total of 8 studies that covered 963 thyroid cancer cases and 1942 controls were included in this analysis. The meta-analysis was performed on both overall database and 2 ethnic subgroups (Caucasian and Asian). The fixed-effects model was used to calculate odds ratio (OR) with 95% confidence intervals (CIs). The publication bias was evaluated using Begg’s funnel plots and Egger’s test.ResultsA positive association between XRCC3 T241M polymorphism and thyroid cancer risk was found by the analyses of the overall database using both recessive model (OR=1.40, 95% CI=1.08–1.81, P=0.012) and homozygote comparison (OR=1.41, 95% CI=1.07–1.86, P=0.015), but not by that using the dominant model (OR=1.12, 95% CI=0.95–1.33, P=0.18). However, no significant association of XRCC3 Thr241Met polymorphism with the risk of thyroid cancer was found in individual ethnic subgroups.ConclusionsWe conclude that the XRCC3 Thr241Met polymorphism is associated with an increased risk of thyroid cancer in the overall population, while no significant association was observed in individual ethnic subgroups due to limited population size.

Susceptibility to Breast Cancer and Intron 3 Ins/Del Genetic Polymorphism of DNA Double-Strand Break Repair Gene XRCC4.

SummaryBackgroundSince genetic variations in X-ray cross-complementing group 4 (XRCC4; OMIM: 194363) repair gene might be associated with a reduction in cellular DNA repair capacity, it is hypothesized that XRCC4 Ins/Del (I/D) polymorphism (in intron 3 of the gene; rs28360071) may be a risk factor for breast cancer. Therefore, the present case-control study was carried out.MethodsThe present case-control study included 407 females with breast cancer and a total of 394 healthy females from the general population matched with patients according to age. Genotypic analysis for the XRCC4 I/D polymorphism was performed by PCR. In order to investigate the effect of XRCC4 I/D polymorphism on age at diagnosis of breast cancer, the Kaplan–Meier survival analysis and the Cox proportional hazards regression model were used.ResultsBased on the present case-control study, the ID (OR=0.95, 95% CI: 0.69–1.31, P=0.781) and DD (OR=1.24, 95% CI: 0.84–1.83, P=0.274) genotypes were not associated with breast cancer risk compared with the II genotype. Based on the Cox regression model, there was significant association between genotypes of I/D polymorphism and age at diagnosis of breast cancer (ID+DD vs II; HR=0.79, 95% CI: 0.64–0.98, P=0.036).ConclusionAlthough there was no significant association between XRCC4 I/D polymorphism and risk of breast cancer, patients having the II genotype have lower age at diagnosis in comparison with patients having ID+DD genotypes.

DNA repair gene ERCC1 C118T polymorphism predicts sensitivity of recurrent esophageal cancer to radiochemotherapy in a Chinese population

BackgroundDNA repair gene polymorphisms could alter DNA repair capacity and therefore associate with tumor sensitivity to radiochemotherapy. This study assessed excision repair cross-complementing group 1 (ERCC1) C118T and X-ray cross-complementing group 1 (XRCC1) G399A single-nucleotide polymorphisms in esophageal patients for an association with sensitivity to radiation and chemotherapy.MethodsEsophageal squamous cell carcinoma patients (n = 118) who relapsed after surgery were enrolled for assessment of ERCC1 C118T and XRCC1 G399A polymorphisms by direct DNA sequencing.ResultsThe response rate of treatments was 48.30%: 14 complete response (CR, 11.86%), 43 partial response (PR, 36.44%), 49 stable disease (SD, 41.53%), and 12 progressive disease (PD, 10.17%). ERCC1 C118T was significantly associated with treatment response (C/T vs. C/C + T/T, odds ratio [OR] = 6.035, 95% confidence interval [CI]: 2.114–17.226, P = 0.001) after adjusting for other clinicopathological factors. Patients carrying the C/T genotype had significantly prolonged overall survival (OS) compared with C/C and T/T (median OS 43.00 vs. 27.00, P = 0.027). Multivariate Cox regression showed that a response was only an independent prognostic factor for OS (CR + PR vs. SD+PD, HR = 0.471 95% CI 0.269–0.826, P = 0.009). Grade III and IV adverse events occurred in 12 of 118 patients (10.17%). Only concurrent radiochemotherapy significantly increased these adverse events (OR = 26.529, 95% CI 2.312–304.389, P = 0.008).ConclusionERCC1 C118T could be a predictive factor for the response to radiotherapy and chemotherapy, but not a prognostic factor for OS in esophageal cancer patients after surgery.

Allelic prevalence of intron 3 insertion/deletion genetic polymorphism of DNA double-strand break repair gene XRCC4 in four healthy Iranian populations

Background and purposeThe X-ray cross-complementing group 4 (XRCC4; OMIM: 194363), plays an important role in repair of DNA double-strand breaks via non-homologous end joining pathway. In order to find the allelic prevalence of an insertion/deletion polymorphism in intron 3 of XRCC4 (Ins/Del; rs28360071) among Iranian populations, the present study was carried out. Subjects and methodsThe total study subjects consisted of 662, 200, 291, and 200 individuals from Shiraz (Fars province; belong to Persians), Abarku (Yazd province; belong to Persians), Tabriz (East Azerbaijan province; belong to Azaris), and Yasuj (Kohgiluyeh va Boyer-Ahmad province; belong to Lurs), respectively. Genotypic analysis of the Ins/Del XRCC4 polymorphism was detected by the PCR method. ResultsThe prevalence of the Del allele in Shiraz, Abarku, Tabriz, and Yasuj was estimated 44.4%, 37.3%, 53.6% and 45.0%, respectively. Tabriz (Azaris) showed the significant difference with other populations (χ2=20.06, df=1, P<0.001). Also there was a significant difference between Persians of Shiraz and Abarku (χ2=6.43, df=1, P=0.011). ConclusionAlthough there is a significant heterogeneity between Iranian populations, the Del allele shows high prevalence among Iranian populations, which is much higher than the allelic prevalence among Asians.

DNA repair gene XRCC3 variants are associated with susceptibility to glioma in a Chinese population.

The susceptibility to glioma is not well understood. It has been suggested that the X-ray cross complementing group 3 (XRCC3) gene influences the capacity to repair DNA damage, leading to increased glioma susceptibility. In this study, we evaluated the relationship between XRCC3 mutations and glioma risk. Genotypes were assessed in 389 Chinese glioma patients and 358 healthy controls. XRCC3 Thr241Met (rs861539) and 2 additional polymorphisms, rs3212112 (c.774+19T>G) and rs1799796 (c.562-14A>G), were directly sequenced. The frequency of the rs861539 T allele was significantly lower in the glioma group than in healthy controls [11.1 vs 17.7%, odds ratio = 0.62 (0.48-0.80), P < 0.001]; the frequencies of the CT or CT+TT genotypes differed between groups (18.5 vs 31%, 20.3 vs 33.2%, respectively). The frequency of the rs3212112 G allele was significantly higher in the glioma group than in healthy controls [15.8 vs 5.3%, odds ratio = 2.94 (2.07-4.17), P < 0.001]. The frequencies of the GT or TG+GG genotypes differed between groups (25.4 vs 7.8%, 28.5 vs 9.2%, respectively). This study demonstrates that the rs861539 and rs3212112 polymorphisms in the XRCC3 gene may influence the risk of glioma development in Chinese populations.