Arg399Gln Polymorphism Research Articles

Abstract B034: Polymorphisms in XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair genes elevate cervical cancer risk among Bangladeshi female population

Abstract Introduction and Objective: Cervical cancer is the second most common cancer in women worldwide and is both a preventable and a curable disease especially if identified at an early stage. Sequence variations in DNA repair genes can cause aberration in cellular functions leading to cancer. Genetic polymorphisms in XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) genes result in individual variation in their DNA repair capacity. The aim of this study was to identify the association between XRCC1 Arg399Gln and XRCC3 Thr241Met single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer in Bangladeshi populations. Methods: The case-control study comprised 124 cervical cancer patients and 148 healthy controls. Genomic DNAs were isolated from peripheral blood and genotyped for candidate SNPs using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Results: For XRCC1, heterozygous Arg/Gln and combined heterozygous plus variant homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0037 to 2.8771, p=0.0484) and 1.8627-fold (95% CI 1.1470 to 3.0250, p = 0.0119) increased risk of cervical cancer, respectively, when compared with normal homozygous Arg/Arg genotype. The variant Gln allele was positively associated with cervical cancer by 1.68-fold increase (95% CI 1.1732 to 2.3980, p = 0.0046). Similarly, for XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were found to be associated with 1.6993-fold (95% CI 1.0398 to 3.0166, p=0.0354) and 1.8312-fold (95% CI 1.0890 to 3.0791, p = 0.0225) higher risk, respectively, when compared with normal homozygous Thr/Thr genotypes. The variant Met allele showed significant association with 1.71-fold increased risk. Conclusion: XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased cervical cancer risk in Bangladeshi females. Citation Format: Md. Mustafizur Rahman, Laboni Das, Sadia Rahman, Amir Hossain, Razia Sultana. Polymorphisms in XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair genes elevate cervical cancer risk among Bangladeshi female population [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B034.

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.

The Relationship between Gene Polymorphisms od the XRCC1 and TP53 with the Gender of Children with Acute Leukemia.

The relevance of the study lies in the fact that although the role of polymorphism of some genes that are responsible for cell apoptosis and deoxyribonucleic acid repair in the development of acute leukemia has already been established, its relationship with the gender of patients has not been studied enough. This study was aimed at studying the relationship between the Arg399Gln polymorphism in the XRCC1 deoxyribonucleic acid repair gene and the Arg72Pro polymorphism in the TP53 tumor suppressor gene encoding the p53 protein with the gender of children with acute leukemia. The study included 100 newly diagnosed pediatric patients of Kyrgyz nationality (69 boys and 31 girls), among which there were 77 patients with acute lymphoblastic leukemia, 22 patients with acute myeloblastic leukemia and 1 patient with a biphenotypic variant. Determination of polymorphisms was carried out by PCR-RFLP analysis or polymerase chain reaction followed by an analysis of restriction fragment length polymorphism. The interrelation of the results obtained with the patients' gender was assessed using statistical methods. The study showed that there were no gender differences for all three genotypes of the Arg72Pro polymorphic marker of the tumor suppressor p53 (ТР53). Three Arg399Gln genotypes of the XRCC1 gene also did not depend on gender. However, with a separate analysis of each polymorphism, there was a tendency for a greater proportion of the Arg/Gln genotype in the group of boys compared to girls. The Gln/Gln polymorphism relationship requires further study due to insufficient data for analysis. The study has expanded the understanding of genetic changes and their relationship with gender, which have diagnostic, prognostic and therapeutic implications in acute leukemia. The conducted research of the relationship between individual phenotypes of acute lymphoblastic leukemia with risky polymorphisms in some genes contributes to the study of AL.

Association between single nucleotide polymorphisms in DNA repair genes and the efficacy of radiotherapy in nasopharyngeal carcinoma patients.

Single nucleotide polymorphisms (SNPs) in DNA repair genes are mainly correlated with the response to radiotherapy in nasopharyngeal cancer (NPC). In NPC patients, previous research has studied the association between X-ray repair cross-complementing group 1 and 3 (XRCC1 and XRCC3) polymorphisms and radio-therapeutic response. The objective of our study was to test the association between XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms and the response to radiotherapy in the NPC Moroccan population. A total of 100 patients with NPC were genotyped for polymorphisms in XRCC1 and XRCC3 genes. The results revealed that the genotypes and alleles of both SNPs did not show any significant association with clinical stages (for XRCC1 Arg399Gln: p [genotype] = 0.559; p [allele] = 0.440) and (for XRCC3 Thr241Met: p [genotype] = 0.638; p [allele] = 0.567). Moreover, in the study of the association between the polymorphisms and radiotherapy, the response to radiation therapy between genotypes and alleles was not statistically significant (for XRCC1 Arg399Gln p [genotype] = 0.583; p [allele] = 0.459) and (for XRCC3 Thr241Met p [genotype] = 0.660; p [allele] = 0.590). The present study suggests that XRCC1 Arg399Gln polymorphism does not have any impact on the radio-therapeutic response in Moroccan NPC patients whereas XRCC3 Thr241Met polymorphism may act as a prognostic indicator for NPC patients treated with radiotherapy. However, studies with a larger sample are needed to confirm our results.

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review.

Head and neck squamous cell carcinomas (HNSCCs) are associated with variable prognosis even with similar clinical characteristics and treatments. Gene polymorphisms have been suggested as prognostic factors for HNSCC which can justified this variable prognosis. So, the aim was to review literatures on gene polymorphisms and prognosis of HNSCCs. A systematic search was conducted using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases to find all related articles published up to December 2021 in the field of gene polymorphisms and HNSCC prognosis. Of 1029 initial searched articles, 71 articles were selected for inclusion in this systematic review. About 93 genes and 204 polymorphisms have been discussed in these articles. Among the most studied polymorphisms, the XRCC1 Arg399Gln and Arg194Trp polymorphisms were not associated with survival in most studies; the ERCC1 C19007T polymorphism had no significant association in any of the studies. Different gene polymorphisms of glutathione s-transferase family, including GSTM1 deletion, GSTT1 deletion and GSTP1 A313G, were not associated with survival in included studies. There are conflicting results regarding the association between polymorphisms such as ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. Less studied polymorphisms, such as hOGG1 rs1052133 or the VEGF rs699947, were generally not associated with HNSCC prognosis. Reviewed articles reported varied and contradictory results regarding the association of gene polymorphisms and HNSCC prognosis, which necessitates further studies along with meta-analysis on the results of such studies.

Genetic polymorphisms in DNA repair genes and their association with risk of cervical cancer: A systematic review and meta-analysis.

There have been a large number of epidemiologic studies regarding the association between genetic polymorphisms in DNA repair genes and onset of cervical cancer. However, results are inconsistent. Articles published before June 2021 and regarding genetic polymorphisms in DNA repair genes and cervical cancer were searched in following databases: PubMed, Web of Science, Google Scholar, and CNKI. With at least three articles for each polymorphism, we made meta-analysis to compute multivariate odds ratios (ORs) and their 95% confidence intervals (CIs). The present study showed significant associations between XRCC1 Arg399Gln polymorphisms and risk of cervical cancer in Asian, whereas no significant association between them were showed in Caucasian (Asian: GA vs. GG: OR = 1.27, 95%CI 1.06-1.52; AA vs. GG: OR = 1.91, 95%CI 1.29-2.83; GA + AA vs. GG: OR = 1.36, 95%CI 1.12-1.65; AA vs. GG + GA: OR = 1.66, 95%CI 1.17-2.37; Caucasian: GA vs. GG: OR = 1.08, 95%CI 0.83-1.41; AA vs. GG: OR = 2.18, 95%CI 0.75-6.31; GA + AA vs. GG: OR = 1.23, 95%CI 0.85-1.78; AA vs. GG + GA: OR = 1.70, 95%CI 0.69-4.18). In addition, there were significant associations between ERCC2 rs13181 polymorphisms and risk of cervical cancer in Asian (AC vs AA: OR = 0.53, 95%CI 0.37-0.75, I2 = 0.0%, p value of Q test = 0.847; AC + CC vs AA: OR = 0.50, 95%CI 0.36-0.70, I2 = 0.0%, p value of Q test = 0.856). The meta-analysis showed that there were significant associations between XRCC1 Arg399Gln and ERCC2 rs13181 polymorphisms and risk of cervical cancer.

A Prognostic Model Based on XRCC1 Gene Polymorphisms and Clinicopathological Factors to Predict One-Year Survival of Advanced Epithelial Ovarian Cancer Patients

Prognosis of advanced stage epithelial ovarian cancer (EOC) patients remains poor due to recurrence and disease progression after surgery and chemotherapy. Polymorphism in the genes involved in DNA repair, i.e. x-ray repair cross complementing protein-1 (XRCC1) and XRCC3 could alter function, diminish repair kinetics and may play a role in tumor resistance to therapy. This study was aimed to predict the prognosis of advanced stage EOC patients based on the polymorphism of XRCC1 and XRCC3 genes and the clinicopathology. This was an ambispective cohort study in EOC patients treated in Fatmawati General Central Hospital and its network hospitals in Jakarta between 2011 and 2016. Demographic data and clinicopathology was obtained from the medical record. Polymorphisms of XRCC1 and XRCC3 genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Survival analyses were performed using the Kaplan-Meier curve and Cox proportional hazard test. Multivariate analyses were performed to obtain prediction model for 1-year survival. Scoring system was developed and tested using the receiver operating characteristic (ROC) curve analyses. A total of 129 eligible cases were included. Patients’ mean age was 49.6 years. Most patients (93.8%) were having stage III disease. Mortality at 1-year was associated with three independent variables, i.e. histopathology subtype, residual tumor > 1 cm, and XRCC1 gene Arg399Gln polymorphisms (Arg/Gln or Gln/Gln alleles). These prediction models gave 85.3% accuracy by ROC curve analysis and 82.7% posttest probability. Prognosis of advanced stage EOC patients can be predicted from several clinicopathological factors and XRCC1 gene polymorphisms. Validation study is needed to confirm these findings.

Association Between X-Ray Repair Cross-Complementing Group 1 Arg399Gln Polymorphism and Risk of Oral Leukoplakia: A Meta-analysis.

Aims: Previous studies have have reported inconsistent results regarding the association of the XRCC1 polymorphism Arg399Gln with oral leukoplakia (OLK) risk. This study was designed to assess the existing evidence of this association using a meta-analytic approach. Materials and Methods: The literature was searched using multiple databases, including PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), through October 22, 2020. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Results: A total of 671 Indian cases and 1009 Indian controls from seven case-control studies were included in the meta-analysis. The overall analysis revealed that the AA genotype was associated with a significantly increased OLK risk compared with the GG+GA genotypes (OR = 1.51, 95% CI = 1.10-2.06). In the subgroup analysis stratified by tobacco use, a significant association was found in the mixed group (OR = 1.51, 95% CI = 1.12-2.56), but not in the tobacco-using group or the no tobacco use group. In the OLK subtype subgroup analysis, a significantly increased risk was found in the hyperplastic subgroup (OR = 5.01, 95% CI = 1.39-18.11), whereas no associations were found in the dysplastic or mixed subgroups. Conclusions: The results of this meta-analysis suggest that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility to OLK in the Indian population.

Influence of Arg399Gln, Arg280His and Arg194Trp XRCC1 gene polymorphisms of Base Excision Repair pathway on the level of 8-oxo-guanine and risk of head and neck cancer in the Polish population.

Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. In this work we investigate influence of three selected polymorphisms of DNA repair gene XRCC1 and level of oxidative damage (measured as level of 8-oxo-guanine) on modulation of the risk of HNSCC. In group of 359 patients with HNSCC (diagnosed with OSCC) the occurrence of polymorphic variants in Arg399Gln, Arg280His and Arg194Trp of XRCC1 were studied with TaqMan technique. In addition we determined level of 8-oxo-guanine with ELISA. Arg399Gln polymorphism and Arg194Trp polymorphism of XRCC1 gene increases the risk of HNSCC. The coexistence of Arg399Gln and Arg194Trp simultaneously enhances this effect. At the same time, their coexistence with His280His raises the risk to a level higher than in the absence of such coexistence, although the His280His itself is not associated with an increased risk of HNSCC. Patients have higher levels of 8-oxo-guanine than control group, and His280His is polymorphism with highest mean value of 8-oxoG level among studied. Patients with HNSCC not only have an increased level of 8-oxoguanine and the Arg399Gln and Arg/Trp of XRCC1 modulate risk of cancer, but there is also a relationship between these two phenomena, and it can be explained using intragenic combinations revealing that a high level of 8-oxoG could be a potential mechanism behind the modulation of HNSCC risk by the polymorphisms studied.

Age- and Gender-Independent Association of XRCC1 Arg399Gln Polymorphism with Chronic Myeloid Leukemia.

PurposeDNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population.Patients and MethodsThe present study was conducted on 186 newly diagnosed patients with CML, aged 19–70 years (118 males and 68 females; mean age of 46.15±13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94±8.97 years). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms.ResultsThe genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms.ConclusionXRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.

Cytokinesis-block micronucleus cytome (CBMN-CYT) assay and its relationship with genetic polymorphisms in welders

Fumes generated in the welding process are composed of micrometric and nanometric particles that form when metal fumes condense. The International Agency for Research on Cancer established that many compounds derived from the welding process are carcinogenic to humans. Still, there are few studies related to the role of genetic polymorphisms. This work aimed to analyze the influence of OGG1 Ser326Cys, XRCC1 Arg280His, XRCC1 Arg194Thr, XRCC1 Arg399Gln, XRCC3 Thr241Met, GSTM1, and GSTT1 gene polymorphisms on DNA damage of 98 subjects occupationally exposed to welding fumes and 100 non exposed individuals. The results showed that individuals exposed to welding fumes with XRCC3 Thr241Thr, XRCC3 Thr241Met, and GSTM1 null genotypes demonstrated a significantly higher micronucleus frequency in lymphocytes. In contrast, individuals with XRCC1 Arg399Gln and XRCC1 Gln399Gln genotypes had significant levels of NPBs. OGG1 326 Ser/Cys, OGG1 326 Cys/Cys, XRCC1 194Arg/Thr, XRCC1 194Thr/Thr, and GSTT1 null genotypes exhibited significantly higher apoptotic values. Also, XRCC1 194Arg/Trp, XRCC1 194Thr/Thr, and GSTM1 null genotype carriers had higher necrotic levels compared to XRCC1 194Arg/Arg and GSTM1 nonnull carriers. Compositional analysis revealed the presence of iron, manganese, silicon as well as particles smaller than 2 μm that adhere to each other and form agglomerates. These results may be associated with a mixture of components, such as nitrogen dioxide, carbon monoxide, and metallic fumes, leading to significant DNA damage and cell death processes. These findings demonstrated the importance of the association between individual susceptibility and DNA damage levels due to occupational exposure to welding fumes; and constitute one of the first studies carried out in exposed workers from Colombia.

Impact of ERCC2 Lys751Gln (rs13181), ERCC2 Asp312Asn (rs1799793) and XRCC1 Arg399Gln (rs25487) polymorphisms on the risk of prostate cancer among cases from the central region of Saudi Arabia

This study was undertaken to investigate an association between genetic variants of ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) or XRCC1 (Arg399Gln) polymorphisms with the risk of prostate cancer (PC) in Saudi population. This is a case-control study conducted on 124 PC patients and 425 healthy human controls. Blood samples were used for DNA extraction and gene polymorphisms for ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln). The risk of the associations was calculated by odds ratio (OR) and 95% confidence interval (CI). The data demonstrated no significant associations between ERCC2 (Lys751Gln) polymorphism and PC risk, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms were found to be significantly associated with PC risk (OR of 2.2, 95% CI, 1.1–4.1; p = 0.02) and (OR of 2.4, 95% CI, 1.3–4.5; p = 0.005), respectively. Likewise, recessive genotype models also showed significant association of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms with PC risk (p = 0.009). Interestingly, these genetic associations were more pronounced in aged populations (p = 0.003) as well as in smokers (p < 0.0001). Combination of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) genotypes showed strong association with the risk of PC onset (p < 0.001). These novel findings indicate that ERCC2 (Lys751Gln) polymorphism was not associated with risk of PC, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms showed strongly associated with the increased risk of PC. Combination of ERCC2 (Asp312Asn) and XRCC1 (Arg399 Gln) genotypes also showed strong association with increased risk of PC. In addition, more risk of PC onset was noticed in aged population and for those who were reported to have smoking history.

A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer.

Background:We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods:We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results:A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions:Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population. Further well-designed investigations with large sample sizes are required to confirm our results.

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.

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 of X-ray Repair Cross-Complementing Group 1 Arg399gln Polymorphisms with the Susceptibility to Develop Oral Squamous Cell Carcinoma in Tamol Chewer's Population in Assam, India

Background: Various environmental factors have been reported to play key role in the development of oral squamous cell carcinoma (OSCC). A lesser known risk factor of oral cancer in India is the uncontrolled use of areca nut chewing. In North-East India, Areca nut, locally called as “Tamol” in Assam, is raw betel nut, lime and betel leaf without tobacco, which are more effective as compared to dried which can be the important contributing factor for OSCC. Objectives: The aim of the study was to detect the association between XRCC1 polymorphisms and increased risk of OSCC in tamol chewers population in Assam, India. Methods: 50 OSCC patients, 50 tamol chewers and 50 controls were enrolled in the study. XRCC1 Arg399Gln polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: There was a significant association for XRCC1 codon 399 (Arg/Gln+Gln/Gln) (p&lt;0.05; OR=1.909, CI= 0.8622- 4.227) with the wild type in cancer sample as compared with control sample. Similarly, the positive association for 399G/G (p&lt;0.05; OR =2.842, CI = 0.919-8.79) genotypes with oral carcinoma and control sample. In case of tamol chewers, the AA genotype was found to be associated with 2-fold (OR- 2.25, CI= 0.709-7.14) increase risk of developing oral cancer while GA+AA genotype was associated with one and half fold (OR-1.62, CI=0.7354- 3.568) risk of developing oral cancer. Conclusions: Based on these results, the XRCC1399G&gt;A genotype could be used as a useful molecular biomarker to predict genetic susceptibility in tamol chewers population and its susceptibility to develop OSCC.

Genetic polymorphisms of base excision repair gene XRCC1 and susceptibility to benzene among employees of chemical industries

Benzene is the most dangerous combination of volatile organic compounds (VOCs) due to its carcinogenicity and toxic effects on the blood system. Benzene toxicity is rooted in its metabolism. This material can break the DNA and cause some changes in the base sequence. The XRCC1 gene plays an important role in repairing the damaged base since the polymorphisms of gene XRCC1 (rs1799782) and (rs25487), which lead to an increased risk of various cancers, are common. In this study, the association between the mentioned polymorphisms and the risk of individuals' vulnerability to benzene was investigated in a group of people exposed to benzene in an Iranian context. One hundred thirty-eight subjects suffering from blood disorders (case group) and 168 subjects without any blood disorder (control group) were evaluated. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphism detection. The results showed that XRCC1 Arg194Trp and Arg399Gln polymorphisms had no significant association with susceptibility to benzene. Similarly, Arg399Gln and Arg194Trp genotypes did not have any significant relationship with hematological parameters. The obtained results indicated that the distribution of genotypes was in Hardy-Weinberg equilibrium in both groups. Different geographic locations, population size, and different genetic backgrounds might probably have affected the results.

Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events.

Gastric cancer (GC) is a multistep process characterized by a gradual accumulation of genetic and epigenetic alterations in genes at various stages of progression. Epigenetic alterations like DNA methylation play an important role in cancer and may serve as a biomarker for cancer. The present study was aimed to investigate the promoter hypermethylation, expression profile, and Arg399Gln gene polymorphism of DNA repair gene XRCC1 (X-ray repair cross complimentary group I) in GC patients. A total of 60 histopathologically confirmed GC subjects were recruited in the study. Information on various dietary, lifestyle and environmental factors was obtained in face-to-face interviews using a structured questionnaire from each subject. Tissue samples were taken along with adjacent non-cancerous tissues for analysis. Promoter methylation status and expression of XRCC1 gene was evaluated using MS-PCR and western blotting respectively; while as Arg399Gln polymorphism was analyzed by PCR-RFLP. We found that the XRCC1 gene promoter of 38.3% cancerous tissues were methylated compared to 13.3% of adjacent normal tissues. The promoter hypermethylation status of the gene was found to be significantly associated with the loss of protein expression (P < 0.0001, OR = 14.63; 95% CI 4.01-53.43). However, we did not find any significant association of polymorphism of XRCC1 Arg399Gln with promoter methylation or protein expression. Further, comparison of methylation status and protein expression with clinical parameters like age, smoking status, etc. was also not significant (P > 0.05). The present study indicates that XRCC1 undergoes aberrant promoter hypermethylation with subsequent loss of protein expression in gastric cancer.

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.