X-ray Repair Cross-complementing Group Research Articles

Study on the Association of XRCC1 Gene rs72484243 Polymorphisms with Increased Laryngeal Cancer Risk

Objective: To study the association of X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with increased laryngeal cancer risk. Methods: A total of 120 individuals, comprising 60 patients with laryngeal squamous cell carcinoma (LSCC), and 60 healthy volunteers participated were selected. Blood samples were taken and analyzed, and 4 XRCC1 polymorphisms (rs145135970, rs1799780, rs25489, and rs72484243) were genotyped. Results: Gender, age, body mass index (BMI), and smoking habits were shown to be the high-risk factors for LSCC. Genotype and allele distributions for the 4 polymorphisms differed significantly between both groups (P < 0.05). Furthermore, carriers with the rs72484243GTGT- allele exhibited an increased risk of LSCC relative to those who had the rs145135970 GTGTGTGTGTGTGT- allele, the rs1799780 G-A allele, or the rs25489 C-T allele, as determined by binary logistic regression analysis (OR = 2.74, 95% CI: 1.27–5.91, P = 0.01), after accounting for possible co-factors like sex, age, BMI, drinking and smoking behavior, and special diet requirements. In addition, a TA haplotype and a GTGTGTGTGTGTGTTG haplotype were linked to LSCC in Chinese populations in a haploid association study of 4 SNP loci in the XRCC1 gene (P = 0.05 OR = 1.36, 95% CI = 1.1228–1.6406). Conclusion: Genetic polymorphisms of the XRCC1 gene at the rs72484243 site were correlated with an elevated risk of LSCC among the Xinjiang population.

Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.

The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.

Association of XRCC1 p. Arg194Trp gene polymorphism with the risk of hepatocellular carcinoma in HCV Egyptian population: A pilot case-control study.

Background: Hepatocellular carcinoma (HCC) is the most common and fatal primary liver cancer. Genetic variants of DNA repair systems can reduce DNA repair capability and increase HCC risk. Objectives: This study aimed to examine, in Egyptian hepatitis C virus (HCV) patients, the relationship between the X-ray repair cross-complementing group 1 (XRCC1) rs1799782 single nucleotide polymorphism (SNP) and HCC susceptibility. Methods: We included 100 adult HCV-positive patients with HCC and 100 adult HCV-positive patients with liver cirrhosis as pathological controls. XRCC1 rs1799782 SNP genotyping was done in both groups using quantitative real-time PCR (qPCR). The distribution of genotypes in patients and controls was compared using several inheritance models. Results: We found that the CT genotype, when analyzed under both the co-dominant (OR (95 % CI): 2.147 (1.184-3.893), p = .012) and the over-dominant (OR (95 % CI): 2.055 (1.153-3.660), p = .015) models, as well as the combined CT and TT genotypes under the dominant model (OR (95 % CI) of 1.991 (1.133-3.497), p = .017), were associated with increased susceptibility to HCC. The frequency of the T allele was higher among HCC participants (32%) compared to those with cirrhosis (23.5%) and carrying the T allele increased the risk of HCC by 1.532 times, however, these associations did not reach statistical significance (p-values >0.05). Moreover, the variant T allele was associated with worse clinical manifestations and laboratory results among the HCC group, but AFP levels were not affected significantly. Conclusions: Egyptians with XRCC1 rs1799782 SNP may have a higher risk of HCV-related HCC. More extensive multi-center prospective investigations must confirm this association.

XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis.

X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking. To address this knowledge gap, we conducted a systematic investigation employing bioinformatics techniques across 33 cancer types. Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases. Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, we observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, our findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy.

Lack of association between XRCC1 SNPs and acute radiation‑induced injury or prognosis in patients with nasopharyngeal carcinoma.

The response to radiation therapy (RT) is closely associated with DNA damage repair. X-ray repair cross-complementing group-1 (XRCC1) is a key gene in the DNA damage repair pathway, and SNPs in this gene alter the expression and activity of its effector protein, which may in turn affect sensitivity to RT. Therefore, the course of tumor treatment and local control rate can be influenced. In the present study, a group of 158 patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated RT at Fujian Cancer Hospital (Fuzhou, China) between July 2012 and October 2013 were included in retrospective chart review and followed up. Plasma was collected before treatment for genotype analysis of the three SNPs of XRCC1, namely Arg194Trp, Arg280His and Arg399Gln. Acute radiation-induced injuries sustained during treatment was graded according to the Radiation Therapy Oncology Group scoring criteria. Post-treatment follow-up was performed until August 2020. In the 158 cases of NPC, no statistically significant association was observed between the three SNPs of the XRCC1 gene and the severity of acute radiation-induced injury or prognosis. However, the AA genotype of XRCC1-Arg399Gln tended to be associated with worse progression-free survival (PFS) compared with the GA + GG genotype, although this was not significant (P=0.069). In addition, multivariate logistic analysis showed that nodal stage was significantly associated with the occurrence of acute severe radiation-induced oral mucositis (P=0.018), and there was also a trend towards an association between nodal stage and the incidence of acute severe radiation-induced pharyngitis; however, this was not statistically significant (P=0.061). Furthermore, multivariate Cox regression analysis showed that older age, distant metastasis and higher clinical stage were independent risk factors for PFS in patients with NPC. In conclusion, relying solely on the aforementioned SNPs of the XRCC1 gene may not provide a robust enough basis to predict the response to RT or prognosis in patients with NPC.

Impact of XRCC3 rs861539 and XPD rs13181 gene polymorphisms on childhood acute lymphoblastic leukemia in Egyptian patients

Abstract Background There is mounting evidence that the genotypes of DNA repair proteins and susceptibility to certain malignancies are related. Few studies, however, have examined the role of the homologous repair gene X-ray repair cross-complementing group 3 (XRCC3) genotype and xeroderma pigmentosum complementation group D (XPD) in the development or prognosis of acute lymphoblastic leukaemia (ALL). Aim of the study In this study, we investigated the impact of XRCC3 rs861539 and XPD rs13181 polymorphisms on the risk of ALL. To the best of our knowledge, this is the first report of XRCC3 and XPD polymorphisms in ALL Egyptian patients. Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to analyse XRCC3 rs861539 and XPD rs13181 gene polymorphisms in 96 patients with ALL and in 103 disease-free controls, who were of a similar age. Results ALL risk is lower in individuals with the homozygous variant TT genotype at XRCC3 rs861539. The heterozygous variant CT genotype of XRCC3 was connected to increased disease risk of ALL in males. Additionally, C allele frequency was noticeably higher than T allele frequency in pre B ALL. In this investigation, there was no correlation between the XPD Lys751 rs13181 polymorphism and risk of ALL. Conclusion Our research reveals that genetic variation in the genes for DNA repair may influence ALL susceptibility.

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.

RUSC1-AS1 promotes the malignant progression of breast cancer depending on the regulation of the miR-326/XRCC5 pathway.

Many long noncoding RNAs (lncRNAs) are the key regulators for cancer progression, including breast cancer (BC). RUSC1 antisense 1 (RUSC1-AS1) has been found to be highly expressed in BC, but its role and potential molecular mechanism in BC remain to be further elucidated. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was utilized to measure RUSC1-AS1, microRNA (miR)-326 and X-ray repair cross-complementing group 5 (XRCC5) expression. Cell proliferation, metastasis, cell cycle, apoptosis and angiogenesis were determined by cell counting kit-8, colony formation, transwell, flow cytometry and tube formation assays. Protein expression was detected by western blot analysis. The targeted relationship between miR-326 and RUSC1-AS1 or XRCC5 was validated using dual-luciferase reporter assay and RIP assay. Xenograft models were constructed to uncover the effect of RUSC1-AS1 on BC tumorigenesis. RUSC1-AS1 was upregulated in BC, and its downregulation suppressed BC proliferation, metastasis, cell cycle, angiogenesis, and tumor growth. MiR-326 was confirmed to be sponged by RUSC1-AS1, and its inhibitor reversed the regulation of RUSC1-AS1 silencing on BC progression. XRCC5 could be targeted by miR-326. Overexpression of XRCC5 reversed the inhibitory impacts of miR-326 on BC progression. RUSC1-AS1 could serve as a sponge of miR-326 to promote BC progression by targeting XRCC5, suggesting that RUSC1-AS1 might be a target for BC treatment.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

The Incidence of the XRCC1 rs25487 and PON1 rs662 Polymorphisms in a Population from Central Brazil: Patterns in an Area with a High Level of Agricultural Activity.

In Brazil, high levels of agricultural activity are reflected in the consumption of enormous amounts of pesticides. The production of grain in Brazil has been estimated at 289.8 million tons in the 2022 harvest, an expansion of 14.7% compared with 2021. These advances are likely associated with a progressive increase in the occupational exposure of a population to pesticides. The Paraoxonase 1 gene (PON1) is involved in liver detoxification; the rs662 variant of this gene modifies the activity of the enzyme. The repair of pesticide-induced genetic damage depends on the protein produced by the X-Ray Repair Cross-Complementing Group 1 gene (XRCC). Its function is impaired due to an rs25487 variant. The present study describes the frequencies of the rs662 and rs25487 and their haplotypes in a sample population from Goiás, Brazil. It compares the frequencies with other populations worldwide to verify the variation in the distribution of these SNPs, with 494 unrelated individuals in the state of Goiás. The A allele of the rs25487 variant had a frequency of 26% in the Goiás population, and the modified rs662 G allele had a frequency of 42.8%. Four haplotypes were recorded for the rs25487 (G > A) and rs662 (A > G) markers, with a frequency of 11.9% being recorded for the A-G haplotype (both modified alleles), 30.8% for the G-G haplotype, 14.3% for the A-A haplotype, and 42.8% for the G-A haplotype (both wild-type alleles). We demonstrated the distribution of important SNPs associated with pesticide exposure in an area with a high agricultural activity level, Central Brazil.

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.

The XRCC1 Arg194Trp polymorphism was associated with the risk of head and neck squamous cell carcinoma development: Results from a systematic review and meta-analysis.

The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05. Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR=1.182, 95%CI=1.015-1.377, p=.032; homozygous model: OR=1.274, 95%CI=0.940-1.727, p=.119; dominant model: OR=1.194, 95%CI=1.027-1.388, p=.021; recessive model: OR=1.181, 95%CI=0.885-1.576, p=.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.

Associations of rs1799794 and rs1799796 polymorphisms with risk of breast cancer: A meta-analysis.

The aim of this meta-analysis was to investigate the rs1799794 and rs1799796 polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) in relation to breast cancer susceptibility. PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies published until June 24, 2019. All analyses were carried out using Stata 14.0 software. Subgroup analyses were performed according to cancer types, ethnicity, source of controls, and method. Our meta-analysis included articles reporting 13 studies of SNP rs1799794 and seven articles reporting 10 studies of SNP rs1799796. Overall, significant associations were observed between the XRCC3 rs1799794 polymorphism and breast cancer risk in the dominant model and heterozygote model (GG + AG vs. AA: odds ratio [OR] =1.06, 95% confidence interval [CI]: 1.00-1.11, P = 0.037, I2 = 47%; AG vs. AA: OR = 1.08, 95% CI: 1.02-1.13, P = 0.006, I2 = 42.3%) and between the XRCC3 rs1799796 polymorphism and breast cancer risk in the homozygote model (GG vs. AA: OR = 0.91, 95% CI: 0.84-0.99, P = 0.021, I2 = 33.3%). The results of this meta-analysis suggest that the variant G allele of the XRCC3 rs1799794 polymorphism is a low-penetrant risk factor for developing breast cancer, whereas the variant G allele of the XRCC3 rs1799796 polymorphism has a protective effect against breast cancer development.

Ethnicity-stratified analysis of the association between XRCC3 Thr241Met polymorphism and leukemia: an updated meta-analysis

BackgroundPresently, whether X-ray repair cross complementing group 3 (XRCC3) Thr241Met polymorphism is correlated to leukemia risk remains controversial. Because of this reason, the objective of current study is to explore whether XRCC3 Thr241Met polymorphism confers risk to leukemia.MethodsTwo independent authors systematically and comprehensively searched Pubmed, Embase, the Cochrane library, Google academic, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021.ResultsOverall, significant associations between leukemia risk and XRCC3 Thr241Met polymorphism were found in Caucasian population by allele contrast (T vs. C: OR 1.20, 95% CI 1.02–1.40), homozygote comparison (TT vs. CC: OR 1.35, 95% CI 1.05–1.73), and recessive genetic model (TT vs. TC/CC: OR 1.31, 95% CI 1.04–1.64).ConclusionsThe present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population.

Impact of XRCC1 genetic variants on its tissue expression and breast cancer risk: A case-control study.

X-ray repair cross-complementing group 1 (XRCC1), a coordinator protein of the DNA repair complex, is thought to be involved in cancer progression. This case-control study aimed to investigate the association of two biallelic single-nucleotide polymorphisms (SNPs; Arg399Gln, Arg194Trp) of the XRCC1 gene with its tissue expression level and breast cancer (BC) risk in Egyptian women. This study included 100 BC female patients (case group 1) and 100 healthy females (control group 2). The XRCC1 tissue expression was assessed by immunohistochemistry (IHC). Genotyping of the two XRCC1 SNPs (Arg399Gln, Arg194Trp) using real-time polymerase chain reaction (PCR) was also conducted. The XRCC1 expression level was significantly lower in cancerous tissues than adjacent non-cancerous tissues (p < .001). The XRCC1 399Gln/Gln genotype, 399Gln allele, the dominant, and recessive models were significantly associated with lower XRCC1 expression in breast cancerous tissues and increased risk for BC (3.390-, 1.965-, 2.241-, and 2.429-folds, respectively). The XRCC1 399Gln/Gln genotype was associated with lower incidence of advanced tumor grade (OR: 0.06; 95%CI: 0.01-0.74; p=.028). Conversely, the XRCC1 Arg194Trp polymorphism did not show any significant association with either XRCC1 expression in breast cancer tissues or BC risk in all genetic models. The XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with 1.800- and 1.675-folds risk for BC, respectively. The XRCC1 gene polymorphism (Arg399Gln) is associated with reduced XRCC1 tissue expression and enhanced BC risk with a well-differentiated nature in Egyptian women. Moreover, XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with increased BC risk.

GA Genotype of the Arg280His Polymorphism on The XRCC1 Gene: Genetic Susceptibility Genotype in Differentiated Thyroid Carcinomas?

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto’s thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto’s thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p <0.001). The DTC group had the lowest frequency of AA genotype of Arg280His (35.5%, p <0.001). Among those with a family history of thyroid cancer, 78.9% had a GA genotype and 21.1% had the AA genotype of Arg280His (p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer.

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.

Excision repair cross‑complementing group 2 upregulation is a potential predictive biomarker for oral squamous cell carcinoma recurrence

Oral cancer is the fourth most common type of cancer among males in Taiwan, and the prognosis for patients with advanced-stage oral squamous cell carcinoma (OSCC) remains poor. The present study investigated the prognostic value of three DNA repair genes, namely excision repair cross-complementing group 1 (ERCC1), ERCC2 and X-ray repair cross-complementing group 1 (XRCC1) in OSCC. The protein expression levels of XRCC1, ERCC1 and ERCC2 in oral cell lines were analyzed via western blotting and immunohistochemistry using samples from 98 patients with biopsy-proven OSCC, while the χ2 test was used to analyze the clinicopathological association. Kaplan-Meier estimates were used to determine the prognostic value of XRCC1, ERCC1 and ERCC2 for overall survival, and the log-rank test was used to evaluate the significance of differences. Multivariate analysis revealed a positive association between ERCC2 expression and OSCC recurrence (19.64-fold; 95% CI, 5.00–77.1; P<0.001). In addition, the high protein expression levels of XRCC1, ERCC1 and ERCC2 were associated with poor disease-free and overall survival rates. Therefore, the present study suggested that high ERCC2 expression may be a risk factor for OSCC recurrence.

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.

Single Nucleotide Polymorphisms (SNPs) of OGG1 (Ser326Cys) and APE1 (Asp148Glu; –141T/G) Genes and Breast Cancer Risk in Filipino Women

Base excision repair (BER) pathway involves repair of damaged DNA caused by spontaneous decay of DNA, reactive oxygen species, and ionizing radiation. Polymorphisms of genes involved in the pathway have been reported to be associated with cancer risk. In this study, the association of BER gene polymorphisms with breast cancer risk in Filipino women was assessed. The polymorphisms studied included X-ray repair cross-complementing group 1 (XRCC1, Arg399Gln), 8-oxoguanine DNA glycosylase (OGG1, Ser326Cys), and apurinic/apyrimidinic endonuclease 1 (APE1, Asp148Glu; –141T/G). A total of 186 participants (93 breast cancer cases and 93 breast cancer-free control) were recruited for the study. The genotyping of samples was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). The association of polymorphisms of BER genes with breast cancer risk and gene-environment interaction was determined using the unconditional logistic regression model. Distributions of OGG1 and APE1 genotypes were in Hardy-Weinberg equilibrium (HWE); however, XRCC1 genotype distribution deviated from HWE and was not further analyzed. The analysis showed that OGG1 Ser326Cys, APE1 Asp148Glu, and APE1 –141T/G had no significant association with breast cancer risk. Also, there is no significant interaction between the three BER gene variants and family history of cancer. Lastly, no significant increased risk was observed when the combined effects of risk alleles of the three BER gene variants were determined. In conclusion, the study suggests that OGG1 Ser326Cys, APE1 Asp148Glu, and APE1 –141T/G are not good indicators of breast cancer risk in Filipino women.