Association of XRCC1 Arg399Gln and RAD51 135 G>C polymorphisms and epidemiologic risk factors with colorectal cancer among selected Filipinos

@#<p style="text-align: justify;"><strong>Objectives.</strong> Several studies have demonstrated that genetic variants of certain DNA repair genes such as the RAD51 and XRCC1 increase cancer risk substantially. The results were also observed to be race- and tumor site specific. Hence, this study aimed to determine the possible association of XRCC1 Arg399Gln and RAD51 135G>C polymorphisms combined with risk factors of colorectal cancer (CRC) among selected Filipinos.</p><p style="text-align: justify;"><strong>Methods.</strong> Genomic DNA isolated from peripheral blood samples of histologically confirmed CRC patients (n=70) and their age- and sex-matched clinically healthy controls (n=70) were analyzed for polymorphisms of XRCC1 and RAD51 genes by polymerase chain reaction.</p><p style="text-align: justify;"><strong>Results.</strong> The genotypic distribution pattern of RAD51 135G>C (p?0.05) was not significantly different between the CRC cases and controls. Significantly higher incidence (p=0.016) of the XRCC1 GG genotype was noted among the cases (n=34, 49%) compared with controls (n= 20, 29%). Individuals carrying the XRCC1 AG genotype have a lower risk of developing CRC (OR=0.42, 95% CI=0.21-0.85) than the XRCC1 GG genotype. XRCC1 AG genotype combined with alcohol drinking, smoking, or family history of cancer also showed a lower risk of developing CRC. There was no significant association between the genetic variants of RAD51 135G>C and CRC risk. Carriers of both XRCC1  GG and RAD51 CC genotypes showed a 5x higher risk (OR=5.02; 95%; CI=1.0429-24.1283) compared to those carrying other genotype combinations (p=0.028).</p><p style="text-align: justify;"><strong>Conclusions. </strong>XRCC1 Arg399Gln but not RAD51 135G>C may be associated with CRC development among Filipinos. Individuals who drink alcohol, smoke tobacco and have a family history of cancer have a lower risk of developing CRC when they are also carrying the XRCC1 AG genotype. The findings may have significant impli cations in designing personalized methods for screening, diagnosing, and treating CRC.</p>

The relationship between XRCC1 gene polymorphism and the efficacy and prognosis of TACE in patients with hepatocellular carcinoma in Nantong area / 公共卫生与预防医学

Objective To investigate the relationship between the genotypes of XRCC1 gene C26304T , G27466A, G28152A and the efficacy and prognosis of hepatocellular carcinoma in Nantong area. Methods The Genomic DNA was extracted from 252 newly diagnosed liver cancer patients admitted to the Department of Interventional Radiology, Affiliated Hospital of Nantong University from January 1, 2018 to December 31, 2018, and relevant clinical data and abdominal enhanced CT/MRI data were collected. Genotyping was performed using Panel high-throughput data analysis. All patients received TACE treatment, and abdominal enhanced CT/MRI was reexamined 4-6 weeks after treatment, and the efficacy was evaluated according to the efficacy of RECIST solid tumor. Survival of participants was followed up by telephone after 15 months. The frequency distribution differences of different genotypes in the efficacy and prognosis of different TACE treatments were compared, and the strength of association between related genotypes and the efficacy and prognosis of HCC TACE was indicated by odds ratio (OR) and its 95% confidence interval (CI). Results 1. The efficacy of TACE was better in AG patients with XRCC1 G28152A heterozygous mutation (OR=0.294, 95%CI:0.053-0.987), while there was no significant difference between patients with homozygous AA and patients with wild-type GG (OR=1.334, 95%CI:0.123-8.545). There was no significant difference in the efficacy of TACE between C26304T and G27466A genotypes. 2. Compared with the patients with wild-type GG, patients with G28152A heterozygous mutation AG were more likely to survive for 15 months and had a better prognosis after TACE (OR=0.262, 95%CI:0.051-0.988), but there was no significant difference in survival time between patients with homozygous mutation AA and patients with wild-type GG (OR=2.180, 95％CI:0.312-12.743）.There was no significant difference in survival time between the genotypes of C26304T and G27466A. Conclusion The patients with liver cancer in Nantong who carried heterozygous mutation AG at G27466A site of XRCC1 gene had better curative effect and prognosis of TACE. SNPs at C26304T and G28152A sites had no significant correlation with curative effect and prognosis of TACE.

Effect of Arg399Gln single-nucleotide polymorphism in XRCC1 gene on survival rate of Indian squamous cell head-and-neck cancer patients

Background: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%–40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. Materials and Methods: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. Results: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33–39.5), 38.6 (95% CI: 35.3–41.9), 35.8 (95% CI: 28.6–42.9), and 26.4 (95% CI: 13.7–39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4–39.1), 38.2 (95% CI: 34.3–42.1), 32.7 (95% CI: 26.2–39.1), and 22.3 (95% CI: 9.4–35.3) (P = 0.061), respectively. Conclusions: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment

Análise da imunoexpressão de proteínas de reparo do DNA envolvidas nas vias BER e NER em lesões odontogênicas epiteliais benignas / Immunoexpression analysis of DNA repair proteins involved in BER and NER pathways in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas apresentam comportamento biológico heterogêneo e patogênese ainda não totalmente esclarecida. As vias de reparo do ácido desoxirribonucleico (DNA) atuam em tipos específicos de danos ao material genético, realizando o reparo e regulando diversos processos celulares. Dentre as principais vias de reparo do DNA, destacamse o reparo por excisão de bases (BER) e o reparo por excisão de nucleotídeos (NER). Investigações têm demonstrado que as proteínas envolvidas nessas vias se encontram desreguladas e, por vezes, altamente expressas em algumas neoplasias malignas, contribuindo para a progressão tumoral. Levando em consideração a heterogeneidade do comportamento biológico das lesões odontogênicas epiteliais benignas e a escassez de estudos que tenham avaliado a expressão de proteínas de reparo do DNA nestas lesões, este trabalho avaliou a imunoexpressão de proteínas da via BER (APE-1 e XRCC-1) e NER (XPF) em ameloblastomas (AMEs) sólidos (n = 30), ceratocistos odontogênicos não sindrômicos (CONS) (n = 30), ceratocistos odontogênicos sindrômicos (COS) (associados à Síndrome de Gorlin) (n = 29), cistos dentígeros (CDs) (n = 30) e folículos dentários (FDs) (n = 20). A análise da expressão imunoistoquímica de APE-1, XRCC-1 e XPF foi realizada de forma quantitativa por um avaliador previamente calibrado e sem acesso aos dados clínicos dos casos. Em cinco campos de maior imunorreatividade, foram quantificadas as células positivas e negativas para as proteínas no componente epitelial de todos os casos, sendo estabelecido o percentual de células positivas em relação ao número total de células contadas para cada anticorpo. As marcações nucleares e citoplasmáticas foram analisadas separadamente para APE-1 e XPF, enquanto apenas a imunoexpressão nuclear foi considerada para XRCC-1. As comparações das medianas dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de APE-1, XRCC-1 e XPF foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foi verificada uma maior imunoexpressão nuclear de APE-1 nos CONSs, COSs e AMEs sólidos, em comparação com os CDs (p < 0,001). Dentre todos os grupos avaliados, a expressão citoplasmática de APE1 só foi encontrada em 4 CONSs e 6 COSs. A expressão nuclear de XRCC-1 foi estatisticamente maior nos CONSs e COSs em relação aos CDs (p < 0,05). Em nível nuclear, a expressão de XPF foi significativamente maior nos CONSs e COSs em relação aos CDs e AMEs (p < 0,05) e, embora sem significância estatística, foi observada uma maior expressão nuclear dessa proteína nos AMEs quando comparado aos CDs. Em relação à expressão citoplasmática de XPF, foi observada uma maior expressão nos COSs em relação aos CDs (p = 0,04). Nenhuma diferença estatisticamente significativa foi encontrada entre as expressões nucleares de APE-1, XRCC-1 e XPF entre CONSs e COSs (p > 0,05). Além disso, todas as lesões odontogênicas estudadas revelaram uma maior expressão estatisticamente significativa de APE-1 (nuclear), XRCC-1 (nuclear) e XPF (nuclear e citoplasmática) quando comparados aos FDs (p < 0,05). Para todas as lesões, o teste de correlação de Spearman mostrou uma correlação positiva entre a expressão nuclear de APE-1 e XRCC-1 ou XPF, em nível nuclear (p < 0,05). Os resultados deste estudo sugerem um potencial envolvimento das proteínas APE-1, XRCC-1 e XPF na patogênese das lesões odontogênicas epiteliais benignas, com destaque para aquelas com comportamento biológico mais agressivo (AU).

The benign epithelial odontogenic lesions present a heterogeneous biological behavior and their pathogenesis are not fully understood. The deoxyribonucleic acid (DNA) repair pathways act on specific types of damage to the genetic material, performing the repair and regulating several cellular processes. Among the main DNA repair pathways, the most notable are the base excision repair (BER) and the nucleotide excision repair (NER). Investigations have shown that the proteins involved in these pathways are deregulated and sometimes highly expressed in some malignancies, contributing to tumor progression. Taking into account the heterogeneity of the biological behavior of benign epithelial odontogenic lesions and the scarcity of studies that have evaluated the expression of DNA repair proteins in these lesions, this study evaluated the immunoexpression of BER (APE-1 and XRCC-1) proteins and NER (XPF) in solid ameloblastomas (AMEs) (n = 30), non-syndromic odontogenic keratocysts (NSOKCs) (n = 30), syndromic odontogenic keratocysts (SKOCs) (associated with Gorlin's Syndrome) (n = 29), dentigerous cysts (DCs) (n = 30) and dental follicles (DFs) (n = 20). The immunohistochemical analysis of APE-1, XRCC-1 and XPF was performed quantitatively by a previously calibrated evaluator and without access to the clinical data of the cases. In five fields of higher immunoreactivity, positive and negative cells were quantified for the proteins in the epithelial component of all cases, and the percentage of positive cells was established in relation to the total number of cells counted for each antibody. Nuclear and cytoplasmic markers were analyzed separately for APE-1 and XPF, while only nuclear immunoexpression was considered for XRCC-1. The comparisons of the median percentages of immunoreactivity in relation to the studied groups were performed using the non-parametric Kruskal-Wallis and MannWhitney tests. Possible correlations between the expression of APE-1, XRCC-1 and XPF were assessed by Spearman's correlation test. The level of significance was set at 5% (p < 0.05). A higher nuclear immunoexpression of APE-1 in the NSOKCs, SOKCs and solid AMEs was verified in comparison with the DCs (p < 0.001). Among all the evaluated groups, the cytoplasmic expression of APE-1 was only found in 4 NSOKCs and 6 SOKCs. Nuclear expression of XRCC-1 was statistically higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was significantly higher in NSOKCs and SOKCs than in DCs and AMEs (p < 0.05) and, although without statistical significance, a higher nuclear expression of this protein was observed in AMEs when compared to CDs. Regarding the cytoplasmic expression of XPF, a greater expression was observed in the SOKCs in relation to the DCs (p = 0.04). No statistically significant difference was found between the nuclear expressions of APE-1, XRCC-1 and XPF between NSOKCs and SOKCs (p > 0.05). In addition, all the odontogenic lesions studied revealed a statistically significant expression of APE-1 (nuclear), XRCC-1 (nuclear) and XPF (nuclear and cytoplasmic) when compared to DFs (p < 0.05). For all lesions, Spearman's correlation test showed a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF at the nuclear level (p < 0.05). The results of this study suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions. The role played by these proteins may be more important in odontogenic lesions with more aggressive biological behavior (AU).

The Role of TNF-Alpha, Beta, XRCC1 and p53 Gene Predisposition in Cancers

Cancer is a group of diseases characterized by abnormal and uncontrolled cellular growth and differentiation. The major cause of Cancer consists of different types of genetic alterations that include gene substitutions, point mutations and gene amplification leading to damage in molecular pathways responsible for cell growth, survival, and metastasis. These changes develop in the majority of cases with a specific type of tumor. Genes can be used as biomarkers for identification and development of targeted treatments and also for predicting various responses to therapies. The aim of the present review is to reveal the role of tumorigenesis in TNF alpha, beta, xrcc1 and p53 genes in cancer susceptibility to gene predisposition.

Association of XRCC1,P53 and COX-2 genetic polymorphisms with susceptibility of esophageal cancer in Hakka population / 实用医学杂志

Objective To explore the role of genetic factors in development of esophageal cancer by studying the association of XRCC1,P53 and COX-2 genetic polymorphisms with susceptibility of esophageal cancer in Hakka population. Methods A case-control study was performed with molecular epidemiological methods. A total of 122 patients with esophageal cancer(esophageal cancer group)and 123 healthy people(control group) were randomly selected from Hakka people in Meizhou area. The genotypes and alleles of XRCC1 rs25487,P53 rs1042522,and COX-2 rs689466 in both groups were detected,and the distribution characteristics were analyzed. Results The polymorphisms of XRCC1 rs25487(A/G),P53 rs1042522(C/G)and COX-2 rs689466(A/G)were found in Hakkan people in Meizhou area ,but there were no significant differences in the genotype and allele fre-quencies between the two groups. And after such as sex,age,stratified analysis showed also no significant results. Conclusions The study shows that the genetic polymorphisms of XRCC1 gene rs25487,P53 gene rs1042522 and COX-2 gene rs689466 are possibly not related with the susceptibility of esophageal cancer in Hakka population in Meizhou area.

Correlation Analysis of XRCC1 rs25487 Polymorphism with the Occurrence of Lung Cancer / 中国药房

OBJECTIVE:To investigate the correlation of XRCC1 rs25487 polymorphism with the occurrence of lung cancer. METHODS:A total of 208 patients with primary lung cancer of Han nationality in Northern Jiangsu selected from the Affiliated Hospital of Xuzhou Medical University during Sept. 2015-Jul. 2016 were included in lung cancer group. A total of 214 healthy volunteers of the hospital underwent physical examination were included in control group. PCR-RFLP was used to detect the genotypes at XRCC1 rs25487 locus,and Logistic regression model was used to evaluate the correlation of genotypes with the occurrence of lung cancer. RESULTS:There was no statistical significance in the distribution of age and gender between 2 groups (P＞0.05). The proportion of smoker in lung cancer group was significantly higher than control group,with statistical significance(P＜0.05). AA,AG and GG genotypes were detected at rs25487 locus of XRCC1 gene. The frequency of AA,AG and GG genotype were 43.5%,41.1%and 15.4% in control group and 28.8%,48.6% and 22.6% in lung cancer group,respectively. The frequencies of genotypes in 2 groups were in line with Hardy-Weinberg equilibrium(P＞0.05),but there was statistical significance in genotype distribution between 2 groups(P＜0.05). Compared with AA genotype,the risk of lung cancer in individuals carrying AG genotype increased by 2.265 fold [OR＝2.265,95%CI(1.299,3.950),P＝0.040;after corrected with gender,age and smoking history OR＝2.309,95%CI(1.274, 4.185),P＝0.006],with statistical significance. The risk of lung cancer in individuals carrying GG genotype increased by 1.310 fold [OR＝1.310,95%CI(0.771,2.228),P＝0.318;after corrected OR＝1.429,95%CI(0.811,2.518),P＝0.217],without statistical significance. CONCLUSIONS:rs25487 locus mutant heterozy-gosity of XRCC1 gene is risk factor of lung cancer in Han nationality from Northern Jiangsu,and smoking can increase the risk of lung cancer.

Associations of XRCC1 S326C (rs25487) gene Polymorphism in Myelodysplastic syndrome / Эрүүл мэндийн лаборатори

Introduction@#Base excision repair (BER) is mainly responsible for the correction of small base changes of DNA damage. BER pathway involved many enzymes including OGG1 and XRCC1. The defective DNA repair is associated with an increased risk of various cancers including hematologic malignancies-leukemia and myelodysplastic syndrome (MDS). However, it is deniably these polymorphisms alter the susceptibility and clinical outcome of MDS patients.@*The aim@#This study was to evaluate the impact of polymorphisms in gene encoding one protein of BER system: XRCC1 Arg399Gln in MDS and healthy population.@*Methods@#In this study, we recruited 60 health control group [median 47.9 years, 9 MDS subjects [median 56.6 years] were included in this study. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Allele and genotype frequencies were calculated by direct counting.@*Result@#The frequencies of genotypes of XRCC1 Arg399Gln were as follows: Arg /Arg 1 (11%), Arg/Gln 6 (66%), Gln/Gln 2 (22%) in MDS and Arg /Arg 18.4%, Arg/Gln40%, Gln/Gln41.6% in health control for XRCC1 Arg399Gln. The result revealed that genotypes Arg399Gln increased the risk of MDS@*In conclusion@#this study is the first to analyze XRCC1 SNPs and their associated risk of MDS in Mongolian samples. To fully understand the role of DNA damage and DNA repair in the MDS, prospective studies are needed and other genes (OGG1 Ser326Cys, MUTYH Gln324His, APE Asp148Glu) of base excision repair pathway should be analyzed.

Study on XRCC1 gene polymorphisms and EBV infection in nasopharyngeal carcinoma and underlying mechanism / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the relationship between genetic polymorphim of X-ray repair cross complementing gene 1(XRCC1) and EBV infection in NPC cell.METHODS NPC CNE cell strain was divided into different groups depending on its XRCC1 genetic polymorphism,and EBV was transferred into different groups.Characteristics of cells and XRCC1 protein were detected among different groups before and after EBV transferring.RESULTS There was no difference in cell characteristics and XRCC1 protein level among different genotypes in NPC CNE cells strain.After EBV transferring,there was an increasing in cell malignancy in NPC cells,including control group,wild type group,and 194,280,399 mutant genotype groups,and the differences were statistically significant(P>0.05).There was no difference in XRCC1 protein level before and after EBV transferring.Compared with other groups,the increasing in cell malignancy was less in the 194 mutant genotype group before and after EBV transferring,especially in cell migration and proliferation.There were no difference in the increasing of cell malignancy and XRCC1 protein level among control group,wild type and 280,399 mutant genotypes of NPC CNE cells before and after EBV transferring.CONCLUSION The results suggest that EBV transferring can raise the carcinogenicity of NPC cell.After EBV transferring,the 194 mutant genotype is associated with a reduced carcinogenicity of NPC cells compared with other genotypes.

Effects of XRCC1 Polymorphism on Efficacy of Chemotherapy and Survival Time of Advanced Gastric Cancer Patients / 中国药房

OBJECTIVE:To investigate the effect of X-ray repair cross complementing gene(XRCC1)Arg399Gln(G→A) polymorphism on efficacy of oxaliplatin+fluorouracil chemotherapy and survival time of advanced gastric cancer patients. METH-ODS:Totally 52 cases of advanced gastric cancer were selected from Hainan Provincial People's Hospital during Jan. 2013-Jan. 2015. They were given oxaliplatin+fluorouracil chemotherapy,for 3 courses(a treatment course lasted for 3 weeks). The genotypes of patients were detected by PCR-LDR. Disease control rate and progression free survival were compared among different geno-types. RESULTS:Among 52 cases of advanced gastric cancer,there were 28 cases of XRCC1 GG genotype(53.8%),21 cases of GA genotype(40.4%),3 cases of AA genotype(5.8%),frequencies of which were all in line with Hardy-Weinberg balance(P>0.05). Disease control rates of 52 cases were 76.9%,among which disease control rate(92.9%)of GG genotype was significantly higher than that of GA+AA genotype(58.3%),with statistical significance(P<0.05). The average progression free survival of 52 cases was(7.1+1.2)months,among which progression free survival of GG genotype [(8.6±0.8)months] was significantly longer than that of GG+GA genotype [(5.9 ± 0.7)months],with statistical significance (P<0.05). CONCLUSIONS:XRCC1 polymor-phism is correlated with efficacy of oxaliplatin+fluorouracil chemotherapy and progression free survival,and XRCC1 GG genotype is more sensitive to chemotherapy drugs. XRCC1 gene can be regarded as predictive indicator for therapeutic efficacy of chemothera-py and survival.

Associação da imunoexpressão das proteínas XRCC1, TFIIH E XPF com características clinicopatológicas e sobrevida em carcinoma epidermoide de língua oral / Association of immunoexpression of XRCC1, TFIIH and XPF proteins with clinicopathological characteristics and survival in oral tongue squamous cell carcinoma

Sistemas de reparo do DNA, genes e proteínas, são essenciais para manutenção da integridade do genoma, evitando graves doenças como o câncer. Desrregulação na expressão destas proteínas vem sendo associado tanto ao risco do desenvolvimento, como na evolução de variados cânceres humanos com destaque para o carcinoma epidermoide oral. O objetivo deste trabalho foi analisar a imunoexpressão das proteínas de reparo do DNA, XRCC1, THIIF e XPF em carcinoma epidermoide de língua oral (CELO) e investigar associação com parâmetros clínicos, histopatológicos, de desfecho e sobrevida em cinco anos. Setenta e quatro casos de CELO foram analisados por meio da técnica da imuno-histoquímica de forma semiquantitativa. Observou-se alta expressão das proteínas pesquisadas nas células parenquimatosas, identificando associação significativa da elevada expressão de XRCC1 com melhor estadiamento clínico (p=0,02). A regressão de Cox revelou tamanho do tumor (p<0,01), comprometimento linfonodal (p=0,04), estágio do tumor (p=0,02) e profundidade de invasão >4mm (p=0,05) como fatores prognósticos para CELO. Os resultados deste experimento sugerem que as proteínas XRCC1, TFIIH e XPF participam do processo de tumorigênese, entretanto a imunoexpressão das mesmas não pode ser utilizada como indicador independente de prognóstico para CELO (AU).

DNA repair systems, genes and proteins are essential for genome integrity maintenance, avoiding serious diseases such as cancer. Deregulation in the expression of those proteins has been associated with both the risk of development and evolution of various human cancers, including oral squamous cell carcinoma. The purpose of this study was to analyze the immunoreactivity of the DNA repair proteins XRCC1, THIIF and XPF in oral tongue squamous cell carcinoma (OTSCC) and to investigate its association with clinical and histopathological parameters, outcome and 5-year survival rate. Seventy-four cases of OTSCC were analyzed semi-quantitatively through immunohistochemistry. We observed that DNA repair proteins were highly expressed in parenchymal cells; however, we only observed a significant association between XRCC1 high expression and better clinical staging (p=0,02). Cox regression showed that tumor size (p<0,01), lymph node involvement (p=0,04), tumor stage (p=0,02) and depth of invasion> 4mm (p=0,05) were prognostic factors. The results of this experiment suggest that XRCC1, TFIIH and XPF participate in the tumorigenic process, however, their immunoexpression may not be used as an independent prognostic indicator for OTSCC (AU).

XRCC1 rs25487 locus genetic polymorphisms and susceptibility to nonobstructive azoospermia in Hui minority ethnic population of Shaanxi province / 西安交通大学学报(医学版)

Objective To explore the association between X-ray repair cross complementing group 1 (XRCC1)gene rs25487 locus polymorphisms and nonobstructive azoospermia in Hui minority ethic population of Shaanxi Province.Methods We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)method for genotyping at XRCC1 gene rs25487 locus in 79 patients with nonobstructive azoospermia and 82 healthy male controls in Hui minority ethic population of Shaanxi Province.Then we analyzed the association be-tween XRCC1 gene rs25487 locus and nonobstructive azoospermia.Results Compared with GG genotype,GA, AA and GA + AA genotypes demonstrated a significantly increased risk for nonobstructive azoospermia (OR =2.286,95% CI 1.1 5 1-4.539;OR =2.202,95% CI 0.753-6.439;OR =2.271,95% CI 1.1 71-4.403),respec-tively.Meanwhile,the A allele frequency was significantly higher in azoospermic patients than in controls (OR =1.582,95% CI 1.005-2.492,P =0.047).Conclusion G→A in XRCC1 gene rs25487 locus is correlated with nonobstructive azoospermia in Hui minority ethic population of Shaanxi province.

Relationship between FOLFOX Chemotherapy of Colorectal Cancer Patients and GSTP1,XRCC1 Gene Polymorphism / 现代检验医学杂志

Objective To explore the relationship between FOLFOX Chemotherapy and GSTP1,XRCC1 gene polymorphism in patients with colorectal cancer.Methods 60 cases of colorectal cancer treated in Tumor hospital of Hunan Province from January to December 2014 were selected as the research object.Treat patients with modified FOLFOX regimen,determined the GSTP1 ,XRCC1 gene sequence polymorphism,and explored the relationship between the efficacy and the GSTP1 ,XRCC1 gene sequence polymorphism.Results The number of patients with complete remission and partial remission and the num-ber of patients with stable and progress were not related to the gender,age,tumor location,pathological differentiation,TNM staging of patients (χ2=0.222~1.8,P>0.05).Of all cases,the frequencies of GSTP1A/A,A/G and G/G genotype were 68.3%,23.3% and 8.3%,respectively.GSTP1 gene wild-type (A/A)patients were treated with less efficiency than the GSTP1 gene mutation type (A/G+G/G)patients (χ2=4.493,P=0.034).Of all cases,the frequencies of XRCC1 G/G,G/A and A/A genotype were 58.3%,36.7% and 5%,respectively.XRCC1 gene wild type (G/G)patients with effective rate was higher than that of mutant type (G/A+A/A)patients (χ2=4.691,P=0.030).Conclusion The study showed that GSTP1(A/A),XRCC1 (G/G)gene polymorphism may be associated with clinical response to FOLFOX chemotherapy in advanced colorectal cancer.

Identification of polymorphisms of XRCC1 gene in patients with cancer in a city of northern Brazil / Identificação dos polimorfismos do gene XRCC1 em indivíduos com câncer em uma cidade da Região Norte do Brasil

ABSTRACT Introduction: Cancer is considered a genetic disease. For this reason, identification and characterization of the genes involved in its origin and progression are of fundamental importance in understanding its molecular basis. Objective: Our objective was to determine whether people from Macapá with a diagnosis of cancer have genetic polymorphisms related to the XRCC1 gene. Materials and methods: We analyzed 30 samples of deoxyribonucleic acid (DNA) of cases with cancer and 30 control samples. All samples were amplified and analyzed by the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method, with the use of restriction enzyme MspI. Results: Regarding the 194T polymorphism, we found that all samples of the cases presented the polymorphic allele Trp (Arg/Trp). In control samples, 96.6% also identify the polymorphic allele Trp and, among these, one was homozygous for the same allele (Trp/Trp). Regarding the 399A polymorphism, 83.3% of the cases and 23.3% of the controls had the Arg/ Gln genotype, respectively. We found that 73.3% of controls and 16.6% of cases had the Arg/Arg genotype. Among the controls, we found only a sample that was homozygous for the polymorphic allele Trp/Trp. Conclusion: Our results demonstrated the allele frequency of 194Trp polymorphism in both sample groups analyzed. We also found a significant number of polymorphic allele 399A in people with cancer. Thus, we can highlight 399Gln polymorphism as a genetic marker of cancer risk in this population. .

RESUMO Introdução: O câncer é considerado uma doença genética, por isso identificar e caracterizar os genes envolvidos em sua origem e progressão é fundamental para compreender suas bases moleculares. Objetivos: Nosso objetivo foi verificar se os indivíduos de Macapá com diagnóstico de câncer apresentavam os polimorfismos genéticos relacionados com o gene XRCC1. Materiais e métodos: Foram analisadas 30 amostras de ácido desoxirribonucleico (DNA) de indivíduos com câncer e 30 amostras controle. Todas elas foram amplificadas e analisadas pela técnica de reação em cadeia da polimerase (PCR)-polimorfismo de tamanho de fragmentos de restrição (RFLP), com a utilização da enzima de restrição MspI. Resultados: Com relação ao polimorfismo 194T, observamos que todas as amostras dos casos apresentaram o alelo polimórfico Trp (Arg/Trp). Nas amostras controle, em 96,6% também identificamos o alelo polimórfico Trp e, entre essas, uma foi homozigota para o mesmo alelo (Trp/Trp). Quanto ao polimorfismo 399A, 83,3% das amostras dos indivíduos com câncer e 23,3% das amostras controle apresentaram o genótipo Arg/Gln. Verificamos que 73,3% dos controles e 16,6% dos casos apresentaram genótipo Arg/Arg. Encontramos apenas uma amostra, entre os controles, homozigota para o alelo polimórfico Trp/Trp. Conclusão: Nossos resultados demonstraram a frequência do alelo polimórfico 194Trp nos dois grupos amostrais analisados. Encontramos também um número significativo do alelo polimórfico 399A em indivíduos com câncer. Desse modo, podemos destacar o polimorfismo 399Gln como possível marcador genético para ser usado no prognóstico do câncer nessa população. .

Avaliação de polimorfismos funcionais nos genes de reparo XRCC1, APEX1, XPD e XPF em carcinomas de células escamosas orais / Evaluation of functional polymorphisms in the repair genes XRCC1, APEX1, XPD and XPF in oral squamous cell carcinomas

As vias de reparo por excisão de base (BER) e por excisão de nucleotídeo (NER) desempenham um papel crucial na manutenção da integridade genômica. Polimorfismos em genes das vias BER e NER, que modulam a capacidade de reparo do DNA, podem estar relacionados ao risco de desenvolvimento e prognóstico do câncer oral. O presente trabalho teve como objetivo investigar a frequência de polimorfismos de nucleotídeos simples, em dois genes da via de reparo do DNA por excisão de base (XRCC1 ­ rs25487 e APEX1 ­ rs1130409) e dois genes da via de reparo por excisão de nucleotídeo (XPD ­ rs13181 e XPF ­ rs1799797), em pacientes com carcinoma de células escamosas oral (CCEO), buscando associações com o risco de desenvolver esta neoplasia maligna e o seu prognóstico. Um total de 92 amostras de DNA de pacientes com CCEO e 130 controles foram genotipadas utilizando o método da reação em cadeia da polimerase em tempo real. O software estatístico GraphPad Prism version 6.0.1. foi utilizado para a aplicação dos testes apropriados. Odds ratio (OR) e hazard ratio (HR), e seus intervalos de confiança (IC) de 95%, foram calculados pela regressão logística. A avaliação do prognóstico foi realizada por meio da curva de Kaplan-Meier e análise multivariada de Cox. A presença das variantes polimórficas nos genes XRCC1, APEX1, XPD, e XPF não foram associadas ao risco de desenvolver CCEO. A interação da presença da variante polimórfica com o hábito de fumar não foi significativa para nenhum dos polimorfismos analisados. Já a presença do polimorfismo em XPD, somada ao hábito de beber, aumentou o risco de desenvolver CCEO (OR 1,86, 95% IC: 0,86 ­ 4,01, p=0,03). Apenas o SNP do APEX1 (rs1130409) esteve associado a uma diminuição da sobrevida específica (HR 3,94, 95% IC: 1,31 ­ 11,88, p=0,01). O presente estudo sugere uma interação entre o consumo de álcool e a presença do polimorfismo estudado no gene XPD. Além disso, indica um pior prognóstico para pacientes que possuem o polimorfismo estudado em APEX1 (AU).

Base excision repair (BER) and nucleotide excision repair (NER) pathways play critical role in maintaining genome integrity. Polymorphisms in BER and NER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of oral cancer. This study was conducted with genomic DNA from 92 patients with oral squamous cell carcinomas (OSCC) and 130 controls. The cases were followed up to explore the associations between BER and NER genes polymorphisms and the risk and prognosis of OSCC. Four single-nucleotide polymorphisms (SNPs) in XRCC1 (rs25487), APEX1 (rs1130409), XPD (rs13181) and XPF (rs1799797) genes were tested by polymerase chain reaction ­ quantitative real time method. The GraphPad Prism version 6.0.1 statistical software was applied for statistical analysis of association. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by logistic regression. Kaplan-Meier curve and Cox proportional hazard model were used for prognostic analysis. The presence of polymorphic variants in XRCC1, APEX1, XPD and XPF genes were not associated with an increased risk of OSCC. Gene-environment interactions with smoking were not significant for any polymorphism. The presence of polymorphic variants of the XPD gene in association with alcohol consumption conferred an increased risk of 1.86 (95% CI: 0.86 ­ 4.01, p=0.03) for OSCC. Only APEX1 was associated with decreased specific survival (HR 3.94, 95% CI: 1.31 ­ 11.88, p=0.01). These results suggest an interaction between polymorphic variants of the XPF gene and alcohol consumption. Additionally APEX1 may represent a prognostic marker for OSCC (AU).

Association between Polymorphisms of XRCC1 and TP53 Genes and Endometriosis.

Endometriosis is a complex disorder of the female reproductive system where endometrial tissue embeds and grows at extrauterine location. Polymorphisms in several genes have been studied as probable risk factors of this debilitating disease. Aims: To investigate the association between polymorphisms in DNA repair pathway genes, namely XRCC1 Arg399Gln and TP53 codon 72 and risk of developing endometriosis. Study Design: The study was conducted at Medical Biochemistry Department, Menoufia University and Obstetrics and Gynecology Department, Mansoura University between May 2012 and June 2014. Methodology: Genotyping of XRCC1 Arg399Gln by PCR-CTPP and TP53 codon 72 using allelespecific PCR techniques were conducted on 85 endometriosis patients and 60 healthy controls. Results: This study found that TP53 Pro/Pro and XRCC1 399 Gln/Gln homozygotes had a 5.11 and 4.19 fold increased risk to develop endometriosis when compared to the arginine homozygotes, respectively. This association between TP53 codon 72 Pro/Pro genotype and the risk of endometriosis was also clearly evident in endometriosis patients with stage III and IV (4.6 fold increased risk to develop endometriosis). However, the association between XRCC1 399 Gln/Gln genotype and endometriosis stage was not statistically significant (P=0.16). Anon significant higher risk of endometriosis was associated with the presence of two risk genotypes, with OR values of 1.6 (95% CI = 0.64-3.8). Conclusion: It could be concluded that XRCC1 399Gln and TP53 72Pro alleles are significantly associated with an increased risk for endometriosis. More than one gene variant didn't significantly increase the risk of endometriosis. Therefore, further larger population-based studies including other DNA repair pathway genes are needed in order to confirm the possible relationship between DNA repair gene polymorphisms and endometriosis risk.

Polymorphism of XRCC1 gene and its relation with genetic susceptibility of nasopharyngeal carcinoma in chinese living in jiangsu, zhejiang province and shanghai / 第二军医大学学报

Objective To study the polymorphism of XRCC1 gene and its relation with genetic susceptibility of the nasopharyngeal carcinoma (NPC) in Chinese living in Jiangsu, Zhejiang Province and Shanghai. Methods A case-control study was performed with 87 NPC patients and 94 healthy controls ofHan nationality in Chinese living in Jiangsu, Zhejiang Province and Shanghai. The two groups were matched by sex and age. PCR-RFLP technique was used to explore the relation of different XRCC1 polymorphismswith the susceptibility of NPC. Results The frequencies of the genotypes of XRCC1 Argl94Trp and Arg399Gln were similar between NPC andcontrol groups. The risk of NPC individuals with the Trp194Trp genotype was reduced compared with that in those with Argl94Arg genotype, but with no significant differences (0R = 0. 41, 95% CI:0. 081. 65, P = 0. 21). No association was observed between the genetic susceptibility ofNPC and other Argl94Trp variants or all Arg399Gln variants. Conclusion Our findings suggest that the polymorphism of XRCC1 has no association with the risk of nasopharyngeal carcinoma inChinese living in Jiangsu, Zhejiang Province and Shanghai, but the Trp194Trp variant genotype may be associated with a reduced risk of NPC.

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.

DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia

DNA repair is one of the central defense mechanisms against mutagenic exposures. Inherited SNPs of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. Saudi Arabia harbors enormous genetic and cultural diversity. In the present study we aimed to determine the genotype and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386 healthy individuals residing in the central region of Saudi Arabia and compare them with HapMap and other populations. The genotype and allele frequencies of the four DNA repair gene loci in central Saudi population showed a distinctive pattern. Furthermore, comparison of polymorphisms in these genes with other populations also showed a unique pattern for the central Saudi population. To the best of our knowledge, this is the first report that deals with these DNA repair gene polymorphisms among the central Saudi population.

Association between XPC and XRCC1 polymorphism and prognosis of primary hepatocellular carcinoma after radical resection / 中国癌症杂志

10.3969/j.issn.1007-3969.2013.04.005