ERCC1 polymorphism and its expression associated with ischemic stroke in Chinese population
Xiao‐Dong DengKe JianlinTaiyu ChenQin GaoZhuolin ZhaoWei ZhangHuan LiuMingliang XiangLizhen WangYing MaYun Liu
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Background Excision repair cross-complementing group 1 ( ERCC1 ) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke. Methods A total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR ( qPCR ) and enzyme-linked immunosorbent assay ( ELISA ), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism ( RFLP-PCR ) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed. Results The ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group ( P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group ( P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076–1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744–3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028–1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087–3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype ( P < 0.05). Conclusion It was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.Keywords:
ERCC1
Stroke
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Proteins of the nucleotide excision repair pathway can repair DNA damage. The excision repair cross-complementing (ERCC) gene family reduce damagement of DNA by nucleotide excision and repair. The aim of this study is to investigate the expressions of ERCC1 (members of DNA repair gene family) in patients with non-small cell lung cancer (NSCLC) as well as their clinical prognostic significance.Expression levels ofERCC1 were detected by IHC in 118 stage I NSCLC patients. Kaplan-Meier survival curve, and Cox multivariate regression analysis were used for statistical analysis.The patients with high expression of ERCC1 had significantly longer survival time than those with low expression of ERCC1, and Cox multivariate regression analysis showed that expression of RRM1 was an independent prognostic factor for NSCLC patients.NSCLC patients with high ERCC1 expression have a better survival when compared to patients with low ERCC1 expression. Therefore, an intact DNA repair mechanism may reduce the accumulation of genetic aberrations that are thought to contribute to a tumor malignant potential and therefore the risk of relapse after definitive treatment.
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ERCC1 is a key regulator of nucleotide excision repair (NER) pathway that repairs bulky DNA adducts, including intrastrand DNA adducts and interstrand crosslinks (ICLs). Overexpression of ERCC1 has been linked to increased DNA repair capacity and platinum resistance in solid tumors. Multiple single nucleotide polymorphisms (SNPs) have been detected in ERCC1 gene that may affect ERCC1 protein expression. Platinum-based treatment remains the cornerstone of urothelial cancer treatment. Given the expanding application of neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer, there is an emerging need for biomarkers that could distinguish potential responders to cisplatin treatment. Extensive research has been done regarding the prognostic and predictive role of ERCC1 gene expression and polymorphisms in bladder cancer. Moreover, novel compounds have been recently developed to target ERCC1 protein function in order to maximize sensitivity to cisplatin. We aim to review all the existing literature regarding the role of the ERCC1 gene in bladder cancer and address future perspectives for its clinical application.
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Cisplatin is one of the major drugs that used in the treatment of oral cancer.Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. The aim of this study was to investigate the association between polymorphisms in ERCC1 (C118T & C8092A) genes and the response to cisplatin-based chemotherapy.ERCC1polymorphisms (C118T & C8092A) were studied using PCR-RFLP method from 150 OSCC patients as cases as well as 150 normal tissues from the same patients were collected as controls for this study. Results: Frequencies of ERCC1 C118C, C118T and T118T genotypes were 60%, 28% and 12% in OSCC patients and 78%, 19% and 3% in the controls, respectively. The C118T & T118T genotype had a 1.69 and 4.97 -folds increased risk for OSCC. Frequencies of ERCC1 C8092C, C8092A and A8092A were 78%, 18% and 4% in the OSCC patients and 89%, 10%, amd 1% in the controls, respectively. The C8092A genotype showed a 1.97-fold increased risk for OSCC.In conclusion, this study highlights the DNA repair gene polymorphisms that might play a role in mediating susceptibility to oral squamous cell carcinoma and cisplatin therapy. Our data suggest that the ERCC1 C118T, T118T and ERCC1 C8092A genotypes are genetic risk factors for Oral squamous cell carcinoma and ERCC1 118 C/T and C8092A polymorphisms have significant influence on clinical outcome.
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Objective To investigate the correlation between excision repair cross-complementing 1 ( ERCC1) expression and cisplatin sensitivity in non-small cell lung cancer ( NSCLC). Methods A total of 168 NSCLC patients were selected from our hospital from January 2005 to December 2007. The expression of ERCC1 protein was analyzed by immuohistochemistry and ERCC1 mRNA tested by RT-PCR. Analyses were performed to determine the correlation between expression of ERCC1 and chemotherapeutic sensitivity in NSCLC. Results A positive expression of F.RCC1 protein was found in 99 ( 58. 93% ) patients. The expression of ERCC1 had no correlation with gender, age, stage and pathological types ( P >0. 05). Among all patients, 133 were followed up for about 3-5 years and 91 cases belonged to the responding group. Three cases with stage I a-I b underwent only operation without chemotherapy. And 76 (58. 46% ) patients were positive for ERCC1 expression in 130 cases. In the responding group, 38 (43. 18% ) cases had a positive expression of ERCC1 and 50 (56. 82% ) cases a negative expression of ERCC1. In the non-responding group, 37 (88. 10%) cases had a positive expression of ERCC1 and 5 ( 11.90%) cases a negative expression of ERCC1. The expression of ERCC1 decreased in the responding group versus the nonresponding group (x2 =23. 50, P <0. 01). The expressions of ERCC1 mRNA were (0. 624±0.275)and (2.758±0.771) in the responding and non-responding groups respectively (t = 11.54, P =0.013).Conclusion An elevated expression of ERCC1 is an important factor for cisplatin insensitivity in NSCLC. Itmay provide an useful reference for designing individualized chemotherapeutic regimens for NSCLC patients.repair cross-complementing 1; Cisplatin
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Non-small cell lung cancer; Excision
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The response of tumor cells to platinum-based chemotherapy involves DNA repair mechanisms. Excision repair cross-complementation group 1 (ercc1) is one of the leading genes involved in DNA repair, and several studies have linked ercc1 to platinum resistance in cell lines and in human cancers. A common single nucleotide polymorphism (SNP) of ercc1 at codon 118 has been proposed to impair ercc1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum-based chemotherapy. The primary aim of the present study was to evaluate ERCC1 expression and ercc1 codon 118 polymorphism in epithelial ovarian cancer (EOC) and their possible predictive value in patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tissue sections from 159 patients with advanced EOC were used for immunohistochemistry. Ercc1 codon 118 SNP genotyping was performed by real-time polymerase chain reaction. ERCC1 protein overexpression was found in 37.7% of the tumors. The CA-125 response rate was 94.5% (52/55) in patients with ERCC1-negative tumors compared to 80% (36/45) in patients with ERCC1-positive tumors (P = 0.026, chi(2)). The T/T genotype (44%) signalized a better response to chemotherapy than C/C (15%) + C/T (41%) variants (P = 0.045, trend test). Patients with ERCC1-negative tumors appear to have significantly better response to platinum-based chemotherapy compared to patients with ERCC1-positive tumors, but the differences in response rates did not translate into differences in survival. In addition, the TT genotype seems to be favorable toward better response to platinum-based chemotherapy.
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