Excision Repair Cross-complementation Group 1 Polymorphisms Research Articles

Polymorphisms in ERCC1, ERCC4 and ERCC5 genes as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers

BackgroundOccupational pesticides exposure has raised health concerns due to genotoxicity and accumulation of DNA damage. Polymorphisms in genes encoding enzymes involved in nucleotide excision repair (NER) may affect the individual’s susceptibility to pesticide toxicity.MethodsThis study evaluates the association of excision repair cross complementation group 1 (ERCC1) (8092 C > A, 3’UTR, rs3212986) and ERCC1 (19007 C > T, Asn118Asn, rs11615), ERCC4 (1244 G > A, Arg415Gln, rs1800067) and ERCC5 (3507 G > C, Asp1104His, rs17655) polymorphisms with pesticide-induced DNA damage in North-West Indian agricultural workers. The study population comprised 225 agricultural workers exposed to pesticides and 225 non-exposed controls.ResultsOur study demonstrate that exposed workers carrying variant ERCC1 8092AA genotype showed higher total comet DNA migration (p = 0.015) as well as increased frequency of cells showing DNA migration (p = 0.027). Exposed agricultural workers with variant ERCC4 1244AA (415Gln/Gln) and ERCC5 3507CC (1104His/His) genotypes exhibited elevation in total comet DNA migration (p < 0.01). However, genotypes of ERCC1 19007 C > T (Asn118Asn) showed no association with total comet DNA migration (p = 0.963), frequency of cells showing DNA migration (p = 0.423) as well as mean tail length (p = 0.432).ConclusionERCC1, ERCC4 and ERCC5 polymorphisms influence DNA damage and can be used as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.

The Relationship between Single Nucleotide Polymorphism of ERCC1 Gene and the Response to Platinum Based Chemotherapy in Egyptian Non-Small Cell Lung Cancer Patients

Abstract Background Lung cancer (LC) is the second most common cancer diagnosed in both males and females. There are two subtypes of LC. Non-small cell lung cancer (NSCLC) is the major one. Treatment options for NSCLC depends mainly on the stage at diagnosis. The majority of the patients are diagnosed at advanced stages at time of presentation. Therefore, chemotherapy and radiotherapy play the dominant role in treatment of advanced NSCLC. The most commonly used chemotherapy is platinum-based chemotherapy as cisplatin and carboplatin and third generation drugs as vinorelbine and gemcitabine. The efficacy of platinum-based chemotherapy is limited by chemoresistance. The excision repair cross complementation group 1(ERCC1) gene is a member of nucleotide excision repair pathway that plays a critical role in the DNA repair by removing DNA covalent helix-distorting adducts. Aim of the Work In this study investigated the relationship between single nucleotide polymorphism of ERCC1 rs11615 and the response to platinum-based chemotherapy in Egyptian NSCLC patients in order to prevent the non-necessary exposure to the toxic effect of chemotherapy. Patients and Methods This is a cross-sectional study conducted on 50 NSCLC patients who were recruited from the Oncology Clinic in Ain Shams University Hospitals; twenty of them were responders to platinumbased chemotherapy and the other 30 were non-responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the ERCC1 (T/C) polymorphism by realtime PCR was done for both the responders' and the non-responders' groups. Results There was no significant statistical difference observed between the responders’ and nonresponders’ groups regarding the genotype frequencies nor the allelic frequency (p &amp;gt; 0.05). Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies nor the allelic frequencies of the ERCC1 rs 11615 among the responders' and the non-responders' groups. Further studies with higher sample size are needed to clarify the association.

Effect of ERCC1 polymorphisms on the response to platinum-based chemotherapy: A systematic review and meta-analysis based on Asian population.

Platinum-based chemotherapy is one of the most common treatments for many cancers; however, the effect of chemotherapy varies from individual to individual. Excision repair cross complementation group 1 (ERCC1) is widely recognized as a key gene regulating nucleotide excision repair (NER) and is closely associated with platinum response. Many studies have yielded conflicting results regarding whether ERCC1 polymorphisms can affect the response to platinum and overall survival (OS). Therefore, it is necessary to perform a meta-analysis of patients with specific races and cancer types. Eight databases (EMBASE, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Scopus, VIP, China Biology Medicine disc and Wanfang databases) were searched. Results were expressed in terms of odds ratios (ORs), hazard ratios (HRs) and 95% CIs. In this study, rs11615, rs2298881 and rs3212986 SNPs were studied. In the comparison between CT and TT on the response to platinum, esophageal cancer [I2 = 0%, OR = 6.18, 95% CI(1.89,20.23), P = 0.003] and ovarian cancer [I2 = 0%, OR = 4.94, 95% CI(2.21,11.04), P<0.001] showed that the rs11615 CT genotype predicted a better response. In the comparison between CC and TT, ovarian cancer [I2 = 48.0%, OR = 6.15, 95% CI (2.56,14.29), P<0.001] indicated that the CC genotype predicted a better response. In the meta-analysis of OS, the CC genotype was related to longer OS than TT in ovarian cancer [TT vs CC: I2 = 57.7%, HR = 1.71, 95% CI (1.18, 2.49), P<0.001]. The ERCC1 rs11615 polymorphism was related to the response to platinum and OS, but the correlation is based on specific cancer types in the Asian population.

Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.

Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.

Perspectives of ERCC1 in early-stage and advanced cervical cancer: From experiments to clinical applications.

Cervical cancer is a public health problem of extensive clinical importance. Excision repair cross-complementation group 1 (ERCC1) was found to be a promising biomarker of cervical cancer over the years. At present, there is no relevant review article that summarizes such evidence. In this review, nineteen eligible studies were included for evaluation and data extraction. Based on the data from clinical and experimental studies, ERCC1 plays a key role in the progression of carcinoma of the uterine cervix and the therapeutic response of chemoradiotherapy. The majority of the included studies (13/19, 68%) suggested that ERCC1 played a pro-oncogenic role in both early-stage and advanced cervical cancer. High expression of ERCC1 was found to be associated with the poor survival rates of the patients. ERCC1 polymorphism analyses demonstrated that ERCC1 might be a useful tool for predicting the risk of cervical cancer and the treatment-related toxicities. Experimental studies indicated that the biological effects exerted by ERCC1 in cervical cancer might be mediated by its associated genes and affected signaling pathways (i.e., XPF, TUBB3, and. To move towards clinical applications by targeting ERCC1 in cervical cancer, more clinical, in-vitro, and in-vivo investigations are still warranted in the future.

Modulation of DNA damage by XPF, XPG and ERCC1 gene polymorphisms in pesticide-exposed agricultural workers of Punjab, North-West India

Inter-individual variations in DNA repair capacity (DRC) for repairing pesticide-induced DNA oxidation damage may influence adverse health outcomes. We aimed to evaluate whether polymorphisms in genes involved in nucleotide excision repair (NER) pathway could modulate DNA damage in pesticide-exposed agricultural workers. Xeroderma pigmentosum group F (XPF) (Arg415Gln, G1244A, rs1800067), xeroderma pigmentosum group G (XPG) (Asp1104His, G3507C, rs17655), excision repair cross complementation group 1 (ERCC1) (3′UTR, C8092A, rs3212986) and ERCC1 (Asn118Asn, C19007T, rs11615) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 225 pesticide-exposed agricultural workers and 225 controls from Punjab, North-West India. The assessment of DNA damage was carried out by alkaline comet assay. Kruskal-Wallis test was used to evaluate the association of gene polymorphisms in NER pathway with DNA damage. Pesticide-exposed agricultural workers carrying variant XPF Gln/Gln (AA) genotype showed higher comet tail length (p < 0.01) than wild type Arg/Arg (GG) genotype. The comet tail length (p < 0.01) was found to be significantly increased in exposed agricultural workers carrying XPG His/His (CC) genotype than wild-type Asp/Asp (GG) genotype. In relation to the individuals carrying wild type ERCC1 3′UTR CC genotype, exposed individuals with variant ERCC1 3′UTR CA genotype showed elevation in the comet tail length (p = 0.029). However, we found no association of ERCC1 Asn118Asn (C19007T) genotype with DNA damage. These results indicate that XPF, XPG and ERCC1 genes of NER pathway may modulate the efficacy of the DNA repair system against pesticide exposure in our population.

Expression and Genetic Polymorphisms of ERCC1 in Chinese Han Patients with Oral Squamous Cell Carcinoma.

The aim of this study was to investigate the expression of the excision repair cross-complementation group 1 (ERCC1) in oral squamous cell carcinoma (OSCC) and the possible association of ERCC1 polymorphisms with susceptibility and response to chemotherapy of OSCC in a Chinese Han population. The expression of ERCC1 was determined by real-time PCR in eight patients. Four single-nucleotide polymorphisms (SNPs) rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were genotyped in 113 OSCC patients and 184 healthy controls using a PCR restriction matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) assay. We found that a higher gene expression of ERCC1 was observed in tumor tissue as compared to pericarcinomatous tissue in OSCC patients. All genotypic and allelic frequencies of the tested ERCC1 polymorphisms were in Hardy-Weinberg equilibrium. The genotypic and allelic frequencies of rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were not different between OSCC patients and controls. No correlation was observed between ERCC1 polymorphisms and the response to chemotherapy. Our results show that ERCC1 is increased in the tumor tissue of OSCC patients. The investigated ERCC1 gene polymorphisms (rs11615, rs3212948, rs3212961, and rs735482) are not associated with the susceptibility and response to chemotherapy of OSCC in our investigated Chinese Han population.

Role of common ERCC1 polymorphisms in cisplatin-resistant epithelial ovarian cancer patients: A study in Chinese cohort.

Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum-based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross-complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum-based chemotherapy in Chinese EOC patients. Patients (n=559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty-three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross-complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum-based chemotherapy outcomes.

Predictive Value of Excision Repair Cross-Complementation Group 1 in the Response to Platinum-Based Chemotherapy in Esophageal Cancer: A Meta-Analysis

Introduction: Platinum is widely used in the treatment of esophageal cancer. In clinical practice, it is significant to distinguish patients who respond to platinum from those who do not. Excision repair cross-complementation group 1 (ERCC1) is thought to be the key in the resistance to platinum. However, whether it is related to the platinum-based chemotherapy response on real esophageal cancer patients is controversial. We conducted this meta-analysis to explore the association between ERCC1 polymorphisms, its expression levels and platinum-based chemotherapy response, and identify the most sensitive genotypes. Methods: The study was carried out according to the Cochrane handbook for systemic reviews of intervention. The study protocol has been registered on PROSPERO. Results: Three studies were included in the analysis of C8092A polymorphisms, 5 in the C118T, and another 6 in ERCC1 expression levels. In C118T polymorphisms, compared to wild genotype, patients with mutant genotypes had a significantly higher response rate. As for C8092A polymorphisms, the mutant genotypes also presented a better response than the wild genotype. The pooled analysis indicated a significantly higher response rate in patients with a low expression of ERCC1. Conclusions: ERCC1 is a valuable biomarker for platinum-based chemotherapy in esophageal cancer. Patients with ERCC1 mutations or low-level ERCC1 expression are more sensitive to platinum-based chemotherapy.

ERCC1 and XRCC1 single nucleotide polymorphisms can guide treatment decision in patients with metastatic non-small cell lung cancer

Results from studies in several cancers on single nucleotide polymorphisms (SNPs) suggest that DNA repair capacity may have prognostic implication for disease recurrence, survival, and responses to treatment. This study aimed to evaluate the potential prognostic value of SNPs as biomarkers in patients with metastatic non-small cell lung cancer (mNSCLC) treated with platinum. Analysis of SNPs from peripheral blood cells was performed by 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 clinical and pathological parameters, and survival. The median progression-free survival (PFS) and overall survival (OS) of 145 patients were 5.1 months and 30.9 months, respectively. In the univariate analysis ERCC1 genotype, XRCC1 genotype, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were significant parameters for OS. In the multivariate analysis ERCC1 genotype, XRCC1 genotype, and ECOG-PS retained their significance. The median OS was 45.2 months for the ERCC1 normal (CC) and heterozygote (CT) genotypes, and 25.5 months for the ERCC1 mutant (TT) genotype. The median OS was 31.4 months for the XRCC1 normal (AA) and heterozygote (AG) genotypes, and 23.1 months for the XRCC1 mutant (GG) genotype. The median OS was 30,7 months for ECOG-PS≤ 1 and 10.2 months for ECOG-PS≥ 2. ERCC1 and XRCC1 genotypes, and ECOG-PS independently predicted OS in mNSCLC patients. Additional studies are needed for the further evaluation of potential prognostic SNPs in mNSCLC.

The role of ERCC1 and AFP gene polymorphism in hepatocellular carcinoma.

The aim of this study was to evaluate the effects of polymorphisms in excision repair cross-complementation group 1 (ERCC1) and alpha-fetoprotein (AFP) genes and their haplotypes on the susceptibility to hepatocellular carcinoma (HCC), and to decipher the association between single-nucleotide polymorphisms (SNPs) and clinicopathologic characteristics of HCC.Peripheral blood DNA was extracted from 206 subjects. SNaPshot technique was used for genotyping 5 SNP sites of the ERCC1 rs735482, rs1046282, rs3212948, and AFP rs737241, rs4024 genotypes. Chi-squared test and logistic regression model were used to analyze the relationship of different genotypes or haplotype and the susceptibility and clinicopathologic characteristics of HCC.The frequency of GG.GA and AA genotypes at the AFP rs737241 site in the case and control groups showed statistically significant differences (P < .05). The risk of HCC in subjects carrying mutated allele A (GA+AA) was increased by 0.543-times (P < .05) compared to that in the subjects with the GG genotype. Significant differences were observed in the linkage disequilibrium between 2 of the five SNPs (P < .05); the frequency of ERCC1 C-C and AFP A-A haplotypes was significantly lower in the case group than in the control group (P < .05). The results of clinicopathologic analysis showed that A allele at the rs737241 locus could increase the expression level of AFP (P = .007), the rs1046282 mutation C allele could increase the AFP expression level (P = .011), rs4024 locus mutation A allele could reduce the risk of vascular invasion (P = .013), rs3212948 locus mutation T allele could reduce the differentiation of liver cancer (P = .022), rs1046282 locus C allele could reduce the DNA load of hepatitis B virus (P = .035), and rs735482 A allele could increase the tumor size in HCC (P = .037).The SNPs in rs737241 for AFP gene may correlate with the occurrence of HCC. The SNPs in ERCC1 and AFP genes may affect the prognosis of HCC, offering reliable information for early prediction of tumor progression and diagnosis of HCC.

Excision repair cross-complementing group-1 (ERCC1) gene induction in peripheral blood mononuclear cells as a marker of outcome in patients with colorectal cancer treated with oxaliplatin.

542 Background: Oxaliplatin is a third generation platinum agent that confers tumoricidal effect by forming platinum-DNA adducts and is an integral part of the standard of care regimens for patients with colorectal cancer (CRC). Tissue resistance to oxaliplatin appears to be multifactorial, with the nucleotide excision repair (NER) pathway playing a major role. We have previously demonstrated that Excision Repair Cross-Complementing group-1 (ERCC1), can be induced in colorectal cell lines on exposure to Oxaliplatin and high levels confer resistance to apoptosis. We aim to further this knowledge by analyzing gene expression in vivo, using PBMC as a surrogate, to assess ERCC1 as a biomarker of sensitivity to Oxaliplatin therapy. Methods: Patients with CRC who received oxaliplatin were consented to blood (PBMC) sampling at 0, 2, 48 hours, and 14 days during any cycle of chemotherapy. ERCC1 gene expression was quantified by qPCR (quantitative real time polymerase chain reaction) and WB (western blotting). Clinical benefit from oxaliplatin was determined using the parameters of relapse free survival (RFS) for limited stage and progression free survival (PFS) for mCRC. Results: Fifty-four patients were enrolled on study, 25 (46.3%) had mCRC. Twenty-four patients were included in final analysis based on clinical data. Thirteen (52%) had an increase in ERCC expression from baseline, while 11 (48%) showed no change or decrease. Median PFS was 190 and 237 days respectively (log-rank test HR 2.35, CI 1.005-5.479; p = 0.0182). In the 29 patients with limited stage disease, 19 (65.5%) had an induction of ERCC. However, in these patients change in expression did not correlate with RFS. We did not find any significant correlation of PFS with baseline expression of ERCC1 in either group. Conclusions: We confirm our hypothesis that the ERCC1 gene is induced in vivo in a sub-population of patients on treatment with Oxaliplatin. This induction can serve as a potential marker of resistance to oxaliplatin based chemotherapy in mCRC as evidenced by the significant difference in PFS. Further analyses of the influence of ERCC1 polymorphisms on outcomes is underway.

Study of the Relationship between ERCC1 Polymorphisms and Response to Platinum-based Chemotherapy in Iranian Patients with Colorectal and Gastric Cancers.

This study was designed to evaluate the effect of excision repair cross complementing group 1 (ERCC1) rs11615 codon 118C/T gene polymorphisms on treatment outcomes in Iranian patients receiving oxaliplatin-based regimens for colorectal (CRC) and gastric cancers (GC). Patients, who were candidates to receive oxaliplatin-based chemotherapy, entered into the study. In 2-week intervals, the patients received combination regimen of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) for 3 months. ERCC1 rs11615 codon 118C/T polymorphism was tested by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method using patients’ peripheral blood lymphocytes. The tumor response to chemotherapy was evaluated by examining the size of the tumor using CT scan. Association between response rates, according to the RECIST criteria, and patients’ genotypes was evaluated. Any relationship between response rate and possible explanatory factors was also determined. Overall, 40 patients (13 females (32.5%), and 27 males (67.5%)) enrolled in the study. Four patients (10.0%) carried the homo­zygous mutation (T/T genotype), ten patients (25.0%) were heterozygous (C/T genotype), and twenty-six patients (65%) were homo­zygous (C/C genotype). Response rate were 30.77%, 20.00%, and 0.00% for the genotypes C/C, C/T, and T/T, respectively. No significant association between response rate and genotypes was observed (p = 0.64). Patients with well- and moderately-differentiated histological grade of the tumor showed a better response rate (100.00% of 2 patients and 66.66% of 12 patients, respectively) compared to those with poorly differentiated (0.00% of 26 patients) histological grade (p < 0.001). Further multicenter studies are recommended to confirm conclusively our findings.

PO534 Cost-Effectiveness Analysis of Therapeutic Hypothermia In Critical Patient After Cardiac Arrest: Estimate of Lifetime Horizon Follow-Up

Customized chemotherapy has several advantages: patients are more likely to be treated with the most effective agents and can be spared the toxicity of ineffective drugs. Based on the literature, excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) genes represent predictive biomarkers of response to platinum compound and gemcitabine, in NSCLC.We had planned a phase II trial (Simon design) to evaluate combination chemotherapy according to single nucleotide polymorphisms (SNPs) of ERCC1 (118T/C and 8092C/A) and RRM1 (−37C/A and −524T/C) in naïve patients affected by advanced NSCLC. ERCC1 and RRM1 SNPs assessment was performed in peripheral blood lymphocytes (PBLs). Combination chemotherapy was selected based on ERCC1 and RRM1 SNPs: we assume that patients with one or two C alleles at position 118 and with one or two A alleles at position 8092 in ERCC1 gene would correspond to Cisplatin non-responder and than with two A alleles at −37 and two C alleles at −524 in RRM1 gene to gemcitabine non-responder. Four schedules were provided: cisplatin + gemcitabine, cisplatin + docetaxel, gemcitabine + docetaxel; docetaxel + vinorelbine. Primary endpoint was overall response (ORR) in the intention-to-treat population.42 patients were enrolled from January 2010 to November 2011; 40 patients received at least 1 cycle of chemotherapy; median age was 66 years (range: 47–72); 36(90%) had stage IV, 4(10%) IIIB; 23(58%) had adenocarcinoma, 14(35%) squamous carcinoma. Twenty-five (62%) patients received treatment A, 3(8%) treatment B, 11(28%) treatment C, 1(23%) treatment D. ORR was 55%, analysis in squamous patients subgroups showed 71.4% ORR. The median follow-up was 19.7 months, PFS was 23 weeks (95% CI = 15–26) and OS was 40.4 weeks (95% CI = 32–55). Treatment was well tolerated.We observed an increase of ORR in NSCLC patients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status.

ERCC1 polymorphism predicts clinical outcomes of oxaliplatin-based chemotherapies in advanced colorectal cancer: A systemic review and metaanalysis

Objective: To systematically evaluate the precise role of the excision repair cross-complementing group 1 (ERCC1) polymorphism Asn118Asn (C19007T, rs11615) in curative effects and prognosis of patients with advanced colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy. Methods: Qualified studies were retrieved from databases including PubMed, EMBASE, Wanfang and CNKI until January 31st, 2015. Literature published in English and Chinese were selected for metaanalysis on relationship between ERCC1 polymorphism Asn118Asn and therapeutic effects and prognosis of advanced CRC patients receiving oxaliplatin-based chemotherapy. Data extracted from these articles included study ID, title, author, publication year, ethnicity, country, numbers of cases and controls, progression-free survival (PFS) and overall survival (OS). Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response with hazard ratios (HRs) using Stata software (version 11.0). Results: A total of 13 articles were included in the study. Overall, meta-analysis showed no significant correlation between the ERCC1 C118T polymorphism and objective response (OR=0.78; 95% CI for 0.29-2.07), PFS (HR=1.70, 95% CI=0.92-3.14) or OS (HR=1.69, 95% CI=0.91-3.14) in advanced CRC patients with oxaliplatin-based chemotherapy. Stratified analysis among Asian and Caucasian populations showed that the ERCC1 C118T polymorphism was not significantly correlated with objective response (OR=2.03 vs. 0.40; 95% CI=0.62-6.68 vs. 0.12-1.30), but was significantly correlated with PFS and OS. Moreover, Asian patients carrying T/T or T/C genotypes of ERCC1 C118T had significant shorter PFS (HR=2.41, 95% CI=1.86-3.11) and OS (HR=2.36, 95% CI=1.76-3.16). Conclusion: In patients with advanced CRC undergoing oxaliplatin-based chemotherapy, there is no correlation between ERCC1 Asn118Asn (C/T) gene polymorphism and therapeutic effects. Asian patients with T allele has shorter PFS and OS.

Meta-analysis showing that ERCC1 polymorphism is predictive of osteosarcoma prognosis.

To investigate correlations between excision repair cross-complementation group 1 (ERCC1) and 2 (ERCC2) polymorphisms and osteosarcoma prognosis, we conducted a meta-analysis of studies published through October 2016. Studies were identified in the PubMed, ScienceDirect, Springer, and Web of Science databases using preferred reporting items for systematic reviews and meta-analyses (PRISMA). Odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), tumor response (TR), and event-free survival (EFS) were estimated. Our meta-analysis included eleven studies in which four SNPs (ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and rs1799793) reportedly associated with osteosarcoma prognosis were investigated. Each of these studies scored > 6 on the Newcastle-Ottawa Scale (NOS). We found that only one SNP, ERCC1 rs11615, correlated with improved OS and TR. The HR of T vs. C for OS was 1.455 (T/C, 95% CI = 1.151–1.839, P = 0.002, I2 = 37.80%). The OR of T vs. C for good TR was 0.554 (T/C, 95% CI = 0.437–0.702, P < 0.001, I2 = 0%). Few significant outcome was observed in subgroup analyses stratified based on study characteristics with adjustments for potential confounders. Our results suggest that ERCC1 rs11615 CC is associated with a better clinical outcome. This suggests rs11615 may be a useful genetic marker for predicting osteosarcoma prognosis.

Association between the ERCC1 polymorphism and platinum-based chemotherapy effectiveness in ovarian cancer: a meta-analysis

BackgroundOvarian cancer is a prominent public health problem which affects people all around the world. Platinum-based chemotherapy is a common treatment for ovarian cancer, however, the effectiveness of chemotherapy varies from patient to patient. The excision repair cross complementation group 1 (ERCC1) protein may mediate chemotherapy resistance. A meta-analysis was conducted to explore whether platinum-based chemotherapy effectiveness could be attributed to the ERCC1 C19007T polymorphisms.MethodsSeven major databases (EMBASE, Web of Science, Pubmed, Springer Link, Chinese National Knowledge Infrastructure (CNKI), EBSCO and Science Direct databases) were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the results.ResultsIn this meta-analysis, 1169 subjects (425 non-responders and 744 responders) from 8 studies were included. The overall OR (C vs. T alleles) using random model was 1.07 (95% CI 0.75-1.52, P = 0.7), which was not statistically significant. Moreover, there was no significant difference in the analysis by race.ConclusionThere is no association between the ERCC1 C19007T polymorphism and platinum-based chemotherapy effectiveness in ovarian cancer. The polymorphism did not have a significant impact on platinum-based chemotherapy in non-responders and responders.

Biological and predictive role of ERCC1 polymorphisms in cancer.

Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.

Roles of XRCC1/XPD/ERCC1 Polymorphisms in Predicting Prognosis of Hepatocellular Carcinoma in Patients Receiving Transcatheter Arterial Chemoembolization.

To investigate the potential prognostic roles of polymorphisms in the X-ray repair cross-complementing group 1 (XPCC1), xeroderma pigmentosum group D (XPD) and excision repair cross-complementing group 1 (ERCC1) genes for patients with hepatocellular carcinoma (HCC) receiving transcatheter arterial chemoembolization (TACE). Clinical data and blood samples from 308 HCC patients receiving TACE were collected between January 2010 and December 2013. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) analyses was used to determine the genotypes of the XPCC1 (rs25487), XPD (rs13181) and ERCC1 (rs11615) genes. The relationships between the genotypes and the efficacy of TACE treatment were analyzed. The XRCCI rs25487 polymorphism was associated with a favorable prognosis in HCC patients receiving TACE (p = 0.006), and patients carrying variant genotypes (A/A + G/A) were associated with significantly reduced risk of death compared with those with the wild genotype (G/G) (HR = 0.556; 95% CI = 0.354-0.874). These findings were supported by Kaplan-Meier survival curve analysis showing that median survival time for patients with A/A + G/A genotypes was significantly longer compared with those with the G/G genotype (11.2 month vs. 8.0 months; log rank p = 0.006). Stratified analyses revealed that A/A + G/A genotypes of XRCC1 rs25487 are associated with significantly reduced risk of death compared with the G/G genotype in patients grouped by tumor size, portal vein tumor thrombus (PVTT), alpha-fetoprotein (AFP) and TNM stage (all p < 0.05). The ERCC1 rs13181 and XPD rs11615 polymorphisms were not predictive of clinical outcome for HCC patients receiving TACE (both p > 0.05). The XRCC1 rs25487 polymorphisms are prognostic for HCC patients receiving TACE. The ERCC1 and XPD polymorphisms had no relationship to the clinical outcomes.

Effect of the ERCC1 (C118T) Polymorphism on Treatment Response in Advanced Non-Small Cell Lung Cancer Patients Undergoing Platinum-Based Chemotherapy

For advanced non-small-cell lung cancer (NSCLC) cases, a platinum-based regimen is the first-line chemotherapy treatment. The excision repair cross-complementing group 1 (ERCC1) plays an important role in DNA repair and has been related to resistance to platinum chemotherapy. This study aimed to investigate the effects of the ERCC1 (C118T) polymorphism on treatment response in 26 Thai advanced NSCLC patients receiving first line platinum-based chemotherapy during January to July 2015 at King Chulalongkorn Memorial Hospital (KCMH). DNA was extracted from peripheral blood lymphocytes and the single nucleotide polymorphism of ERCC1 was genotyped using a real-time PCR method with the TaqMan assay. The distribution of C/C, C/T and T/T genotypes was 57.7 %, 34.6 % and 7.7 %, respectively. The response rate to platinum-based chemotherapy in the wild type (C/C) of ERCC1 (C118T) was better than with the variant types (C/T and T/T) but the difference was not statistically significant (29.7% vs 9.1%, P=0.274). The results showed that a genetic polymorphism in ERCC1 might influence patient response to platinum-based chemotherapy. Further multicenter studies are now required to confirm the results of our study.