XRCC1 Polymorphisms and Pancreatic Cancer:A Meta-Analysis

Objective：To assess the association between X-ray repair cross-complementating group 1 （XRCC1） polymorphisms and pancreatic cancer.Methods：We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.Results：Four studies with 1343 cases and 2302 controls were included.Our analysis found：at codon 194,the Trp allele did not decrease pancreatic cancer risk （Arg/Arg versus Trp/Trp：OR=0.97;95% CI：0.48-1.96;P=0.97;Arg/Arg versus Arg/Trp：OR=0.89;95% CI：0.70-1.13;P=0.55;Arg/Trp versus Trp/Trp：OR=1.06;95% CI：0.52-2.16;P=0.90）;at codon 280,only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk;at codon 399,the Gln allele also showed no signi？cant effect on pancreatic cancer compared to Arg allele （Arg/Arg versus Gln/Gln：OR=0.94;95% CI：0.74-1.18;Arg/Arg versus Arg/Gln：OR=0.97;95% CI：0.83-1.13;Arg/Gln versus Gln/Gln：OR=0.97;95% CI：0.77-1.22）.The shape of the funnel plot and the Egger＇s test did not detect any publication bias.Conclusion：There is no evidence that XRCC1 polymorphisms （Arg194Trp,Arg280His,and Arg399Gln） are associated with pancreatic cancer risk.

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer

Aim： This study explored the correlation between the expression of excision repair cross-complementation group 1 （ERCC1） and the prognosis of gastric cancer patients. Methods： From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry （IHC） was used to assess the expression of ERCCI in resected samples. The relationship between ERCCI expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time （MST） and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. Results： ERCC1 expression was positive in 412 patients （68.1%）. There is no significant difference between ERCCl-positive group and ERCCl-negative group in terms of the MST and 5-year survival rate （P=0.455）. The MST and 5-year survival rate have no significant difference （P=0.162） between group with chemotherapy and group with no chemotherapy in patients with ERCCl-positive expression. However, the MST and 5-year survival rate in patients with ERCCl-negative expression benefited more from with chemotherapy （P=0.019）. The ERCCl-positive patients survived longer than those ERCCl-negative patients （P=0.183） in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC 1 expression had no significant relationship with overall survival in patients with stage II or llI gastric cancer （P〉0.05）. Conclusions： ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCCl-negative expression could benefit more from adjuvant chemotherapy.

ERCC1 Asn118Asn polymorphism as predictor for cancer response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

Objective： To assess whether the polymorphism of ERCC1 Asn118Asn （C → T） had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. Methods： ERCC1 Asn 118Asn polymorphism was analyzed in 99 patients with stages Ⅲ and Ⅳ advanced colorectal cancer treated with oxaliplatin-based chemotherapy, For all of the patients, ERCC1 Asnl18Asn genotype was analyzed for associations with treatment response and time to disease progress （TTP）. Results： The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% （50/99）, C/T 41.41% （41/99）, T/T 8.08% （8/99）, respectively. Patients with C/C genotype showed higher response rate than those with C/T ＋ T/T （OR = 3.764, 95% CI： 1.310-10.813）. The median TTP of all patients was 7 months （95% CI： 5.569--8.431）. Patients with C/C genotype showed a median TTP of 10 months （95% CI： 8.924-11.076）, which was longer than 5 months （95% CI： 4.424-5.576） in patients with C/T ＋ T/T genotypes. Conclusion： Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn 118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.

Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods：A thorough literature search using PubMed （Medline）,Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios （HRs） or odds ratios （ORs） with 95% confidence intervals （CIs） were calculated to estimate the results.Results：A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival （OS） （HR =2.325,95% CI：1.720-3.143,P 〈 0.001）,progression-free survival （PFS） （HR =1.917,95% CI：1.366-2.691,P 〈 0.001） and poor response to chemotherapy （OR =0.491,95% CI：0.243-0.990,P =0.047）.Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions：ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1＇s prognostic value.

宫颈鳞癌中ERCC1甲基化与顺铂为基础同期放化疗敏感性关系研究

目的：探讨核苷酸切除修复交叉互补基因1（ ERCC1）甲基化状态与宫颈鳞癌患者以顺铂为基础同期放化疗敏感性关系及与临床病理特征的关系。方法采用甲基化特异性PCR法检测20例正常宫颈组织和60例宫颈鳞癌组织中ERCC1基因甲基化状态，宫颈鳞癌患者均接受以顺铂为基础同期放化疗。按照RECIST标准评价疗效，根据疗效结果将CR定为放化疗敏感组， PR＋SD＋PD为放化疗抗拒组。采用χ2检验比较两组间ERCC1基因甲基化状态差异，采用Logistic多元回归进行多因素分析ERCC1基因甲基化状态与各临床病理特征的关系和放化疗敏感性的相关性。结果宫颈鳞癌组织中 ERCC1甲基化概率为60％，高于正常宫颈组织0％（ P＝0.000）。多因素分析显示ERCC1甲基化是影响宫颈鳞癌以顺铂为基础的同期放化疗敏感性因素（ P＝0.022）；ERCC1基因甲基化与宫颈鳞癌患者组织学分级具有相关性（ P＝0.030），与患者年龄、肿瘤大小、淋巴结转移、FIGO分期、治疗前血红蛋白及血小板计数等临床病理特征关系差异均相近（ P＝0.729、0.707、0.340、0.747、0.073、1？000）。结论 ERCC1基因启动区甲基化状态可能参与宫颈鳞癌的发生发展，可能影响宫颈鳞癌以顺铂为基础同期放化疗敏感性，可能参与了细胞分化过程。

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT） （41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.