title: Association of ERCC1-C118T and -C8092A polymorphisms with lung cancer risk and survival of advanced-stage non-small cell lung cancer patients receiving platinum-based chemotherapy: a pooled analysis based on 39 reports.
abstract: The published data on the predictive role of ERCC1 polymorphisms in lung cancer risk and survival of patients with advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy remains inconsistent. The aim of this meta-analysis was to determine the role of ERCC1 gene polymorphisms (C118T and C8092A) in this clinical situation. Eligible studies were included and assessed for quality using multiple search strategies. Thirty-nine published papers involving 9615 cases (4606 with Stage III/IV disease) and 5542 controls were included in the analysis. Pooled odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate risk. ERCC1-C118T was associated with lung cancer risk. The OR was 0.90 (95% CI: 0.81-0.99, p=0.043) in an additive genetic model (C allele vs. T allele) and 0.77 (95% CI: 0.63-0.95, p=0.013) in a recessive genetic model (CC/CT vs. TT). The corresponding risk was 0.74 (95% CI: 0.58-0.94, p=0.013) based on a homozygous comparison (CC vs. TT). No significant correlation was found for ERCC1 C8092A and there was no obvious relationship between ERCC1 C118T/C8092A polymorphisms and objective response to platinum-based chemotherapy. Overall survival (OS) of patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy was significantly related to ERCC1 C118T (HR: 1.29, 95% CI: 1.07-1.56, p=0.007, CT/TT vs. CC). There was no relationship between ERCC1 C8092A and survival (HR: 1.32, 95% CI: 0.84-2.10, p=0.23, CA/AA vs. CC). These findings suggest that ERCC1 C118T polymorphisms may serve as a biomarker for lung cancer risk and have prognostic value in patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based treatment. Further studies with larger numbers of subjects from a worldwide arena are needed to validate the associations.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, People's Republic of China.
authors.forename: Tong-Peng
authors.initials: TP
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.forename: Ling-Xiang
authors.initials: LX
authors.lastname: Liu
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Shu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D016017:Odds Ratio; D010984:Platinum / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias; D012306:Risk; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: 95% CI; 95% confidence interval; CR; Chemotherapy; ERCC1; HR; HWE; Hardy–Weinberg equilibrium; Meta-analysis; OR; OS; PD; PR; Platinum; Prognosis; Risk; SD; SNP; complete response; excision repair cross-complementing group 1; hazards ratios; odds ratio; overall survival; partial response; progressive disease; single nucleotide polymorphism; stable disease