Predictive Effects of ERCC1 and XRCC3 SNP on Efficacy of Platinum-based Chemotherapy in Advanced NSCLC Patients

• Published in: Japanese journal of clinical oncology 2010-10, Vol.40 (10), p.954-960
• Main Authors: Zhou, Caicun, Ren, Shengxiang, Zhou, Songwen, Zhang, Ling, Su, Cunxia, Zhang, Zengli, Deng, Qinfang, Zhang, Jie
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Base Sequence; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; chemotherapy; Cisplatin - administration & dosage; DNA repair gene; DNA-Binding Proteins - genetics; Endonucleases - genetics; excision repair cross-complementing group 1; Female; Gene Frequency; Genotype; Humans; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; non-small cell lung cancer; Polymorphism, Single Nucleotide; polymorphisms; Prognosis; Regression Analysis; Treatment Outcome; X-ray repair cross-complementing group 3
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyq071

Objective The purpose of the study was to investigate whether single-nucleotide polymorphisms of deoxyribonucleic acid repair gene excision repair cross-complementing group 1 at codon 118 and X-ray repair cross-complementing group 3 at codon 241 affected clinical outcomes in advanced non-small cell lung cancer patients receiving first-line platinum-based chemotherapy. Methods A total of 130 patients treated with platinum-based doublets were examined for genotyping of excision repair cross-complementing group 1 118 and X-ray repair cross-complementing group 3 241 in peripheral blood lymphocytes with the method of the TaqMan assay plus the real-time polymerase chain reaction method. Multivariate logistic or Cox's regression analyses were used to adjust for possible confounding variables. Results There were no differences in clinical characteristics among the different single-nucleotide polymorphisms. Overall response rate in the 130 patients was 20% with 85.4% of disease control rate. Followed up to 31 March 2008, there were 47 patients still alive. Overall survival was 15 months. No relationship was found between excision repair cross-complementing group 1 or X-ray repair cross-complementing group 3 single-nucleotide polymorphisms and tumor response to platinum-based chemotherapy. A significant correlation was found between excision repair cross-complementing group 1 118C/T single-nucleotide polymorphisms and survival (P = 0.003). In the multivariate model, the survival was highly related with excision repair cross-complementing group 1 118 C/T or T/T genotypes and tumor response to chemotherapy. Conclusions Overall survival was significantly improved in the patients with excision repair cross-complementing group 1 118 T/T or C/T treated by platinum-based chemotherapy.