BACKGROUND: Single nucleotide polymorphism (SNP) in DNA repair genes can be used to explain the differences in survival of platinum-treated non-small cell lung cancer (NSCLC) patients regardless of their performance status. To define the role of DNA repair gene SNPs in NSCLC patients, we investigated the association between survival and 12 different SNPs of 9 DNA repair genes. METHODS: 340 patients were treated with platinum-based chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probe, using genomic DNA extracted from peripheral blood samples. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS: The median overall survival time was 15 months and it was significantly longer in patients harboring ERCC1 118 C/T or T/T allele: 18 months as compared to 13.8 months for the C/C allele (P=0.014). Subgroup analysis revealed that ERCC1 118 C/T or T/T was associated with increased survival in elderly patients (P=0.018), male (P=0.022), squamous carcinoma (P=0.003), smoker (P=0.076) and those treated with non-gemcitabine/cisplatin or carboplatin (non-GP/GC) regimen (P=0.023). XRCC3C/C was associated with better survival in non-gemcitabine/cisplatin treated patients (P=0.014). Both of CCNH-V270A C/C or C/T and XPD 751 A/A showed a significant longer survival in the squamous cell carcinoma subgroup (P=0.047 and P=0.034 respectively). CONCLUSION: Present data indicates that ERCC1 118 C/T or T/T might provide a better prognostic predictive marker of NSCLC patients treated with platinum-based chemotherapy, mainly in elderly subgroup, male, squamous carcinoma, smoker and those treated with non-GP/GC regimen.
BACKGROUND: Single nucleotide polymorphism (SNP) in DNA repair genes can be used to explain the differences in survival of platinum-treated non-small cell lung cancer (NSCLC) patients regardless of their performance status. To define the role of DNA repair gene SNPs in NSCLCpatients, we investigated the association between survival and 12 different SNPs of 9 DNA repair genes. METHODS: 340 patients were treated with platinum-based chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probe, using genomic DNA extracted from peripheral blood samples. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS: The median overall survival time was 15 months and it was significantly longer in patients harboring ERCC1118 C/T or T/T allele: 18 months as compared to 13.8 months for the C/C allele (P=0.014). Subgroup analysis revealed that ERCC1118 C/T or T/T was associated with increased survival in elderly patients (P=0.018), male (P=0.022), squamous carcinoma (P=0.003), smoker (P=0.076) and those treated with non-gemcitabine/cisplatin or carboplatin (non-GP/GC) regimen (P=0.023). XRCC3C/C was associated with better survival in non-gemcitabine/cisplatin treated patients (P=0.014). Both of CCNH-V270A C/C or C/T and XPD 751 A/A showed a significant longer survival in the squamous cell carcinoma subgroup (P=0.047 and P=0.034 respectively). CONCLUSION: Present data indicates that ERCC1118 C/T or T/T might provide a better prognostic predictive marker of NSCLCpatients treated with platinum-based chemotherapy, mainly in elderly subgroup, male, squamous carcinoma, smoker and those treated with non-GP/GC regimen.
Authors: William D Figg; Cindy H Chau; Ravi A Madan; James L Gulley; Rui Gao; Tristan M Sissung; Shawn Spencer; Melony Beatson; Jeanny Aragon-Ching; Seth M Steinberg; William L Dahut Journal: Clin Genitourin Cancer Date: 2013-05-17 Impact factor: 2.872