There is no evidence to support the use of NER ERCC1C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC.
These findings suggest that ERCC1C118T 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.
Retrospective, unplanned analysis of excision repair cross complementation group 1 (ERCC1) and betatubulin III upregulation demonstrated poorer outcome in NSCLC patients treated with platinum-doublets and vinorelbine-based chemotherapy, respectively.
Current evidence strongly indicated the prospect of ERCC1C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients.
To the authors' knowledge, this is the first prospective study to date in patients with advanced NSCLC describing predictive germline polymorphisms not only for the clinical activity of PG chemotherapy (ERCC1, XPD10) but also for its toxicity (GSTP1, RECQ1, CDA).
Patients who had nonsmall cell lung cancer (NSCLC) with extranodal metastatic disease and an Eastern Cooperative Oncology Group performance status of 0/1 were accrued to 4 phase 2 clinical trials conducted at the H. Lee Moffitt Cancer Center: Trial A (first-line carboplatin/gemcitabine followed by docetaxel), Trial B (docetaxel and gefitinib in patients aged ≥70 years), Trial C (combination therapy with carboplatin/paclitaxel/atrasentan), and Trial D (personalized therapy based on ERCC1 and RRM1 expression).
Multivariate Cox regression analysis showed that ERCC1rs11615 AA genotype (P = 0.020) and smoking (p = 0.037) were associated with increased risks of death in early stage NSCLC patients after surgery.
Present data indicates that ERCC1118 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.
Our meta-analysis indicates that the ERCC1 Asn118Asn and C8092A polymorphisms may not be good prognostic biomarkers for platinum-based chemotherapy in patients with stage III-IV NSCLC.
We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real-Time PCR System, using genomic DNA extracted from blood samples.
We investigated whether ERCC1 (19007C>T) and RRM1 (-37C>A) polymorphisms impact response to chemotherapy and survival in 62 patients with NSCLC treated with platinum and gemcitabine.
Our results showed the ERCC1 118 T/T(HR=1.65, 95% CI=1.17-2.43) and XPD 751 Gln/ Gln genotypes (HR=1.52, 95%CI=1.04-2.08) were associated with an increased risk of death from NSCLC.
We investigated the association of three DNA repair gene polymorphisms - Asn118Asn in ERCC1 (rs11615), Lys751Gln in ERCC2 (rs13181), and Asp1104His in ERCC5 (rs17655) - with the progression-free survival of 85 patients treated with platinum-based chemotherapy after surgery for NSCLC.
We investigated the ERCC1 polymorphisms (C8092A and C118T) whether these factors influence for the prognosis of these 90 NSCLC patients treated with platinum-based chemotherapy.
The ERCC1T19007C and C8092A single nucleotide polymorphisms (SNPs) were evaluated in 122 Japanese non-small cell lung cancer (NSCLC) patients who underwent a complete resection and analyzed the clinicopathological significance of these SNPs.
Our results indicate that SNPs in the NER genes ERCC1 (Asn118Asn, 15310G>C, 8902G>T), XPA (-4G>A), ERCC2/XPD (Lys751Gln) and ERCC5/XPD (His46His); the BER genes APE1/APEX (Ile64Val), OGG1 (Ser326Cys), PCNA (1876A>G) and XRCC1 (Arg194Trp, Arg280His, Arg399Gln); and the DSB-R genes ATR (Thr211Met), NBS1 (Glu185Gln), XRCC2 (Arg188His) and XRCC9 (Thr297Ile) modulate NSCLC risk.
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.
Uncommon TT genotype of ERCC1 19007 T>C polymorphism could predict poor response and shortening of progression free survival in NSCLC patients treated with platinum-based I-line chemotherapy.
Lack of correlation between ERCC1 (C8092A) single nucleotide polymorphism and efficacy/toxicity of platinum based chemotherapy in Chinese patients with advanced non-small cell lung cancer.
Predictive value of ERCC1 and XPD polymorphism in patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a systematic review and meta-analysis.
The purpose of this study was to assess the predictive role of particular single nucleotide polymorphisms (SNPs) in the promoter regions of TOP2A and ERCC1 genes in non-small cell lung cancer patients (NSCLC) treated with chemotherapy.