Background
Topoisomerase 2-alpha (TOP2A) is an enzyme that controls topologic changes in DNA during transcription and replication. ERCC1 is an enzyme that takes part in DNA repair processes. The
Conclusions
Polymorphisms of the TOP2A and ERCC1 genes may be a predictive factor of toxicities and survival for chemotherapy in NSCLC patients.
Methods
We enrolled 113 NSCLC patients treated in the first line with platinum-based chemotherapy. Effectiveness was available for 71 patients. DNA was isolated from whole blood using the Qiamp DNA Blood Mini kit (Qiagen). We examined five SNPs: rs11615 (ERCC1), rs3212986 (ERCC1), rs13695 (TOP2A), rs34300454 (TOP2A), rs11540720 (TOP2A). Quantitative PCR using the TaqMan probe (ThermoFisher) was performed on a Eco Illumina Real-Time PCR system device (Illumina Inc).
Results
Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly longer median progression free survival (PFS) (8.5 months; P = .0088). Patients with the C/C genotype in rs3212986 of the ERCC1 gene had longer median PFS (7 months; P = .05). Patients with the C/C genotype in rs34300454 of TOP2A gene had significantly higher median PFS (7.5 months; P = .0029). Carriers of the C/C genotype in rs34300454 of the TOP2A gene had significantly longer median OS (15.5 months; P = .0017). Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly higher risk of neutropenia (P = .0133). Conclusions: Polymorphisms of the TOP2A and ERCC1 genes may be a predictive factor of toxicities and survival for chemotherapy in NSCLC patients.