Author of

• 30601

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  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Now Available
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30647

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    P2.01-44 - Promoter Polymorphisms of TOP2A and ERCC1 Genes as Predictive Factors for Chemotherapy in Non-Small Cell Lung Cancer Patients (Now Available) (ID 654)

    10:15 - 18:15  |  Presenting Author(s): Justyna Błach
    • Abstract
    • Slides

    Background
    

    TOP2A is an enzyme that control topologic changes in DNA during transcription and replication. ERCC1 is an enzyme takes part in DNA repair processes. Purpose of our studies was to assess predictive role of particular single nucleotide polymorphisms (SNPs) in promoter regions of TOP2A and ERCC1 genes in non-small cell lung cancer patients (NSCLC) treated with chemotherapy.

    Method
    

    We enrolled 116 NSCLC patients qualified to first line chemotherapy. Information on the chemotherapy regimens was available in 106 patients. All chemotherapy regimens were based on platinum compounds. 66 (62%) patients received additionally inhibitors of cell divisions (vinorelbine, taxanes). 40 (38%) patients were treated with nucleoside analogs or antimetabolites (gemcytabine, pemetrexed). DNA was isolated from whole blood with Qiamp DNA Blood Mini kit (Qiagen, Germany) according to the manufacture’s instruction. We examined five SNPs: rs11615 (ERCC1), rs3212986 (CD3EAP), rs13695 (TOP2A), rs34300454 (TOP2A), rs11540720 (TOP2A). Quantitative PCR using TaqMan probe (ThermoFisher, USA) was performed on Eco Illumina Real-Time PCR system device (Illumina Inc., USA). Statistical analysis were performed with MedCalc and Statistica 13.1 softwares.

    Result
    

    In whole group of patients, median of progression free survival (PFS) was 3 months. Patients with CC genotype in rs34300454 had significantly higher median PFS (8 months) compared to patients with CT genotype (4 months, p=0.0026; HR=0.36 with 95% CI: 0,19 to 0,7). We did not detect patients with TT genotype of this SNP. However, the differences in median PFS between patients with different genotypes of the TOP2A gene were significant only in the group receiving inhibitors of cell divisions (p=0.011). In second group of patients, we did not observed such significant relationship. Control of disease (response to chemotherapy or stable disease) were observed insignificantly more often in patients with AA genotype in rs11615 of ERCC1 gene than in patients with AG genotype of this SNP (X²=3.453, p=0.063).

    Conclusion
    

    Polymorphism of TOP2A gene could influence PFS in NSCLC patients treated witch chemotherapy and CC genotype of this polymorphism may be a good predictive factor for chemotherapy regimens containing cell division inhibitors.

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