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X. Zhang



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-043 - CYP1A1*2A Polymorphism is correlate with EGFR Exon 19 Mutation and is an Independent Prognostic indicator for the Advanced Lung Cancer Patients Treated with EGFR-TKI (ID 3053)

      09:30 - 09:30  |  Author(s): X. Zhang

      • Abstract

      Background
      The EGFR mutated status becomes a very important factor for NSCLC patients considering of the treatment, but the mechanism of the mutation is still unknown.Our study aimed to detect the correlations among EGFR mutations and polymorphisms of EGFR and CYP1A1 genes and their associations with clinical outcome of NSCLC patients treated with EGFR-TKI.

      Methods
      We evaluated the EGFR mutations, the genotypes for EGFR Intron1 (CA) n, R497K and CYP1A1 *2A, *2C polymorphisms in 70 Chinese patients with NSCLC. Genetic polymorphisms were correlated to EGFR mutations. As to subgroup of 36 patients who accepted the EGFR-TKI treatment and had systemic 5 years follow up data, the associations among the somatic EGFR mutations, the genomic polymorphisms of EGFR and CYP1A1 and clinical outcome of the EGFR-TKI were analyzed.

      Results
      The data show that EGFR Intron1 (CA) n and CYP1A1*2A, *2C polymorphisms were correlated with EGFR mutations (P=0.006, P=0.001, and P=0.008, respectively) and all the three polymorphisms were also associated with EGFR 19 exon delection (P=0.007, P=0.033, and P=0.006, respectively); whereas the multivariate analysis demonstrated that only CYP1A1*2A polymorphism was associated with EGFR somatic mutations (P=0.021). For 36 patients treated with EGFR-TKI, the EGFR mutation and CYP1A1*2A polymorphism showed correlation with clinical response of EGFR-TKI(P=0.001, and P=0.011, respectively); However, the multivariate analysis confirmed that the EGFR mutation is still the most effective predictive factor (P=0.006) ; Either the log-rank test and Cox regression analysis demonstrated that the CYP1A1*2A polymorphism is independent prognostic factor for patients’ overall survival treated with EGFR-TKI( P=0.000 for both statistical analysis).

      Conclusion
      The results demonstrate that the CYP1A1*2A polymorphism is correlated with EGFR somatic mutation; for advanced NSCLC patients with EGFR-TKI therapy, the EGFR mutation status is still most effective predictor for clinical response of EGFR-TKI, whereas the CYP1A1*2A polymorphism is an independent prognostic factor. The inner mechanisms deserve thorough study.