Author of

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  P2.03b - Poster Session with Presenters Present (ID 465)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17681

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    P2.03b-052 - XRCC1 Arg399Gln and Rad51 G135C Gene Polymorphisms in Advanced  Lung Adenocarcinoma in Serbia (ID 4945)

    14:30 - 14:30  |  Author(s): D. Radosavljevic
    • Abstract
    • Slides

    Background:
    XRCC1 and Rad51 are proteins involved in DNA base excision repair and DNA homologous recombination/double-stranded-break repair mechanisms respectively. In non-small cell lung cancer, XRCC1 Arg399Gln polymorphism (disrupts protein-protein interactions), and Rad51 G135C polymorphism (enhances Rad51 promoter activity), have been proposed as factors that influence the overall and progression-free survival (OS and PFS) of patients treated with platinum-based chemotherapy. This study aimed to evaluate the influence of XRCC1 Arg399Gln and Rad51 G135C polymorphisms on the toxicity of chemotherapy and clinical outcome (OS, PFS) of advanced adenocarcinoma patients in Serbia.
    
    Methods:
    The study included 94 advanced lung adenocarcinoma patients, EGFR wild type, stage IIIB or IV (TNM7), performance status 0, 1 or 2, of Caucasian descent, who recieved standard platinum-based chemotherapy. XRCC1 and Rad51 genotyping was done by PCR-RFLP. Statistical analysis was performed using Chi-square, Fisher’s exact, Wilcoxon rank sum test, Breslow-Day test. Survival methodology was used for OS and PFS (Kaplan-Meier product limit method and Log-Rank test, Cox regression for HR). Statistical significance was considered for p<0.05.
    
    Results:
    The group consisted of 62 males (66%) and 32 females (34%), median age at diagnosis 61 years (range 37-84), with 77 (82 %) of current or ex-smokers, and 65 (66%) of which presented with metastases at diagnosis. Follow up period was 1-55 months (median 11 months), during which 76 patients (81%) progressed, and 24 (19%) experienced chemotherapy-related toxicity of grade 3 and 4. Median (95%CI) PFS was 8,1 months (7.1-9.1), and median OS was 10 months (8.2-11.7). Genotype frequencies for XRCC1 Arg399Gln were 39.4% for Arg/Arg, 25.5% for Arg/Gln and 3.2% for Gln/Gln genotype. For Rad51 G135C frequencies were 61.7% for G/G, 26.6% for G/C and 1.1% for C/C genotype. Carriers of the XRCC1 Gln allele had a significantly shorter PFS (7.2m vs 9.5m, Breslow p=0.023) and OS (6.4m vs 15.7m, Breslow p=0.04), and were more susceptable to progression during chemotherapy. Although Rad51 genotypes alone had no statistically significant effect on PFS and OS, carriers of both XRCC1 Gln allele and Rad51 C allele had a 4 months shorter OS, the difference was not statistically significant. There were no statistically significant differences in the occurence of high grade chemotherapy-induced toxicity according to the patients' XRCC1 and Rad51 genotypes.
    
    Conclusion:
    These results suggest that in the Serbian population XRCC1 and Rad51 genotyping could be a useful tool for predicting the clinical outcome with platinum-based chemotherapy in advanced EGFR wild-type adenocarcinoma patients.
    
    

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