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S.Y. Lee



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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-001 - A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population (ID 3348)

      09:30 - 16:30  |  Author(s): S.Y. Lee

      • Abstract

      Background
      MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.

      Methods
      The rs2910164C>G genotypes were determined in 1,094 patients with lung cancer and 1,100 healthy controls who were frequency matched for age and gender.

      Results
      The rs2910164 CG or GG genotype was associated with a significantly decreased risk for lung cancer compared to that of the CC genotype (adjusted odds ratio = 0.80, 95% confidence interval = 0.66-0.96, P = 0.02). When subjects were stratified according to smoking exposure (never, light and heavy smokers), the effect of the rs2910164C>G genotype on lung cancer risk was significant only in never smokers (adjusted odds ratio = 0.66, 95% confidence interval = 0.45-0.96, P = 0.03, under a dominant model for the C allele) and decreased as smoking exposure level increased (P~trend~ < 0.001).

      Conclusion
      These findings suggest that the rs2910164C>G in pre-miR-146a may contribute to genetic susceptibility to lung cancer, and that miR-146a might be involved in lung cancer development.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-027 - Polymorphisms in DNA repair and apoptosis-related genes and clinical outcomes of patients with non-small cell lung cancer treated with first-line paclitaxel-cisplatin chemotherapy (ID 2196)

      09:30 - 16:30  |  Author(s): S.Y. Lee

      • Abstract

      Background
      This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNPs) in genes in DNA repair and apoptosis pathways and determine the relationship between polymorphisms and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with first-line paclitaxel-cisplatin chemotherapy.

      Methods
      Three hundred eighty two patients with NSCLC were enrolled. Seventy-four SNPs in 48 genes (42 SNPs in 27 DNA repair pathway genes and 32 SNPs in 21 apoptotic pathway genes) were genotyped and their associations with chemotherapy response and overall survival (OS) were analyzed.

      Results
      Among SNPs in DNA repair genes, BRCA1 rs799917 was significantly associated with both chemotherapy response and OS. XRCC1 rs25487 exhibited a significant association with chemotherapy response and ERCC2 rs1052555 with OS. Four SNPs in apoptotic genes (TNFRSF1B rs1061624, BCL2 rs2279115, BIRC5 rs9904341, and CASP8 rs3769818) were significantly associated with OS, but not with response to chemotherapy. When the six SNPs which were associated with OS in individual analysis were combined, OS decreased as the number of bad genotypes increased (P~trend~ = 2ⅹ10[-6]). Patients with 3, and 4-6 bad genotypes had significantly worse OS compared with those carrying 0-2 bad genotypes (adjusted hazard ratio [aHR] = 1.54, 95% CI = 1.14-2.08, P = 0.005; aHR = 2.10, 95% CI = 1.55-2.85, P = 2ⅹ10[-6], respectively).

      Conclusion
      In conclusion, these findings suggest that the SNPs identified could be used as biomarkers predicting chemotherapy response and survival of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.

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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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      P2.06-044 - The influence of TP53 mutation on the prognosis of patients with early<br /> stage non-small cell lung cancer may depend on the intratumor<br /> heterogeneity of the mutation (ID 3083)

      09:30 - 16:30  |  Author(s): S.Y. Lee

      • Abstract

      Background
      A large number of studies have evaluated the impact of TP53 mutation on the prognosis of patients with non-small cell lung cancer (NSCLC); however, the results of these studies are still controversial. Recently, considerable intratumor heterogeneity for genetic alterations has been demonstrated in various human cancers, including lung cancer.

      Methods
      In the present study, we evaluated TP53 mutations in NSCLCs by direct sequencing and observed remarkable variation in the values of the relative intensity (RI, the height of the peak of mutated allele/the height of the peak of non-mutated allele) of TP53 mutation. We also examined whether the RI values were associated with intratumor heterogeneity of TP53 mutation. In addition, we evaluated the relationship between TP53 mutation and survival outcome.

      Results
      The patients with TP53 mutation did not have significantly worse survival compared to those without the mutation. However, when tumors with TP53 mutation were categorized into two groups, those with a low and those with a high RI, the latter group had significantly worse survival compared to those with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21-5.48, P = 0.01), whereas the former group did not.

      Conclusion
      These results suggest that intratumor genetic heterogeneity may be an important factor in determining the role of TP53 mutation on the prognosis of NSCLC patients.