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EGFR Polymorphism as a Predictor of Clinical Outcome in Advanced Lung Cancer Patients Treated with EGFR-TKI

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Purpose: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Materials and Methods: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. Results:SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. Conclusion: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.

Abstract

Purpose: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Materials and Methods: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. Results:SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. Conclusion: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.

참고문헌 (24)

  1. Shepherd FA, "Erlotinib in previously treated non-small-cell lung cancer", N Engl J Med, 353, pp.123~132 (2005)
  2. "J Clin Oncol", 2003, 2237~2246
  3. Pérez-Soler R, "Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer", J Clin Oncol, 22, pp.3238~3247 (2004)
  4. Miller VA, "Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer", J Clin Oncol, 22, pp.1103~1109 (2004)
  5. West HL, "Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest Oncology Group Study S0126", J Clin Oncol, 24, pp.1807~1813 (2006)
  6. Pao W, "EGF receptor gene mutations are common in lung cancers from"never smokers"and are associated with sensitivity of tumors to gefitinib and erlotinib", Proc Natl Acad Sci U S A, 101, pp.13306~13311 (2004)
  7. Lynch TJ, "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib", N Engl J Med, 350, pp.2129~2139 (2004)
  8. Tokumo M, "The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers", Clin Cancer Res, 11, pp.1167~1173 (2005)
  9. Yang CH, "Specific EGFR mutations predict treatment outcome of stage IIIB", IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy, 2008, pp.26, 2745~2753
  10. Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma", N Engl J Med, 361, pp.947~957 (2009)
  11. Fukuoka M, "Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin", paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS), 2011, pp.29, 2866~2874
  12. Hlinkova K, "Rapid and efficient detection of EGFR mutations in problematic cytologic specimens by high-resolution melting analysis", Mol Diagn Ther, 15, pp.21~29 (2011)
  13. Tsao MS, "Erlotinib in lung cancer - molecular and clinical predictors of outcome", N Engl J Med, 353, pp.133~144 (2005)
  14. Cappuzzo F, "Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer", J Natl Cancer Inst, 97, pp.643~655 (2005)
  15. Nomura M, "Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell lung cancers", PLoS Med, 4, pp.125~ (2007)
  16. Nie Q, "CYP1A1*2A polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI and its combined effects with EGFR intron 1 (CA)n polymorphism", Eur J Cancer, 47, pp.1962~1970 (2011)
  17. Liu W, "A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor gene promoter", Cancer Res, 65, pp.46~53 (2005)
  18. Travis WD, "Histological typing of lung and pleural tumours. 3rd ed" (1999), Springer-Verlag
  19. Therasse P, "New Guidelines to Evaluate the Response to Treatment in Solid Tumors", pp.205~216 (2000), Oxford University Press
  20. Shigematsu H, "Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers", J Natl Cancer Inst, 97, pp.339~346 (2005)
  21. Amador ML, "An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors", Cancer Res, 64, pp.9139~9143 (2004)
  22. Liu W, "Interethnic difference in the allelic distribution of human epidermal growth factor receptor intron 1 polymorphism", Clin Cancer Res, 9, pp.1009~1012 (2003)
  23. 한세원, "Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small-cell lung cancer", PHARMACOGENETICS AND GENOMICS, 17, pp.313~319, LIPPINCOTT WILLIAMS & WILKINS
  24. Puyo S, "Impact of EGFR gene polymorphisms on anticancer drug cytotoxicity in vitro", Mol Diagn Ther, 12, pp.225~234 (2008)

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