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Review
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Korean J Med. 2006;71(1):178-178.
- Intron 1 CA Dinucleotide Repeat Polymorphism and Mutations of EGFR and Gefitinib Responsiveness in Non-Small-Cell Lung Cancer
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Sae-Won Han, Yoon Kyung Jeon, Kyung-Hun Lee, Bhumsuk Keam, Pil Gyu Hwang, Do-Youn Oh, Se-Hoon Lee, Dong-Wan Kim, Seock-Ah Im, Doo Hyun Chung, Dae Seog Heo, Yung-Jue Bang, and Tae-You Kim
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- Intron 1 CA Dinucleotide Repeat Polymorphism and Mutations of EGFR and Gefitinib Responsiveness in Non-Small-Cell Lung Cancer
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, , , , , , , , , , , ,
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1Department of Internal Medicine, Hanyang University College of Medicine, Seoul; 2Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Korea
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- Abstract
- Purpose
: Limited availability of tumoral tissue in non-small-cell lung cancer (NSCLC) and presence of epidermal growth factor
receptor (EGFR) mutation-independent responses call for investigation of other molecular predictive marker of gefitinib
responsiveness. Therefore, CA repeat polymorphism in intron 1 was analyzed for its association with gefitinib responsiveness
together with EGFR mutation in Korean patients. Patients and Methods : For 86 advanced NSCLC patients treated with
gefitinib, EGFR mutation was analyzed by direct sequencing (exons 18-21) from tumor tissue and CA repeat polymorphism was
assessed by fragment length analysis from tumor and/or normal tissue. Results : CA repeat status was identical in 33 patients
with matched tumor and normal tissue. CA repeat was low (sum of both alleles ≤ 37) in 40 patients (46.5%) and high (sum
≥ 38) in 46 (53.5%). Although EGFR mutation was more frequent in high CA repeat patients [17.5% (7/40) in low vs. 28.3%
(13/46) in high, p = 0.18], response rate was higher in low CA repeat patients [25.0% (10/40) in low vs. 13.0% (6/46) in high,
p = 0.16]. In multivariate analysis, low CA repeat was associated with better objective response [odd ratio 7.1, 95% confidence
interval (CI) 1.2 ? 40.8; p = 0.029] and time to progression (hazard ratio 0.54, 95% CI 0.34 - 0.88; p = 0.014) independent of EGFR
mutational status. CA repeat status was not associated with EGFR expression. Conclusion : Low number of CA repeats in
intron 1 of EGFR is associated with gefitinib responsiveness in NSCLC patients independent of EGFR mutation.
Keywords :
