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Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small-cell lung cancer

Cited 47 time in Web of Science Cited 48 time in Scopus
Authors
Han, Sae-Won; Jeon, Yoon Kyung; Lee, Kyung-Hun; Keam, Bhumsuk; Hwang, Pil Gyu; Oh, Do-Youn; Lee, Se-Hoon; Kim, Dong-Wan; Im, Seock-Ah; Chung, Doo Hyun; Heo, Dae Seog; Bang, Yung-Jue; Kim, Tae-You
Issue Date
2007-05
Citation
Pharmacogenetics and Genomics, Vol.17 No.5, pp.313-319
Keywords
CA dinucleotide repeat polymorphismepidermal growth factor receptorgefitinibmutationnon-small-cell lung cancer
Abstract
Objective Limited availability of tumoral tissue in non-small-cell lung cancer and presence of epidermal growth factor receptor 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 epidermal growth factor receptor mutation in Korean patients. Patients and methods For 86 advanced non-small-cell lung cancer patients treated with gefitinib, epidermal growth factor receptor 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 (46.5%) and high (sum >= 38) in 46 (53.5%) patients. Although epidermal growth factor receptor mutation was more frequent in high CA repeat patients [17.5% (7/40) in low vs. 28.3% (13/46) in high, P = 0.181, response rate was higher in low CA repeat patients [25.0% (10/40) in low vs. 13.0% (6/46) in high, P = 0.161. In multivariate analysis, low CA repeat was associated with better objective response (odds ratio 71, 95% confidence interval 1.2-40.8; P = 0.029) and time-to-progression (hazard ratio 0.54, 95% confidence interval 0.34-0.88; P = 0.014), independent of the epidermal growth factor receptor mutational status. CA repeat status was not associated with epidermal growth factor receptor expression. Conclusion Low number of CA repeats in intron 1 of epidermal growth factor receptor is associated with gefitinib responsiveness in non-small-cell lung cancer patients independent of epidermal growth factor receptor mutation.
ISSN
1744-6872
URI
http://hdl.handle.net/10371/165558
DOI
https://doi.org/10.1097/FPC.0b013e328011abc0
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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