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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

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=0.18], 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 (odds ratio 7.1, 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.