目的：通过检测BCL-2基因多态性，探讨其与复治晚期非小细胞肺癌表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗疗效的关系。方法116例复治晚期非小细胞肺癌患者，既往均接受过化疗，失败后接受吉非替尼或厄洛替尼靶向治疗。采用多聚酶链反应方法检测患者外周血白细胞中BCL-2基因多态性。结果116例患者总有效率为25.9%，BCL-2各基因型间患者间的有效率无明显差异。相比BCL-2其它基因型，AA型疾病控制率更低（40%vs 75.2%，P=0.005）。单因素分析中位PFS， AA型中位无进展时间短于其它基因型（2.6个月vs 6.0个月，P=0.025），而女性长于男性（10.2个月vs 4.6个月，P=0.04）；不吸烟者长于有吸烟史者（11.9个月vs2.5个月，P=0.000）；病理类型为腺癌长于其他类型（11.9个月vs 4.1个月，P=0.000），均达到统计学差异。多因素分析结果显示，包括性别、吸烟史、ECOG评分和病理类型，BCL-2基因多态性为PFS的独立预后因素（P=0.049）。结论复治晚期EGFR突变状态未明的非小细胞肺癌BCL-2（-938C＞A）基因型为AA者是提示近期疗效较差的指标。%Objective To investigate the association between BCL- 2 gene polymorphism and therapeutic efficacy of tyro-sine kinase inhibitor(TKI) in pretreated patients with advanced non- smal celllung cancer(NCSLC). Methods A total of 116 pa-tients with advanced NSCLC were recruited from Zhejiang Cancer Hospital, al of whom were treated with gefitinib or erlotinib after failure to chemotherapy. BCL- 2 gene polymorphism of peripheral blood lymphocytes was detected with polymerase chain reac-tion (PCR). Statistical analysis was performed by SPSS version 13.0. Results The overal response rate was 28.9%. No significant association was found between BCL- 2(- 938C>A) polymorphism and the objective response rate. The disease control rate of pa-tients with BCL- 2 AA genotype was lower than that of patients with genotype CC or CA (40%vs 75.2%, P=0.005). Univariate anal-ysis identified gender, smoking history, histology and BCL- 2 (- 938C>A) polymorphism as predictive markers of progress free survival(PFS) (P=0.04, P=0.000, P=0.000 and P=0.05). Multivariate analysis demonstrated that BCL- 2 (- 938C>A) polymorphism was correlated independently with PFS (P=0.049). Conclusion Our data suggest that BCL- 2 (- 938C>A) AA genotype may be a predictive marker for poor DCR and PFS in advanced NSCLC patients treated with tyrosine kinase inhibitor.
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