Peng Yu, Wang Linang, Qing Yi, Li Chongyi, Ren Tao, Li Qing, Li Mengxia, Zhang Shiheng, Shan Jinglu, Wang Ge, Yang Zhenzhou, Wang Dong
Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Sci Rep. 2015 Dec 10;5:17766. doi: 10.1038/srep17766.
Single-nucleotide polymorphisms (SNP) of the gene belonging to the BCL2 family are thought to play a role in chemotherapy resistance. This study investigated the association of BCL2-938C>A(rs2279115) and BAX-248G>A(rs4645878) promoter region SNPs and the clinical responses and outcomes of 235 non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. The data suggested that BAX-248GA and GA+AA genotype was associated with poor response [odds ratio (OR) 1.943, p = 0.039; OR 1.867, p = 0.038, respectively] to chemotherapy, and BCL2-938CA, CA+AA and BAX-248GA, AA and GA+AA were associated with poor progression-free survival (PFS) [hazard ratio (HR) 1.514, p = 0.004; HR 1.456, p = 0.009; HR 1.449, p = 0.013; HR 2.006, p = 0.010; HR 1.506, p = 0.003, respectively] and BCL2-938CA, AA and CA+AA and BAX-248GA, AA and GA+AA were associated with poor overall survival (OS) (HR 2.006, p < 0.001; HR 2.322, p < 0.001; HR 2.096, p < 0.001; HR 1.632, p = 0.001; HR 2.014, p = 0.010; HR 1.506, p < 0.001, respectively). Furthermore, combination of these two polymorphisms showed patients with 2-4 variant alleles of these two genes associated with poor PFS and OS (HR 1.637, p = 0.001; HR 2.365, p < 0.001). The data from the current study provide evidence that BCL2-938C>A and BAX-248G>A polymorphisms may be useful in predicting clinical outcomes of patients with advanced inoperable NSCLC to platinum-based chemotherapy.
属于BCL2家族的基因的单核苷酸多态性（SNP）被认为在化疗耐药中起作用。本研究调查了BCL2 - 938C>A（rs2279115）和BAX - 248G>A（rs4645878）启动子区域单核苷酸多态性与235例接受铂类化疗的非小细胞肺癌（NSCLC）患者的临床反应和预后的相关性。数据表明，BAX - 248GA和GA + AA基因型与化疗反应不佳相关[优势比（OR）分别为1.943，p = 0.039；OR 1.867，p = 0.038]，BCL2 - 938CA、CA + AA以及BAX - 248GA、AA和GA + AA与无进展生存期（PFS）不佳相关[风险比（HR）分别为1.514，p = 0.004；HR 1.456，p = 0.009；HR 1.449，p = 0.013；HR 2.006，p = 0.010；HR 1.506，p = 0.003]，BCL2 - 938CA、AA和CA + AA以及BAX - 248GA、AA和GA + AA与总生存期（OS）不佳相关（HR分别为2.006，p < 0.001；HR 2.322，p < 0.001；HR 2.096，p < 0.001；HR 1.632，p = 0.001；HR 2.014，p = 0.010；HR 1.506，p < 0.001）。此外，这两种多态性的组合显示，这两个基因有2 - 4个变异等位基因的患者与PFS和OS不佳相关（HR 1.637，p = 0.001；HR 2.365，p < 0.001）。本研究数据提供了证据表明，BCL2 - 938C>A和BAX - 248G>A多态性可能有助于预测晚期无法手术切除的NSCLC患者接受铂类化疗的临床结局。
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