title: Polymorphisms of BCL2 and BAX Genes Associate with Outcomes in Advanced Non-small cell lung cancer Patients treated with platinum-based Chemotherapy.
abstract: 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.
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Linang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qing
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Chongyi
authors.initials: C
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Shiheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Jinglu
authors.initials: J
authors.lastname: Shan
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D010984:Platinum