title: Association of CASP7 polymorphisms and survival of patients with non-small cell lung cancer with platinum-based chemotherapy treatment.
abstract: BACKGROUND
  CASP7 plays a crucial role in cancer development and chemotherapy efficacy. We, therefore, explored whether single nucleotide polymorphisms (SNPs) of the CASP7 gene can modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.
  
  
  METHODS
  We systematically genotyped 17 SNPs of CASP7 first in a discovery set of 279 patients with advanced NSCLC treated with platinum-based chemotherapy and then replicated the results in an independent set of 384 patients, in whom we evaluated associations with overall survival (OS) and progress-free survival (PFS) by Kaplan-Meier analysis and Cox hazards regression analysis.
  
  
  RESULTS
  In both discovery and validation sets as well as in the pooled analysis, heterozygotes of CASP7 rs2227310 and rs4353229 as well as rs12415607 variant allele were strongly associated with a better OS of NSCLC (in the pooled sample: adjusted hazard ratio [HR], 0.73; 95% CI = 0.59-0.90; P = .003; HR, 0.72; 95% CI = 0.59-0.89; P = .002; and HR, 0.76; 95% CI = 0.62-0.94; P = .009; respectively). In stratified analyses of the pooled data set, treated with paclitaxel, individuals carrying variant allele of rs2227310, rs4353229, and rs12415607 had significantly improved OS (HR, 0.60; 95% CI = 0.41-0.87; P = .008; HR, 0.58; 95% CI = 0.39-0.84; P = .004; and HR, 0.61; 95% CI = 0.42-0.89; P = .010; respectively).
  
  
  CONCLUSIONS
  This study provides evidence that genetic variations of CASP7 may modulate OS and PFS of patients with advanced NSCLC treated with platinum-based chemotherapy.
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gu
authors.affiliation: School of Life Science, East China Normal University, Shanghai, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Disease, Renji Hospital, Shanghai Jiaotong University, Shanghai, China; Department of Respiratory Disease, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China. Electronic address: drlu@fudan.edu.cn.
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D053179:Caspase 7 / Q000235:genetics*; D004358:Drug Therapy; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010984:Platinum / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum; C505520:CASP7 protein, human; D053179:Caspase 7