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Original Research |

Association of CASP7 Polymorphisms and Survival of Patients With Non-small Cell Lung Cancer With Platinum-Based Chemotherapy TreatmentCASP7 Polymorphisms and Chemotherapy Outcome

Ji Qian, PhD; Shaohua Gu, PhD; Qihan Wu, PhD; Xueying Zhao, PhD; Wenting Wu, PhD; Zhiqiang Gao, PhD; Wei Zhang, PhD; Xiaoming Tan, PhD; Haijian Wang, PhD; Jiucun Wang, PhD; Weiwei Fan, PhD; Hongyan Chen, PhD; Baohui Han, PhD; Daru Lu, PhD; Qingyi Wei, PhD; Li Jin, PhD
Author and Funding Information

From the State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology (Drs Qian, Gu, Zhao, W. Wu, H. Wang, J. Wang, Fan, Chen, Lu, and Jin), School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University; the School of Life Science (Dr Q. Wu), East China Normal University; the Department of Respiratory Disease (Drs Gao, Zhang, and Han), Shanghai Chest Hospital, and the Department of Respiratory Disease (Dr Tan), Renji Hospital, Shanghai Jiaotong University; the Department of Respiratory Disease (Dr Tan), Changzheng Hospital, Second Military Medical University, Shanghai, China; and the Department of Epidemiology (Drs Qian and Wei), The University of Texas MD Anderson Cancer Center, Houston, TX.

Correspondence to: Daru Lu, PhD, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Science, Fudan University, 220 Handan Rd, Shanghai 200433, China; e-mail: drlu@fudan.edu.cn.


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This work was supported by the National Basic Research Program (973 program) of China [Grant 2011CB503802]; Shanghai Science and Technology Research Program [Grant 06DZ19501]; National Natural Science Foundation of China [Grants NSFC 81172093 and 30890034]; the Shanghai Pujiang Program [Grant 11PJD005]; and the China Ministry of Health [Grant 201002007].


Chest. 2012;142(3):680-689. doi:10.1378/chest.11-2522
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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.

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