TY - JOUR
T1 - Association of CASP7 polymorphisms and survival of patients with non-small cell lung cancer with platinum-based chemotherapy treatment
AU - Qian, Ji
AU - Gu, Shaohua
AU - Wu, Qihan
AU - Zhao, Xueying
AU - Wu, Wenting
AU - Gao, Zhiqiang
AU - Zhang, Wei
AU - Tan, Xiaoming
AU - Wang, Haijian
AU - Wang, Jiucun
AU - Fan, Weiwei
AU - Chen, Hongyan
AU - Han, Baohui
AU - Lu, Daru
AU - Wei, Qingyi
AU - Jin, Li
N1 - Funding Information:
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 ].
PY - 2012/9
Y1 - 2012/9
N2 - 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 5= 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.
AB - 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 5= 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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U2 - 10.1378/chest.11-2522
DO - 10.1378/chest.11-2522
M3 - Article
C2 - 22441531
AN - SCOPUS:84865854073
SN - 0012-3692
VL - 142
SP - 680
EP - 689
JO - Chest
JF - Chest
IS - 3
ER -