TY - JOUR
T1 - Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer
AU - Qian, Ji
AU - Qu, Hui Qi
AU - Yang, Lixin
AU - Yin, Ming
AU - Wang, Qiming
AU - Gu, Shaohua
AU - Wu, Qihan
AU - Zhao, Xueying
AU - Wu, Wenting
AU - Wu, Junjie
AU - Tan, Xiaoming
AU - Chen, Wenqing
AU - Wang, Haijian
AU - Wang, Jiucun
AU - Fan, Weiwei
AU - Chen, Hongyan
AU - Han, Baohui
AU - Lu, Daru
AU - Wei, Qingyi
AU - Jin, Li
PY - 2012
Y1 - 2012
N2 - Caspase-8 and caspase-10 play crucial roles in both cancer development and chemotherapy efficacy. In this study, we aimed to comprehensively assess single nucleotide polymorphisms (SNPs) of the caspase-8 (CASP8) and caspase-10 (CASP10) genes in relation to toxicity outcomes with first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 13 tag SNPs of CASP8 and CASP10 in 663 patients with advanced NSCLC treated with platinum-based chemotherapy regimens. Associations between SNPs and chemotherapy toxicity outcomes were identified in a discovery set of 279 patients and then validated in an independent set of 384 patients. In both the discovery and validation sets, variant homozygotes of CASP8 rs12990906 and heterozygotes of CASP8 rs3769827 and CASP10 rs11674246 and rs3731714 had a significantly lower risk for severe toxicity overall. However, only the association with the rs12990906 variant was replicated in the validation set for hematological toxicity risk. In a stratified analysis, we found that some other SNPs, including rs3769821, rs3769825, rs7608692, and rs12613347, were significantly associated with severe toxicity risk in some subgroups, such as in nonsmoking patients, patients with adenocarcinoma, and patients treated with cisplatin combinations. Consistent results were also found in haplotype analyses. Our results provide novel evidence that polymorphisms in CASP8 and CASP10 may modulate toxicity outcomes in patients with advanced NSCLC treated with platinum-based chemotherapy. If validated, the findings will facilitate the genotype-based selection of platinum-based chemotherapy regimens.
AB - Caspase-8 and caspase-10 play crucial roles in both cancer development and chemotherapy efficacy. In this study, we aimed to comprehensively assess single nucleotide polymorphisms (SNPs) of the caspase-8 (CASP8) and caspase-10 (CASP10) genes in relation to toxicity outcomes with first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 13 tag SNPs of CASP8 and CASP10 in 663 patients with advanced NSCLC treated with platinum-based chemotherapy regimens. Associations between SNPs and chemotherapy toxicity outcomes were identified in a discovery set of 279 patients and then validated in an independent set of 384 patients. In both the discovery and validation sets, variant homozygotes of CASP8 rs12990906 and heterozygotes of CASP8 rs3769827 and CASP10 rs11674246 and rs3731714 had a significantly lower risk for severe toxicity overall. However, only the association with the rs12990906 variant was replicated in the validation set for hematological toxicity risk. In a stratified analysis, we found that some other SNPs, including rs3769821, rs3769825, rs7608692, and rs12613347, were significantly associated with severe toxicity risk in some subgroups, such as in nonsmoking patients, patients with adenocarcinoma, and patients treated with cisplatin combinations. Consistent results were also found in haplotype analyses. Our results provide novel evidence that polymorphisms in CASP8 and CASP10 may modulate toxicity outcomes in patients with advanced NSCLC treated with platinum-based chemotherapy. If validated, the findings will facilitate the genotype-based selection of platinum-based chemotherapy regimens.
KW - Association
KW - CASP10
KW - CASP8
KW - Non-small cell lung cancer
KW - Platinum-based chemotherapy
KW - Polymorphisms
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84871558982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871558982&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2011-0419
DO - 10.1634/theoncologist.2011-0419
M3 - Article
C2 - 22843554
AN - SCOPUS:84871558982
SN - 1083-7159
VL - 17
SP - 1551
EP - 1561
JO - Oncologist
JF - Oncologist
IS - 12
ER -