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Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer.

Publication ,  Journal Article
Qian, J; Qu, H-Q; Yang, L; Yin, M; Wang, Q; Gu, S; Wu, Q; Zhao, X; Wu, W; Wu, J; Tan, X; Chen, W; Wang, H; Wang, J; Fan, W; Chen, H ...
Published in: Oncologist
2012

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.

Duke Scholars

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Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

2012

Volume

17

Issue

12

Start / End Page

1551 / 1561

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Platinum
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Logistic Models
  • Humans
  • Haplotypes
  • Gene Frequency
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Qian, J., Qu, H.-Q., Yang, L., Yin, M., Wang, Q., Gu, S., … Jin, L. (2012). Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Oncologist, 17(12), 1551–1561. https://doi.org/10.1634/theoncologist.2011-0419
Qian, Ji, Hui-Qi Qu, Lixin Yang, Ming Yin, Qiming Wang, Shaohua Gu, Qihan Wu, et al. “Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer.Oncologist 17, no. 12 (2012): 1551–61. https://doi.org/10.1634/theoncologist.2011-0419.
Qian, Ji, et al. “Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer.Oncologist, vol. 17, no. 12, 2012, pp. 1551–61. Pubmed, doi:10.1634/theoncologist.2011-0419.
Qian J, Qu H-Q, Yang L, Yin M, Wang Q, Gu S, Wu Q, Zhao X, Wu W, Wu J, Tan X, Chen W, Wang H, Wang J, Fan W, Chen H, Han B, Lu D, Wei Q, Jin L. Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer. Oncologist. 2012;17(12):1551–1561.

Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

2012

Volume

17

Issue

12

Start / End Page

1551 / 1561

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Platinum
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Logistic Models
  • Humans
  • Haplotypes
  • Gene Frequency