Caspase 8polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy

Abstract

Lung cancer is the leading cause of cancer deaths in China, and about 60% of the cases are diagnosed with histological adenocarcinoma. The caspase 8 (CASP8) gene is a critical initiator of the extrinsic apoptosis pathway. To explore the relationship between tagSNPs or haplotypes of CASP8 and the efficacy of platinum-based chemotherapy in advanced lung adenocarcinoma patients of China, we recruited 555 advanced adenocarcinoma patients. We extracted the genomic DNA from patients' peripheral blood samples and sequenced tagSNPs of CASP8. We calculated the individual haplotype of CASP8 frequencies using the PHASE 2.0 program. The association between CASP8 tagSNPs and overall survival (OS) was calculated by univariate and multivariate Cox regression analysis. A univariate logistic regression analysis was done to analyze the CASP8 tagSNPs and the toxicity of platinum-based chemotherapy. The same statistical methods were used for exploring haplotypes of CASP8. Rs3769821 and rs1045494 of CASP8 were independent prognosis factors for overall survival (OS) using multivariate Cox's regression models. For the haplotype of the 7 tagSNPs, haplotype AGGAAAGA was correlated with the efficacy of platinum-based chemotherapy. The polymorphisms of CASP8, rs7608692, and haplotype AGAACAG correlated with neutropenia toxicity. The haplotype GGGGAAA was associated with thrombocytopenia toxicity. We conclude that the polymorphisms of CASP8 contribute to the prognosis of advanced lung adenocarcinoma and influence the quality of life and survival.

WITHDRAWN: Endometrial epithelial cell apoptosis is inhibited via a ciR8073-miR181a-neurotensis pathway during embryo implantation

“…Caspase-8 was crucial for apoptosis progression, when it was degraded or decreased, resulting in immortality of injured cells and induction of various cancers [52]. Furthermore, several studies had suggested that endometrial cell death was increased by the active Caspase-3 during the estrous cycle [53].…”

Individual and combined effect ofTP53, MDM2, MDM4, MTHFR, CCR5,andCASP8gene polymorphisms in lung cancer

“…Caspase-8 (encoded by the CASP8 gene) is crucial in generating cell death signals and eliminating potentially malignant cells. Genetic variation in CASP8 may affect susceptibility to cancer [ 30 , 31 ]. Caspase-8 is a member of the caspase cysteine protease family and plays an important role in cancer development [ 32 ].…”

Expression of Caspase-9 in Early and Locally Advanced Stage Squamous Cell Lung Cancer

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