title: Caspase 8 polymorphisms 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.
authors.affiliation: a Department of Thoracic Surgery , Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: b Department of Respirology and Critical Care Medicines , Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: c Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Ding
authors.affiliation: d Department of Thoracic Surgery , Shanghai Chest Hospital, Shanghai Jiaotong Universtiy , Shanghai , P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: e Department of Oncology , Affiliated Dongyang Hospital of Wenzhou Medical University , Dongyang , Zhejiang , P.R. China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: a Department of Thoracic Surgery , Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Fei
authors.affiliation: c Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053181:Caspase 8 / Q000235:genetics*; D002681:China / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage* / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D011788:Quality of Life
chemical_list: D010984:Platinum; D053181:Caspase 8
keywords: Caspase 8; chemotherapy; lung cancer; platinum; single nucleotide polymorphism