The Research Of Caspase8and Caspase3Gene Polymorphisms And Sensitivity Of Platinum-based Chemotherapy In Advanced Non-small Cell Lung Cancer

ObjectiveTo investigate the relationship between gene polymorphisms of caspase8and caspase3and sensitivity of platinum-based chemotherapy in advancednon-small cell lung cancer（NSCLC）, and to provide a theoretical basis forindividualized treatment of lung cancer.MethodsPeripheral blood of143advanced non-small cell lung cancer patients werecollected.Genomic DNA were extracted by DNA extraction kits.Genotypes ofpatients were classified by using PCR-RELP.The efficacy and long-term effectswere recorded. Statistical analysis was performed by using SPSS16.0.Results1. Gene polymorphism exast in caspase8rs3769818, rs3834129andcaspase3rs4647693. Gene frequency are as follows: rs3769818C/C70.6%(101/143),C/T24.5%(35/143),T/T4.9%(7/143)； rs3834129Del/Del10.5%(15/143),Del/Ins42.0%(60/143),Ins/Ins47.5%(68/143)；rs4647693A/A40.6%(58/143),A/G51.0%(73/143),G/G8.4(12/143).2. Gene polymorphism of caspase8rs3834129and caspase3rs4647693were associated with short-term effect.The efficacy of patients with6bp Deltreated by cisplatin was higher than those with Ins/Ins（45.33%vs25%， P=0.011）. The efficacy of patients with A/A genotype was also higher thanthose with A/G and G/G genotype（39.66%vs32.94%，P=0.025）. There is nosignificant difference between SNPs of caspase8rs3769818in short-termefficacy （P>0.05）. There are no relationship between sex, age, KPS,pathological type，stage and short-term effect of cisplatin chemotherapy.3. For caspase8rs3834129, the risk of disease progression of patientstreated by platinum who carry Ins/Ins genotype is2.49times of ones with Delallele gene(95%CI:1.22~5.07, P=0.011); for caspase3rs4647693, the risk ofdisease progression of patients treated by platinum who carry G allele genotypeis2.21times of ones with A/A genetype(95%CI:1.10~4.46, P=0.025).4. Joint analysis of caspase8rs3834129and caspase3rs4647693showsthat these two joint gene polymorphisms are associated with the recent curativeeffect of advanced NSCLC, the curative effect of platinum based chemotherapyof patients with Del/Del+Del/Ins and A/A is better than the other three kinds，the latter risk of disease progression were2.72,3.17,6.00, P<0.05.5.SNPs of caspase8rs3769818and caspase3rs4647693show significantdifference in PFS，mid-PFS in patients with C/C of caspase8rs3769818islonger than those with C/T and T/T genotype（164d vs122d，P=0.016）. mid-PFSin patients with A/A of caspase3rs4647693is longer than those with A/G andG/G genotype（173d vs143d，P=0.013）. The above two SNPs and the stage ofdisease impact PFS together.While SNP of rs3834129shows no significantdifference in PFS.6. Joint analysis of caspase8rs3769818rs4647693caspase3showedthese two joint gene polymorphisms are associated with the effect of advancedNSCLC. The effect of platinum based chemotherapy of patients with C/C andA/A is better than ones with T and G allele together（P=0.001），But there is nosignificant difference between ones carrying T or G allele individually. Conclusion1.Caspase8rs3769818, rs3834129and caspase3rs4647693genepolymorphism are one of factors of sensitivity of patients with advanced NSCLCtreated by platinum-based chemotherapy; Patients treated by platinum withNSCLC with T allele of caspase8rs3769818, Ins/Ins of caspase8rs3834129and G allele of caspase3rs4647693may be factors of low sensitivity;2.Caspase8rs3769818, rs3834129and caspase3rs4647693genepolymorphism may be predictors of efficacy of advanced NSCLC treated byplatinum.