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Association Of The GNAS1T393C Polymorphism With Survival In Advanced Lung Cancer And Side Effects In Chemotherapy And Radiotherapy

Posted on:2013-11-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Y GongFull Text:PDF
GTID:1224330377456388Subject:Clinical Medicine
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Objective To examine the possible relationship between SNP of GNAS1T393C and outcomes of advanced lung cancer.Methods and Materials Between March2010and March2012,genomic DNA was extracted from whole blood of94advanced lung cancer patients confirmed by pathology in this study. Allelic discrimination of GNAS1was performed by quantitative real-time polymerase chain reaction. Genetyping was correlated with survival of advanced lung cancer. The Kaplan-Meier method and log-rank test were used to assess the prognostic significance of the clinical factors and genotypes for survival. Cox forward-stepwise regression model was chosen to assess genetic risk factors in multivariate analyses.Results Median age was58.6years(rang,31to80years), By the last follow-up time in March,2012, overall median survival was14months; the1-,2-year ovrall survival were61%and35%. At univriate analysis, the overall survival received benefit from TT genetype of GNAS1T393C(P=0.001).Conclusions Genetic polymorphism in the GNAS1T393C was related to outcomes of advaced lung cancer, which may be a prognostic factor. The results needed large sample research to identify. Objective To examine the possible relationship between SNP of GNAS1T393C and side effects of gemcitabine, pemetrexed and paclitaxel.Methods and Materials Between March2010and March2012,genomic DNA was extracted from whole blood of54,36,64patients underwent chemotherapy of gemcitabine, pemetrexed and paclitaxel. respectively. Allelic discrimination of GNAS1was performed by quantitative real-time polymerase chain reaction. Genetyping was correlated with side effects of gemcitabine, pemetrexed and paclitaxel. The endpoint was grade>3chemothrapy-induced hematological and digestive toxicity. The Chi-square criterion method and log-rank test were used to assess the significance of the clinical factors and genotypes for side effects of chemothrapy.Results Median age was60years(rang26to75years). At univriate analysis, non-smokers had myelosuppression after receiving gemcitabine (P=0.041); The female had hematotoxicity after receiving paclitaxel(P=0.008); Allele T carrier in GNAS1T393C gene had hematotosicity after recerving paclitaxel (P=0.017).Conclusions Genetic polymorphism in the GNAS1T393C was related to hematotosicity of paclitaxel. The results needed large sample research to identify. Objective To examine the possible relationship between SNP of GNAS1T393C and curative effect of radiotherapy and radiation-induced hematological toxicity, esophagitis and pneumonia.Methods and Materials Between March2010and March2012,genomic DNA was extracted from whole blood of65advaced lung cancer patients underwent radiotherapy. Allelic discrimination of GNAS1was performed by quantitative real-time polymerase chain reaction. Genetyping was correlated with curative effect of radiotherapy and radiation-induced hematological toxicity, esophagitis and pneumonia. The endpoint was grade>3hematological toxicity and grade>2radiation-induced esophagitis and pneumonia. The Chi-square criterion method and log-rank test were used to assess the significance of the clinical factors and genotypes for curative effect of radiotherapy and radiation-induced hematological toxicity, esophagitis and pneumonia. Results Median age was61years(rang35to80years). At univriate analysis, chemotherapy could augment the efficacy of radiotherapy in lung cancer (P=0.045); But the hematotoxicity increased(P=0.004); Squanae type and allele T carrier in GNAS1T393C gene occure radio-induced lung injury more(P-0.015,P=0.035).Conclusions Genetic polymorphism in the GNAS1T393C was related to radio-induced lung injury, which may be a prognostic factor. The results needed large sample research to identify. Objective To evaluate the relationship between SNP of GNAS1T393C and outcomes of cancer.Methods and Materials We searched The Cochrane Library, MEDL1NE, EMBASE, CBM. Using a defined search strategy, randomized controlled trails and controlled clinical trials of comparing were identified. Meta-analysis was done using the Cochrane collaboration’s Revman4.2.Results Twelve controlled clinical articles were included. Five hundred and twelvety-six (22.5%) patients displayed a TT genotype,1128(48.1%) for a CT genotype and689(29.4%) for a CC genotype.The meta-analysis showed that:the five-years survival rate of TT genotype group was significantly higher than CC genotype group [OR=1.53,95%CI (1.21,1.95), P=0.005], which was also higher than TT genotype group[OR=1.38,95%C1(1.08,1.77), P=0.01]. But the difference of survival rate between CT genotype group and CC genotype group was not significant[OR=1.02,95%C1(0.82,1.26), P=0.88].Conclusions Genetic polymorphism in the GNAS1T393C was related to outcomes of advaced lung cancer. CC genotype may be a prognostic factor. The results needed large sample research to identify.
Keywords/Search Tags:GNAS1T393C, SNP, lung cancer, survivalGNAS1T393C, chemotherapy, side effectsGNAS1T393C, radiotherapy, cancer, survival, meta-analysis
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