GNAS1 T393C单核苷酸多态性与肺癌生存及放化疗副反应相关性研究
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摘要
目的分析GNAS1T393C多态性与晚期肺癌患者总生存率的相关性。
方法2010年3月-2012年3月94例病理证实的Ⅲ-Ⅳ期接受放疗或化疗的肺癌患者。提取患者全血基因组DNA,应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点的单核酸多态性基因型。应用SPSS12.0软件Kanlan-Meier生存分析临床因素及基因型与晚期肺癌患者生存的相关性。
结果本组研究94例病例中位年龄为58.6岁,随访至2012年3月,中位生存期为14个月。1年、2年总生存率分别为61%和35%。单因素分析显示并发基础疾病的患者影响生存期下降,P=0.03；GNAS1T393C三种基因型TT,TC和CC间生存率有显著差异,P<0.01；携带等位基因C的患者生存率明显低于等位基因T携带者,P<0.01。
结论GNAS1T393C多态性与肺癌总生存率相关,携带等位基因C的肺癌患者预后差。可能成为晚期肺癌生存的预测因素,需要扩大样本量进行更深入的研究。
目的分析GNAS1T393C多态性与吉西他滨、培美曲塞、紫杉类药物化疗后血液毒性和消化道毒性的相关性。
方法2010年3月-2012年3月在我院接受吉西他滨、培美曲塞、紫杉类药物化疗的肿瘤患者各54例、36例、64例。应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点单核酸多态性的基因型。研究终点为基因型与化疗药物毒性的相关性。临床因素及基因型与化疗药物毒性的相关性采用SPSS12.0软件卡方检验或Fish精确检验。
结果单因素分析显示不吸烟患者接受吉西他滨治疗后容易发生血液毒性,P=0.041; GNAS1T393C多态性与吉西他滨药物毒性无明显相关性。培美曲塞化疗后副反应发生率相对较低,而且多种临床因素均不影响其副反应的发生率。不同GNAS1T393C基因型与紫杉类药物血液毒性显著相关,P=0.023；等位基因T患者接受紫杉类药物化疗后更容易发生骨髓抑制,P=0.017。而且女性接受紫杉类化疗后容易发生骨髓抑制,P=0.008。
结论GNAS1T393C等位基因T携带者与紫杉类化疗药物的血液毒性相关,可能成为其药物毒性的预测因素,需要扩大样本量进行更深入的研究。
目的分析GNAS1T393C多态性与肺癌放疗疗效、血液毒性、放射性食管炎和放射性肺炎的相关性。
方法2010年3月-2012年3月经病理证实的Ⅲ-Ⅳ期接受放疗的肺癌患者67例。应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点单核酸多态性的基因型。应用SPSS12.0软件卡方检验或Fish精确检验分析临床因素及基因型与肺癌放疗疗效、血液毒性、放射性食管炎和放射性肺炎的相关性。
结果本组研究病例中位年龄为61岁。单因素分析显示同时使用化疗可以增加肺癌放疗疗效,P=0.045,但是相应的骨髓抑制发生率增加,P=0.004。肺鳞癌患者更容易发生放射性肺炎,P=0.015；GNAS1T393C等位基因T携带者发生放射性肺炎的比例明显高于等位基因C携带者,P=0.035。
结论GNAS1T393C等位基因T与放射性肺炎相关,可能成为的其预测因素,需要扩大样本量进行更深入的研究。
目的比较GNAS1T393C不同基因型对恶性肿瘤患者生存率的影响,为恶性肿瘤预后评估提供生物分子标记。
方法系统检索MEDLINE、EMBASE.生物医学文献数据库(CBMdisc)、ASCO论文集、EMBASE、COchrane图书管等数据库,收集国内外已发表和未发表的GNAS1T393C多态性与肿瘤预后相关性文献,无语种限制。纳入符合要求的文献,提取不同基因型患者生存资料,应用Revman4.2软件进行meta分析GNAS1T393C不同基因型与恶性肿瘤患者生存率的相关性。
结果纳入符合条件的文献12篇,总例数为2343例,其中TT型526例(22.5%),TC型1128例(48.1%),CC型689例(29.4%)。Meta分析结果显示TT基因型恶性肿瘤患者的五年生存率显著高于CC基因型患者(P=0.0005),合并比值比(OR)及其95%可信区间(95%CI)为1.53(1.21,1.95)；而且TT基因型恶性肿瘤患者的五年生存率也显著高于TC基因型患者(P=0.01),合并比值比(OR)及其95%可信区间(95%CI)为1.38(1.08,1.77)；但是TC与CC基因型恶性肿瘤患者五年生存率间的差异不具有统计学意义(P=0.88),合并比值比(OR)及其95%可信区间(95%CI)为1.02(0.82,1.26)。
结论GNAS1T393C多态性与多种恶性肿瘤生存具有相关性,CC基因型对于绝大多数肿瘤是预后不好的标记,上述结果需要进一步大样本验证研究。
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.
方法2010年3月-2012年3月94例病理证实的Ⅲ-Ⅳ期接受放疗或化疗的肺癌患者。提取患者全血基因组DNA,应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点的单核酸多态性基因型。应用SPSS12.0软件Kanlan-Meier生存分析临床因素及基因型与晚期肺癌患者生存的相关性。
结果本组研究94例病例中位年龄为58.6岁,随访至2012年3月,中位生存期为14个月。1年、2年总生存率分别为61%和35%。单因素分析显示并发基础疾病的患者影响生存期下降,P=0.03；GNAS1T393C三种基因型TT,TC和CC间生存率有显著差异,P<0.01；携带等位基因C的患者生存率明显低于等位基因T携带者,P<0.01。
结论GNAS1T393C多态性与肺癌总生存率相关,携带等位基因C的肺癌患者预后差。可能成为晚期肺癌生存的预测因素,需要扩大样本量进行更深入的研究。
目的分析GNAS1T393C多态性与吉西他滨、培美曲塞、紫杉类药物化疗后血液毒性和消化道毒性的相关性。
方法2010年3月-2012年3月在我院接受吉西他滨、培美曲塞、紫杉类药物化疗的肿瘤患者各54例、36例、64例。应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点单核酸多态性的基因型。研究终点为基因型与化疗药物毒性的相关性。临床因素及基因型与化疗药物毒性的相关性采用SPSS12.0软件卡方检验或Fish精确检验。
结果单因素分析显示不吸烟患者接受吉西他滨治疗后容易发生血液毒性,P=0.041; GNAS1T393C多态性与吉西他滨药物毒性无明显相关性。培美曲塞化疗后副反应发生率相对较低,而且多种临床因素均不影响其副反应的发生率。不同GNAS1T393C基因型与紫杉类药物血液毒性显著相关,P=0.023；等位基因T患者接受紫杉类药物化疗后更容易发生骨髓抑制,P=0.017。而且女性接受紫杉类化疗后容易发生骨髓抑制,P=0.008。
结论GNAS1T393C等位基因T携带者与紫杉类化疗药物的血液毒性相关,可能成为其药物毒性的预测因素,需要扩大样本量进行更深入的研究。
目的分析GNAS1T393C多态性与肺癌放疗疗效、血液毒性、放射性食管炎和放射性肺炎的相关性。
方法2010年3月-2012年3月经病理证实的Ⅲ-Ⅳ期接受放疗的肺癌患者67例。应用PCR扩增目的基因片段,sanger双脱氧测序方法分析GNAS1T393C位点单核酸多态性的基因型。应用SPSS12.0软件卡方检验或Fish精确检验分析临床因素及基因型与肺癌放疗疗效、血液毒性、放射性食管炎和放射性肺炎的相关性。
结果本组研究病例中位年龄为61岁。单因素分析显示同时使用化疗可以增加肺癌放疗疗效,P=0.045,但是相应的骨髓抑制发生率增加,P=0.004。肺鳞癌患者更容易发生放射性肺炎,P=0.015；GNAS1T393C等位基因T携带者发生放射性肺炎的比例明显高于等位基因C携带者,P=0.035。
结论GNAS1T393C等位基因T与放射性肺炎相关,可能成为的其预测因素,需要扩大样本量进行更深入的研究。
目的比较GNAS1T393C不同基因型对恶性肿瘤患者生存率的影响,为恶性肿瘤预后评估提供生物分子标记。
方法系统检索MEDLINE、EMBASE.生物医学文献数据库(CBMdisc)、ASCO论文集、EMBASE、COchrane图书管等数据库,收集国内外已发表和未发表的GNAS1T393C多态性与肿瘤预后相关性文献,无语种限制。纳入符合要求的文献,提取不同基因型患者生存资料,应用Revman4.2软件进行meta分析GNAS1T393C不同基因型与恶性肿瘤患者生存率的相关性。
结果纳入符合条件的文献12篇,总例数为2343例,其中TT型526例(22.5%),TC型1128例(48.1%),CC型689例(29.4%)。Meta分析结果显示TT基因型恶性肿瘤患者的五年生存率显著高于CC基因型患者(P=0.0005),合并比值比(OR)及其95%可信区间(95%CI)为1.53(1.21,1.95)；而且TT基因型恶性肿瘤患者的五年生存率也显著高于TC基因型患者(P=0.01),合并比值比(OR)及其95%可信区间(95%CI)为1.38(1.08,1.77)；但是TC与CC基因型恶性肿瘤患者五年生存率间的差异不具有统计学意义(P=0.88),合并比值比(OR)及其95%可信区间(95%CI)为1.02(0.82,1.26)。
结论GNAS1T393C多态性与多种恶性肿瘤生存具有相关性,CC基因型对于绝大多数肿瘤是预后不好的标记,上述结果需要进一步大样本验证研究。
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.
引文
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