TGFβ1和ATM基因单核苷酸多态性与放射性肺损伤关系研究
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摘要
目的研究TGFβ1基因上TGFβ1-509C/T、TGFβ1+869T/C,及ATM基因上ATM126713G/A位点单核苷酸多态性与放射性肺损伤的关系。方法招募和随访2010年3月至2012年6月期间接受胸部三维适形放疗的肺癌患者170例,抽取患者静脉血,提取基因组DNA,应用实时荧光定量PCR方法进行基因单核苷酸多态性的基因分型(TGFβ1、ATM)。所有患者放疗后放射性肺损伤评价按NCI CTC 3.0急性放射性肺炎标准评价,SPSS13.0软件包进行数据分析。结果实验分为放射性肺损伤组和未发生放射性肺损伤组,TGFβ1-509C/T、TGFβ1+869T/C和ATM126713G/A的基因型分布频率在两组之间差异无统计学意义(P>0.05),TGFβ1基因上的等位基因T与C发生放射性肺损伤的风险相比差异无统计学意义(P>0.05),ATM基因上等位基因G与A发生放射性肺损伤的风险相比差异无统计学意义(P>0.05)。结论本研究未发现北方汉族人群中TGFβ1和ATM基因单核苷酸多态性与放射性肺损伤发生相关。
Objective To investigate the association of TGFβ1 gene(TGFβ1-509 C/T),(TGFβ1+869 T/C)and ATM gene(ATM126713 G/A)single nucleotide polymorphisms(SNP)with radiation lung injury. Methods 170 lung cancer patients accepting radiation therapy were collected during March 2010 to June 2012. NCI CTC3.0 acute radiation pneumonitis was used for evaluation of lung injury. Taqman real-time PCR was used for analysis of the single neucleotide polymorphisms(SNPs). SPSS 13.0 was used for statistical analysis. Results There was no significant relationship in genotype distribution frequency of TGFβ1 and ATM gene between the radiation lung injury group and non-radiation lung injury group.The Alleles showed no association with radiation lung injury. Conclusion TGFβ1 and ATM gene may not be associated with susceptibility to radiation lung injury in Han Chinese in North China.
Objective To investigate the association of TGFβ1 gene(TGFβ1-509 C/T),(TGFβ1+869 T/C)and ATM gene(ATM126713 G/A)single nucleotide polymorphisms(SNP)with radiation lung injury. Methods 170 lung cancer patients accepting radiation therapy were collected during March 2010 to June 2012. NCI CTC3.0 acute radiation pneumonitis was used for evaluation of lung injury. Taqman real-time PCR was used for analysis of the single neucleotide polymorphisms(SNPs). SPSS 13.0 was used for statistical analysis. Results There was no significant relationship in genotype distribution frequency of TGFβ1 and ATM gene between the radiation lung injury group and non-radiation lung injury group.The Alleles showed no association with radiation lung injury. Conclusion TGFβ1 and ATM gene may not be associated with susceptibility to radiation lung injury in Han Chinese in North China.
引文
[1]Torre LA,Siegel RL,Jemal A.Lung cancer statistics[J].Adv Exp Med Biol,2016,893:1-19.
[2]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66:7-30.
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[4]曹京旭,张旭志.细胞因子与放射性肺损伤[J].国外医学放射医学核医学册,2001,25(4):181-185.
[5]Graham MV,Purdy JA,Emami B,et a1.Clinical dose volume histogram analysis for pneumonitis after 3 D treatment for non.small cell lung cancer(SCLC)[J].Int J Radiat Oncol Biol Phys,1999,45:323-329.
[6]Das SK,Zhou S,Zhang J,et a1.Predicting lung radiotherapy-induced pneumonitis using a model combining parametric Lyman probit with nonparametric decision trees[J].Int J Radiat Oncol Biol Phys,2007,68:1212-1221.
[7]Fernet M,Hall J.Genetic biomarkers of therapeutic radiation sensitivity[J].DNA Repair(Amst),2004,3:1237-1243.
[8]Balkwill F.TNF-in promotion and progression of cancer[J].Cancer Metastasis Rev,2006,25(3):409-416.
[9]Angle S,Falconer A,Edwards SM,et a1.ATM polymorphisms as risk factors for prostate cancer development[J].Br J Cancer,2004,91(4):783-787.
[10]Hall J.The Ataxia-telangiectasia mutated gene and breast cancer:gene expression profiles and sequence variants[J].Cancer Lett,2005,227(2):105-14.
[11]Kruhlak M,Crouch E,Orlov M,et al.The ATM repair pathway inhibits RNA polymerase transcription in response to chromosome breaks[J].Nature,2007,447:730-734.
[12]Seitz H.K,Stickel F.Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress[J].Bio Chem,2006,387,349–360.
[13]Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow?[J].Lancet,2001,357:539-545.
[14]Martey CA,Pollock SJ,?Turner CK,et al.Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts:implications for lung inflammation[J].Am J Physiol Lung Cell Mol Physiol,2004,287(5):L981-91.
[15]Savitsky K,Platzer M,Uziel T,et al.Ataxiatelangieetasia:structural diversity of untranslated sequences suggests complex posttranscriptional regulation of ATM gene expression[J].Nucleic Acids Res,1997,25(9):1678-1684.
[16]Su D,Ma S,Liu P,et al.Genetic polymorphisms and treatment response in advanced non-small cell lung cancer[J].Lung Cancer,2007,56(2):281-288.
[17]Thorstenson Y,Shen P,Tusher V,et a1.Global analysis of ATM polymorphism reveals significant functional constraint[J].Am J Hum Genet,2001,69(2):396-412.
[18]Kim JH,Kim H,Lee KY,et al.Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk[J].Human Molecular Genetics,2006,15(7):1181-1186.
[19]Mc Carron SL,Edwards S,Evans PR,et al.Influence of cytokine gene polylmorphisms on the development of prostate cancer[J].Cancer Res,2002,62(12):3369-3372.
[20]Zienolddiny S,Ryberg D,Maggini V,et al.Polymorphisms of the interleukin-1 beta gene are associated with increased risk of non-small cell lung cancer[J].Int J Cancer,2004,109:353-356.
[21]Asada M,Yasuda H,Ebihara S,et al.Interleukin-1 beta gene polymorphisms associated with risk of lung cancer in Japanese.Lung Cancer,2006,54:261-263.
[22]Campa D,Hung RJ,Mates D,et al.Lack of association between polymorphisms in inflammatory genes and lung cancer risk[J].Cancer Epidemiol Biomarkers Prev,2005,14:538-539.
[23]Vogel U,Christensen J,Wallin H,et al.Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study[J].Mutat Res,2008;639:89-100.
[2]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66:7-30.
[3]丁文,郭岩.放射性肺损伤[J].医学影像杂志,2005,15(9):813-816.
[4]曹京旭,张旭志.细胞因子与放射性肺损伤[J].国外医学放射医学核医学册,2001,25(4):181-185.
[5]Graham MV,Purdy JA,Emami B,et a1.Clinical dose volume histogram analysis for pneumonitis after 3 D treatment for non.small cell lung cancer(SCLC)[J].Int J Radiat Oncol Biol Phys,1999,45:323-329.
[6]Das SK,Zhou S,Zhang J,et a1.Predicting lung radiotherapy-induced pneumonitis using a model combining parametric Lyman probit with nonparametric decision trees[J].Int J Radiat Oncol Biol Phys,2007,68:1212-1221.
[7]Fernet M,Hall J.Genetic biomarkers of therapeutic radiation sensitivity[J].DNA Repair(Amst),2004,3:1237-1243.
[8]Balkwill F.TNF-in promotion and progression of cancer[J].Cancer Metastasis Rev,2006,25(3):409-416.
[9]Angle S,Falconer A,Edwards SM,et a1.ATM polymorphisms as risk factors for prostate cancer development[J].Br J Cancer,2004,91(4):783-787.
[10]Hall J.The Ataxia-telangiectasia mutated gene and breast cancer:gene expression profiles and sequence variants[J].Cancer Lett,2005,227(2):105-14.
[11]Kruhlak M,Crouch E,Orlov M,et al.The ATM repair pathway inhibits RNA polymerase transcription in response to chromosome breaks[J].Nature,2007,447:730-734.
[12]Seitz H.K,Stickel F.Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress[J].Bio Chem,2006,387,349–360.
[13]Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow?[J].Lancet,2001,357:539-545.
[14]Martey CA,Pollock SJ,?Turner CK,et al.Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts:implications for lung inflammation[J].Am J Physiol Lung Cell Mol Physiol,2004,287(5):L981-91.
[15]Savitsky K,Platzer M,Uziel T,et al.Ataxiatelangieetasia:structural diversity of untranslated sequences suggests complex posttranscriptional regulation of ATM gene expression[J].Nucleic Acids Res,1997,25(9):1678-1684.
[16]Su D,Ma S,Liu P,et al.Genetic polymorphisms and treatment response in advanced non-small cell lung cancer[J].Lung Cancer,2007,56(2):281-288.
[17]Thorstenson Y,Shen P,Tusher V,et a1.Global analysis of ATM polymorphism reveals significant functional constraint[J].Am J Hum Genet,2001,69(2):396-412.
[18]Kim JH,Kim H,Lee KY,et al.Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk[J].Human Molecular Genetics,2006,15(7):1181-1186.
[19]Mc Carron SL,Edwards S,Evans PR,et al.Influence of cytokine gene polylmorphisms on the development of prostate cancer[J].Cancer Res,2002,62(12):3369-3372.
[20]Zienolddiny S,Ryberg D,Maggini V,et al.Polymorphisms of the interleukin-1 beta gene are associated with increased risk of non-small cell lung cancer[J].Int J Cancer,2004,109:353-356.
[21]Asada M,Yasuda H,Ebihara S,et al.Interleukin-1 beta gene polymorphisms associated with risk of lung cancer in Japanese.Lung Cancer,2006,54:261-263.
[22]Campa D,Hung RJ,Mates D,et al.Lack of association between polymorphisms in inflammatory genes and lung cancer risk[J].Cancer Epidemiol Biomarkers Prev,2005,14:538-539.
[23]Vogel U,Christensen J,Wallin H,et al.Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study[J].Mutat Res,2008;639:89-100.