ATM基因rs175048位点单核苷酸多态性与湖南衡阳地区汉族人群肺癌易感性的相关性
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摘要
目的:探讨肺癌易感性与毛细血管扩张性共济失调突变基因(ATM) rs175048位点单核苷酸多态性(SNP)之间的相关性。方法:选取2015年10月至2016年8月在南华大学附属第一医院及衡阳市中医院就诊的汉族肺癌患者血液样本225例(病例组),同时收集在院体检的健康人血液样本128例作为对照组。采用高保真聚合酶介导的单核苷酸多态性敏感性分子开关结合PCR技术检测肺癌患者与健康体检者ATM基因rs175048A/T多态位点的多态性,统计其基因型及等位基因频率,比较其在病例组与对照组的分布差异,并且分析其与肺癌临床病理特征的相关性。结果:ATM基因rs175048多态位点的AA、AT、TT 3种基因型的频率在病例组分别为24.9%、52.9%、22.2%,对照组为42.2%、42.2%、15.6%(均P<0.01);病例组等位基因A、T的频率为51.0%、49.0%,对照组为63.0%、37.0%(均P<0.01);TT基因型可能会增加、而AT基因型可能减少肺癌发病风险。rs175048单核苷酸多态位点与吸烟、年龄、性别和家族史等临床病理特征明显相关(均P<0.05)。结论:ATM基因rs175048位点单核苷酸多态性与肺癌的发生明显相关,且TT基因型可以增加肺癌发病的风险。
Objective: To explore the association between the single nucleotide polymorphism(SNP) of rs175048 in ataxia telangiectasia mutated(ATM) gene and lung cancer susceptibility in Han population. Methods: A total of 225 cases of blood samples from lung cancer patients treated in Hospital of Traditional Chinese Medicine of Hengyang City and the Affiliated First Hospital of Nanhua University from October 2015 to August 2016 were collected as case group, and 128 cases of blood samples from healthy people were collected as the control. The polymorphisms of ATM rs175048 of above mentioned participants were detected by using the SNP sensitive On/Off Switch technique. The genotypes and allele frequencies were analyzed to compare the distribution difference between case group and control group as well as its association to the clinical features of lung cancer. Results: The genotype frequencies of AA, AT and TT of ATM rs175048 were 24.9%, 52.9%, 22.2% in case group and 42.2%, 42.2%, 15.6% in control group, respectively(all P<0.01). Moreover, the frequencies of alleles A and T were 51.0%, 49.0% in case group, and 63.0%, 37.0% in control group(all P<0.01).Genotype TT might increase while genotype AT might decrease the risk of lung cancer. rs175048 SNP was significantly correlated with smoking, age, sex and family history(all P<0.05). Conclusion: rs175048 SNP is significantly associated with lung cancer, and TT genotype may increase the risk of lung cancer.
Objective: To explore the association between the single nucleotide polymorphism(SNP) of rs175048 in ataxia telangiectasia mutated(ATM) gene and lung cancer susceptibility in Han population. Methods: A total of 225 cases of blood samples from lung cancer patients treated in Hospital of Traditional Chinese Medicine of Hengyang City and the Affiliated First Hospital of Nanhua University from October 2015 to August 2016 were collected as case group, and 128 cases of blood samples from healthy people were collected as the control. The polymorphisms of ATM rs175048 of above mentioned participants were detected by using the SNP sensitive On/Off Switch technique. The genotypes and allele frequencies were analyzed to compare the distribution difference between case group and control group as well as its association to the clinical features of lung cancer. Results: The genotype frequencies of AA, AT and TT of ATM rs175048 were 24.9%, 52.9%, 22.2% in case group and 42.2%, 42.2%, 15.6% in control group, respectively(all P<0.01). Moreover, the frequencies of alleles A and T were 51.0%, 49.0% in case group, and 63.0%, 37.0% in control group(all P<0.01).Genotype TT might increase while genotype AT might decrease the risk of lung cancer. rs175048 SNP was significantly correlated with smoking, age, sex and family history(all P<0.05). Conclusion: rs175048 SNP is significantly associated with lung cancer, and TT genotype may increase the risk of lung cancer.
引文
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[14]SCHULTZ J,LORENZ P,IBRAHIM S M,et al.The functional-443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor[J].Mol Carcinog,2009,48(1):14-23.DOI:10.1002/mc.20452.
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[19]TANG L M,GUO Z F,XIAO L.A mutation sensitive switch assay for the deletion mutation of epidermal growth factor receptor in lung cancer[J].gene editing,2015,1(1):31-35.DOI:10.1166/gge.2015.1002.
[20]GUO Z F,GUO W S,XIAO L,et al.Discrimination of A1555G and C1494T point mutations in the mitochondrial 12S rRNA gene by on/off switch[J].Appl Biochem Biotechnol,2012,166(1):234-242.DOI:10.1007/s12010-011-9419-4.
[21]龚咏晴,董巍檑,陈方方,等.突变敏感性分子开关检测线粒体DNA A1555G位点的条件优化[J].临床检验杂志,2016,34(3):161-164.DOI:10.13602/j.cnki.jcls.2016.03.01.
[22]彭华,董巍檑,龚咏晴,等.ATM基因rs227060位点单核苷酸多态性与肺癌易感性的相关性[J].临床与病理杂志,2017,37(2):227-232.DOI:10.3978/j.issn.2095-6959.2017.02.002.
[23]YANG H S,SPITZ M R,STEWART D J,et al.ATM sequence variants associate with susceptibility to non-small cell lung cancer[J/OL].Int J Cancer,2007,121(10):2254-2259.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477817/.DOI:10.1002/ijc.22918.
[24]HSIA T C,TSAI C W,LIANG S J,et al.Effects of ataxia telangiectasia mutated(ATM)genotypes and smoking habits on lung cancer risk in Taiwan[J].Anticancer Res,2013,33(9):4067-4071.
[25]尧晓晴,孙世良,刘平,等.1213例肺癌患者的人群分布特点[J].职业卫生与病伤,2003,18(1):9-10.DOI:10.3969/j.issn.1006-172X.2003.01.004.
[2]JEREMIC B,GOMEZ-CAAMANO A,DUBINSKY P,et al.Radiation therapy in extensive stage small cell lung cancer[J/OL].Front Oncol,2017,7:169[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554488/.DOI:10.3389/fonc.2017.00169.
[3]TAN W L,JAIN A,TAKANO A,et al.Novel therapeutic targets on the horizon for lung cancer[J].Lancet Oncol,2016,17(8):347-362.DOI:10.1016/S1470-2045(16)30123-1.
[4]DHOLARIA B,HAMMOND W,SHREDERS A,et al.Emerging therapeutic agents for lung cancer[J/OL].J Hematol Oncol,2016,9(1):138[2019-02-22].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148871/.DOI:10.1186/s13045-016-0365-z.
[5]BELANI C P,MARTS S,SCHILLER J,et al.Women and lung cancer:epidemiology,tumor biology,and emerging trends in clinical research[J].Lung Cancer,2007,55(1):15-23.DOI:10.1016/j.lungcan.2006.09.008.
[6]KO Y C,CHENG L S,LEE C H,et al.Chinese food cooking and lung cancer in women nonsmokers[J].Am J Epidemiol,2000,151(2):140-147.DOI:10.1080/009841000157014
[7]PARKIN D M,BRAY F,FERLAY J,et al.Global cancer statistics,2002[J].CA Cancer J Clin,2005,55(2):74-108.DOI:10.1200/jco.2007.13.9303.
[8]KURZ E U,LEES-MILLER S P.DNA damage-induced activation of ATM and ATM-dependent signaling pathways[J].DNA Repair(Amst),2004,3(8/9):889-900.DOI:10.1016/j.dnarep.2004.03.029.
[9]DERHEIMER F A,KASTAN M B.Multiple roles of ATM in monitoring and maintaining DNA integrity[J].FEBS Lett,2010,584(17):3675-3681.DOI:10.1016/j.febslet.2010.05.031.
[10]单伟伟.ATM在孕激素治疗子宫内膜癌中的作用及其机制研究[D].上海:复旦大学,2013.
[11]GUO Z,KOZLOV S,LAVIN M F,et al.ATM activation by oxidative stress[J].Science,2010,330(6003):517-521.DOI:10.1126/science.1192912.
[12]TALUKDER K A,AZMI I J,AHMED K A,et al.Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells[J].Microb Pathog,2012,52(6):311-317.DOI:10.1016/j.micpath.2012.02.007.
[13]PROKOPCOVA J,KLEIBL Z,BANWELL C M,et al.The role of ATM in breast cancer development[J].Breast Cancer Res Treat,2007,104(2):121-128.DOI:10.1007/s10549-006-9406-6.
[14]SCHULTZ J,LORENZ P,IBRAHIM S M,et al.The functional-443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor[J].Mol Carcinog,2009,48(1):14-23.DOI:10.1002/mc.20452.
[15]FREY U H,HAUNER H,J?CKEL K H,et al.A novel promoter polymorphism in the human gene GNAS affects binding of transcription factor upstream stimulatory factor 1,Galphas protein expression and body weight regulation[J].Pharmacogenet Genomics,2008,18(2):141-151.DOI:10.1097/FPC.0b013e3282f49964.
[16]张金娥,池立伟,臧瑜.晚期肺癌患者的症状群研究进展[J].医学研究与教育,2016,33(5):49-52,73.DOI:10.3969/j.issn.1674-490X.2016.05.011.
[17]HOFFMAN R M,SANCHEZ R.Lung cancer screening[J].Med Clin North Am,2017,101(4):769-785.DOI:10.1016/j.mcna.2017.03.008.
[18]单艳,李志刚,姬卫国,等.VEGFR2基因V297I位点对贝伐珠单抗联合化疗一线治疗晚期非小细胞肺癌患者临床疗效的影响[J].中国肿瘤生物治疗杂志,2019,26(1):67-72.10.3872/j.issn.1007-385X.2019.01.011.
[19]TANG L M,GUO Z F,XIAO L.A mutation sensitive switch assay for the deletion mutation of epidermal growth factor receptor in lung cancer[J].gene editing,2015,1(1):31-35.DOI:10.1166/gge.2015.1002.
[20]GUO Z F,GUO W S,XIAO L,et al.Discrimination of A1555G and C1494T point mutations in the mitochondrial 12S rRNA gene by on/off switch[J].Appl Biochem Biotechnol,2012,166(1):234-242.DOI:10.1007/s12010-011-9419-4.
[21]龚咏晴,董巍檑,陈方方,等.突变敏感性分子开关检测线粒体DNA A1555G位点的条件优化[J].临床检验杂志,2016,34(3):161-164.DOI:10.13602/j.cnki.jcls.2016.03.01.
[22]彭华,董巍檑,龚咏晴,等.ATM基因rs227060位点单核苷酸多态性与肺癌易感性的相关性[J].临床与病理杂志,2017,37(2):227-232.DOI:10.3978/j.issn.2095-6959.2017.02.002.
[23]YANG H S,SPITZ M R,STEWART D J,et al.ATM sequence variants associate with susceptibility to non-small cell lung cancer[J/OL].Int J Cancer,2007,121(10):2254-2259.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477817/.DOI:10.1002/ijc.22918.
[24]HSIA T C,TSAI C W,LIANG S J,et al.Effects of ataxia telangiectasia mutated(ATM)genotypes and smoking habits on lung cancer risk in Taiwan[J].Anticancer Res,2013,33(9):4067-4071.
[25]尧晓晴,孙世良,刘平,等.1213例肺癌患者的人群分布特点[J].职业卫生与病伤,2003,18(1):9-10.DOI:10.3969/j.issn.1006-172X.2003.01.004.