MDM2基因多态性与食管癌 胃癌易感性的关系Meta分析
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摘要
目的探求鼠双微体基因2(Murine Doubleminute 2,MDM2)基因多态性与食管癌、胃癌易感性的关系。方法运用计算机检索PubMed、Embase、中国知网、万方、维普数据库,收集有关MDM2多态性与食管癌、胃癌易感性的病例对照研究文献,纳入符合标准的文献,提取数据进行Meta分析。结果共有16篇文献符合条件并纳入研究。Meta分析结果表明:显性基因型(TT+TG)的个体对食管癌/胃癌的易感性降低,TT+TG vs GG:OR=0.73,95%CI=(0.59,0.91),P<0.001。与变异纯合子(GG)基因型相比,野生纯合子(TT)基因型的个体中患食管癌、胃癌的风险降低,TT vs GG:食管癌易感性OR=0.79,95%CI=(0.68,0.93),P=0.005,胃癌易感性OR=0.52,95%CI=(0.38,0.72),P<0.001;变异杂合子(TG)基因型的个体中患胃癌的风险降低,TG vs GG:食管癌易感性OR=0.74,95%CI=(0.48,1.14),P=0.173、胃癌易感性OR=0.62,95%CI=(0.50,0.75),P <0.001;而野生纯合子(TT)基因型与变异杂合子(TG)基因型相比,个体患食管癌、胃癌的风险差别无统计学意义,TT vs TG:食管癌易感性OR=1.01,95%CI=(0.80,1.27),P=0.966、胃癌易感性OR=0.85,95%CI=(0.67,1.08),P=0.193。结论 MDM2基因多态性与食管癌、胃癌易感性相关,MDM2显性基因型(TT、TG)与食管癌、胃癌患病易感性的降低有关。
Objective To investigate the association between MDM2 polymorphism and susceptibility of esophageal carcinoma and gastric carcinoma. Methods We used PubMed,Embase,CNKI,Wanfang and the VIP database to search the articles which focused on the association between MDM2 polymorphism and esophageal squamous cell carcinoma or gastric carcinoma. The study design of the article was case-control study. Pooled results were showed by the odds ratio(OR) and 95% confidence interval(CI). Results Meta-analysis showed that Dominant genotype(TT,TG) of MDM2 could reduce the risk of the esophageal squamous cell carcinoma or gastric cancer,TT + TG vs. GG: OR = 0.73,95%CI =(0.59,0.91),P < 0.001. Compared with mutant homozygote(GG),wild homozygote(TT) could reduce the risk of the esophageal squamous cell carcinoma and gastric cancer,TT vs. GG: esophageal squamous cell carcinoma OR = 0.79,95%CI =(0.68,0.93),P = 0.005; gastric cancer OR = 0.52,95% CI =(0.38,0.72),P < 0.001;mutant heterozygote(TG) could only reduce the risk of the gastric cancer,TG vs. GG: esophageal squamous cell carcinoma OR = 0.74,95% CI =(0.48,1. 14),P = 0.173; gastric cancer OR = 0.62,95% CI =(0.50,0.75),P < 0.001.However,there was no statistical significance in TT vs TG: esophageal squamous cell carcinoma OR = 1. 01,95%CI =(0.80,1. 27),P = 0.966; gastric cancer OR = 0.85,95% CI =(0.67,1. 08),P = 0.193. Conclusion The MDM2 genic polymorphism may be impact the risk of esophageal squamous cell carcinoma and gastric cancer. Dominant genes(TT,TG) could reduce the risk of the esophageal squamous cell carcinoma and gastric cancer.
Objective To investigate the association between MDM2 polymorphism and susceptibility of esophageal carcinoma and gastric carcinoma. Methods We used PubMed,Embase,CNKI,Wanfang and the VIP database to search the articles which focused on the association between MDM2 polymorphism and esophageal squamous cell carcinoma or gastric carcinoma. The study design of the article was case-control study. Pooled results were showed by the odds ratio(OR) and 95% confidence interval(CI). Results Meta-analysis showed that Dominant genotype(TT,TG) of MDM2 could reduce the risk of the esophageal squamous cell carcinoma or gastric cancer,TT + TG vs. GG: OR = 0.73,95%CI =(0.59,0.91),P < 0.001. Compared with mutant homozygote(GG),wild homozygote(TT) could reduce the risk of the esophageal squamous cell carcinoma and gastric cancer,TT vs. GG: esophageal squamous cell carcinoma OR = 0.79,95%CI =(0.68,0.93),P = 0.005; gastric cancer OR = 0.52,95% CI =(0.38,0.72),P < 0.001;mutant heterozygote(TG) could only reduce the risk of the gastric cancer,TG vs. GG: esophageal squamous cell carcinoma OR = 0.74,95% CI =(0.48,1. 14),P = 0.173; gastric cancer OR = 0.62,95% CI =(0.50,0.75),P < 0.001.However,there was no statistical significance in TT vs TG: esophageal squamous cell carcinoma OR = 1. 01,95%CI =(0.80,1. 27),P = 0.966; gastric cancer OR = 0.85,95% CI =(0.67,1. 08),P = 0.193. Conclusion The MDM2 genic polymorphism may be impact the risk of esophageal squamous cell carcinoma and gastric cancer. Dominant genes(TT,TG) could reduce the risk of the esophageal squamous cell carcinoma and gastric cancer.
引文
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[18]Zhang L,Zhu Z,Wu H,et al.Association between SNP309 and del1518 Polymorphism in MDM2 Homologue and Esophageal Squamous Cell Carcinoma Risk in Chinese Population of Shandong Province[J].Ann Clin Lab Sci,2015,45(4):433-437.
[19]Yang M,Guo Y,Zhang X,et al.Interaction of P53Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer[J].Carcinogenesis,2007,28(9):1996-2001.DOI:10.1093/carcin/bgm168.
[20]尔丽绵,张立玮,牛巍巍,等.小鼠双微体基因309T/G多态性及幽门螺杆菌感染与贲门癌的发病关联[J].临床荟萃,2009,24(18):1594-1597.
[21]Ohmiya N,Taguchi A,Mabuchi N,et al.MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis[J].JClin Oncol,2006,24(27):4434-4440.DOI:10.1200/JCO.2005.04.1459.
[22]Cho YG,Choi BJ,Song JH,et al.No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients[J].Neoplasma,2008,55(3):256-260.
[23]Wang X,Yang J,Ho B,et al.Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter,is associated with gastric cancer susceptibility in Chinese patients[J].Helicobacter,2009,14(5):114-119.DOI:10.1111/j.1523-5378.2009.00712.x.
[24]李玉琴.幽门螺杆菌、MDM2SNP309基因多态性的交互作用与胃癌易感性的相关研究[D].南京:南京医科大学,2010.
[25]张丽.中国汉族人群单核苷酸多态性与幽门螺杆菌相关性胃癌的关系研究[D].重庆:重庆医科大学,2011.
[26]Moradi MT,Salehi Z,Asl SF,et al.Helicobacter pylori infection and MDM2 SNP309 association with gastric cancer susceptibility[J].Genet Test Mol Biomarkers,2013,17(11):794-798.DOI:10.1089/gtmb.2013.0173.
[27]Pan X,Li Y,Feng J,et al.A functional polymorphism T309G in MDM2 gene promoter,intensified by Helicobacter pylori lipopolysaccharide,is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients[J].BMC Cancer,2013,13:126.DOI:10.1186/1471-2407-13-126.
[28]阚清鹏,王欣宇,栾厦,等.Mdm2转录产物对p53调节作用的研究进展[J].医学综述,2017,23(11):2090-2093.DOI:10.3969/j.issn.1006-2084.2017.11.003.
[2]彭智.GLOBCAN胃癌流行病学数据解读[J/CD].肿瘤综合治疗电子杂志,2018,4(4):63-65.
[3]Zeng X,Chen L,Jost CA,et al.MDM2 suppresses p73function without promoting p73 degradation[J].Mol Cell Biol,1999,19(5):3257-3266.
[4]Bond GL,Hu W,Bond EE,et al.A single nucleotide polymorphism in the MDM2 promoter attenuates the p53tumor suppressor pathway and accelerates tumor formation in humans[J].Cell,2004,119(5):591-602.DOI:10.1016/j.cell.2004.11.022.
[5]季雪梅,李小燕.mdm2基因在肿瘤中的研究进展[J].昆明医学院学报,2009,30(S1):98-102.
[6]张鑫,康凯夫.小鼠双微体2基因在肿瘤中作用的研究进展[J].医学综述,2009,15(22):3363-3365.DOI:10.3969/j.issn.1006-2084.2009.22.002.
[7]李灵敏,冀春萱.P53、P21~(WAFI)、MDM2及BAX在食管鳞癌中的表达和相关性分析[J].解剖学杂志,2005,28(1):26-28,122.
[8]薄爱华,张晓丽,邢立强,等.MDM2与p21、p53在胃癌、食管癌中表达的相关性研究[J].实用癌症杂志,2001,16(1):34-35,59.DOI:10.3969/j.issn.1001-5930.2001.01.013.
[9]王志发,薛月梅,张旭.癌基因MDM2研究[J].黑龙江医学,2013,37(4):244-246.DOI:10.3969/j.issn.1004-5775.2013.04.002.
[10]Oliner JD,Kinzler KW,Meltzer PS,et al.Amplification of a gene encoding a p53-associated protein in human sarcomas[J].Nature,1992,358(6381):80-83.DOI:10.1038/358080a0.
[11]GA Wells BSDO.The Newcastle-Ottawa Scale(NOS)for assessing the quality of nonrandomised studies in meta-analyses.Available at:http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.(15 March2018,date last accessed).
[12]Hong Y,Miao X,Zhang X,et al.The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma[J].Cancer Res,2005,65(20):9582-9587.DOI:10.1158/0008-5472.CAN-05-1460.
[13]曹延延,张秀凤,郭炜,等.MDM2基因多态性与食管鳞癌、贲门腺癌易感性的关系[J].肿瘤,2007,27(8):628-632.DOI:10.3781/j.issn.1000-7431.2007.08.009.
[14]Liu G,Cescon DW,Zhai R,et al.p53 Arg72Pro,MDM2T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma[J].Dis Esophagus,2010,23(1):36-39.DOI:10.1111/j.1442-2050.2009.00960.x.
[15]Ma J,Zhang J,Ning T,et al.Association of genetic polymorphisms in MDM2,PTEN and P53 with risk of esophageal squamous cell carcinoma[J].J Hum Genet,2012,57(4):261-264.DOI:10.1038/jhg.2012.15.
[16]尔丽绵,张立玮,牛巍巍,等.MDM2-309多态与食管、胃及其双原发癌的发病关联[J].现代预防医学,2012,39(13):3342-3344.
[17]Yang J,Liu B,Li W,et al.Association of p53 and MDM2 polymorphisms with risk of human papillomavirus(HPV)-related esophageal squamous cell carcinoma(ESCC)[J].Cancer Epidemiol,2013,37(5):629-633.DOI:10.1016/j.canep.2013.06.001.
[18]Zhang L,Zhu Z,Wu H,et al.Association between SNP309 and del1518 Polymorphism in MDM2 Homologue and Esophageal Squamous Cell Carcinoma Risk in Chinese Population of Shandong Province[J].Ann Clin Lab Sci,2015,45(4):433-437.
[19]Yang M,Guo Y,Zhang X,et al.Interaction of P53Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer[J].Carcinogenesis,2007,28(9):1996-2001.DOI:10.1093/carcin/bgm168.
[20]尔丽绵,张立玮,牛巍巍,等.小鼠双微体基因309T/G多态性及幽门螺杆菌感染与贲门癌的发病关联[J].临床荟萃,2009,24(18):1594-1597.
[21]Ohmiya N,Taguchi A,Mabuchi N,et al.MDM2 promoter polymorphism is associated with both an increased susceptibility to gastric carcinoma and poor prognosis[J].JClin Oncol,2006,24(27):4434-4440.DOI:10.1200/JCO.2005.04.1459.
[22]Cho YG,Choi BJ,Song JH,et al.No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients[J].Neoplasma,2008,55(3):256-260.
[23]Wang X,Yang J,Ho B,et al.Interaction of Helicobacter pylori with genetic variants in the MDM2 promoter,is associated with gastric cancer susceptibility in Chinese patients[J].Helicobacter,2009,14(5):114-119.DOI:10.1111/j.1523-5378.2009.00712.x.
[24]李玉琴.幽门螺杆菌、MDM2SNP309基因多态性的交互作用与胃癌易感性的相关研究[D].南京:南京医科大学,2010.
[25]张丽.中国汉族人群单核苷酸多态性与幽门螺杆菌相关性胃癌的关系研究[D].重庆:重庆医科大学,2011.
[26]Moradi MT,Salehi Z,Asl SF,et al.Helicobacter pylori infection and MDM2 SNP309 association with gastric cancer susceptibility[J].Genet Test Mol Biomarkers,2013,17(11):794-798.DOI:10.1089/gtmb.2013.0173.
[27]Pan X,Li Y,Feng J,et al.A functional polymorphism T309G in MDM2 gene promoter,intensified by Helicobacter pylori lipopolysaccharide,is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients[J].BMC Cancer,2013,13:126.DOI:10.1186/1471-2407-13-126.
[28]阚清鹏,王欣宇,栾厦,等.Mdm2转录产物对p53调节作用的研究进展[J].医学综述,2017,23(11):2090-2093.DOI:10.3969/j.issn.1006-2084.2017.11.003.