期刊文献+

MKK4基因启动子区遗传变异与中国南方人群肺癌易感性的相关性研究 被引量:1

The association between a genetic variant in MKK4 gene promoter and lung cancer risk in Southern Chinese population
原文传递
导出
摘要 目的:探讨丝裂原活化蛋白激酶激酶4(mitogen-activated protein kinase kinase4,MKK4)基因启动子区单核苷酸多态性与中国南方人群肺癌发病风险的关系。方法:采用病例对照研究方法,收集800例肺癌病例和900例正常对照,采用TaqMan技术检测MKK4基因启动子区多态位点rs3826392(-1304T>G)的基因型。应用SAS9.3软件分析其与肺癌易感性的相关性。结果:MKK4基因启动子区-1304T>G基因型在对照组中的频率分布符合Hardy-Weinberg平衡(P=0.149),其在病例组和对照组的分布差异有统计学意义(P=0.001);与携带TT基因型个体相比,携带TG杂合子的个体患肺癌的风险下降25%[校正比值比(oddratio,OR)=0.75,95%可信区间(confidence interval,CI)=0.58~0.97],而携带GG变异纯合子者患肺癌的风险下降45%(校正OR=0.55,95%CI=0.33~0.94);随着变异型等位基因G的个数增加,肺癌发病风险逐步降低(P趋势<0.001)。结论:MKK4基因启动子区-1304T>G基因遗传变异可能降低肺癌发病风险。 Objective: To investigate the association between the single nucleotide polymorphism (SNP) of mitogen-activated protein kinase kinase 4 (MKK4) promoter and the risk of lung cancer development in Southern Chinese population. Methods: A hospital-based case-control study including 800 cases of lung cancer and 900 healthy controls was conducted. TaqMan assay was used to test the SNP of rs3826392 (-1304T〉G) in MKK4 promoter, and the software SAS 9.13 was used to analyze the association of MKK4 polymorphism and the susceptibility of lung cancer. Results: The observed genotype frequency of -1304T〉 G in MKK4 promoter was appropriate for Hardy-Weinberg equilibrium in the healthy controls (P = 0.149). The distribution of genotypes was significantly different between the cases of lung cancer and the healthy controls (P=0.001). Compared with homozygous genotype (TT), the risk for lung cancer was decreased by 25% in the carriers of heterozygous genotype (TG) [adjusted odd ratio (OR) = 0.75, 95% confidence interval (CI) = 0.58-0.97)], and the risk for lung cancer in carriers of GG homozygote was decreased by 45% (adjusted OR = 0.55, 95% CI = 0.33-0.94). There was a significantly decreased trend in the risk for lung cancer along with the increased number of mutation-typic G allele (Ptrend〈0.001). Conclusion: These findings demonstrate that -1304T〉G genotype in promoter region of MKK4 gene may contribute to the decreased risk of lung cancer.
出处 《肿瘤》 CAS CSCD 北大核心 2011年第12期1082-1086,共5页 Tumor
基金 国家自然科学基金资助项目(编号:30972540 81072366) 广东省高等学校高层次人才资助项目(编号:粤教师函[2010]79-1) 广东省科技计划项目(编号:2008B060600008)
关键词 肺肿瘤 有丝分裂原激活蛋白激酶激酶类 多态现象 单核苷酸 疾病易感性 Lung neoplasms Mitogen-activated protein kinase kinases Polymorphism, singlenucleotide Disease susceptibility
  • 相关文献

参考文献17

  • 1CUENDA A.Mitogen-activated protein kinase kinase 4 (MKK4)[J].Int J Biochem Cell Biol,2000,32(6):581-587.
  • 2WHITMARSH A J,DAVIS R J.Role of mitogenactivated protein kinase kinase 4 in cancer[J].Oncogene,2007,26(22):3172-3184.
  • 3WANG L,PAN Y,DAI J L.Evidence of MKK4 prooncogenic activity in breast and pancreatic tumors[J].Oncogene,2004,23(35):5978-5985.
  • 4HUANG C,HUANG K,WANG C,et al.Overexpression of mitogen-activated protein kinase kinase 4 and nuclear factor-kappaB in laryngeal squamous cell carcinoma:a potential indicator for poor prognosis[J].Oncol Rep,2009,22(1):89-95.
  • 5WEI Y,WANG L,LAN P,et al.The association between-1304T > G polymorphism in the promoter of MKK4 gene and the risk of sporadic colorectal cancer in southern Chinese population[J].Int J Cancer,2009,125(8):1876-1883.
  • 6IORDANOV M S,MAGUN B E.Loss of cellular K+ mimics ribotoxic stress.Inhibition of protein synthesis and activation of the stress kinases SEK1/MKK4,stress-activated protein kinase/c-Jun NH2-terminal kinase 1,and p38/HOG1 by palytoxin[J].J Biol Chem,1 998,273(6):3528-3534.
  • 7ZHOU BEI-FAN2Cooperative Meta-Analysis Group of the Working Group on Obesity in China.Predictive Values of Body Mass Index and Waist Circumference for Risk Factors of Certain Related Diseases in Chinese Adults - Study on Optimal Cut-off Points of Body Mass Index and Waist Circumference in Chinese Adults[J].Biomedical and Environmental Sciences,2002,15(1):83-96. 被引量:253
  • 8WU C W,LI A F,CHIC W,et al.Human gastric cancer kinase profile andprognostic significance of MKK4 kinase[J].Am J Pathol,2000,156(6):2007-2015.
  • 9CHAE K S,RYU B K,LEE M G,et al.Expression and mutation analyses of MKK4,a candidate tumour suppressor gene encoded by chromosome 17p,in human gastric adenocarcinoma[J].Eur J Cancer,2002,38(15):2048-2057.
  • 10CUNNINGHAM S C,GALLMEIER E,HUCL T,et al.Targeted deletion of MKK4 in cancer cells:a detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss[J].Cancer Res,2006,66(11):5560-5564.

二级参考文献12

  • 1TOURNIER C, WHITMARSH A J, CAVANAGH J, et al. The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases [J]. Mol Cell Biol,1999,19(2) : 1569-1581.
  • 2WANG L, PAN Y, DAI JL. Evidence of MKK4 pro-oncogenic activity in breast and pancreatic tumors [J].Oncogene, 2004,23 (35) : 5978 5985.
  • 3WU C W, LI A F, CHIC W, et al. Human gastric cancer kinase profile and prognostic significance of MKK4 kinase [ J ]. Am J Pathol,2000,156 ( 6 ) :2007-2015.
  • 4SETHI G, AHN K S, XIA D, et al. Targeted deletion of MKK4 gene potentiates TNF-induced apoptosis through the down-regulation of NF- {kappa} B activation and NF- {kappa} B-regulated anti-apoptotic gene products [J]. J Immunol, 2007,179 ( 3 ) : 1926- 1933.
  • 5XIA D, SRINIVAS H, AHN Y H, et al. Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expres- sion through an NF kappa B-dependent pathway [ J ]. J Biol Chem, 2007,282(6) : 3507-3519.
  • 6TENG DH, PERRY WL, HOGAN JK, et al. Human mitogen- activated protein kinase kinase 4 as a candidate tumor suppressor [J]. Cancer Res,1997,57(19) : 4177-4182.
  • 7CUNNINGHAM S C, KAMANGAR F, KIM M P, et al. MKK4 status predicts survival after resection of gastric adenocarcinoma [J]. Arch Surg ,2006 ,141 ( 11 ) :1095-1099.
  • 8STARK A M, TONGERS K, MAASS N, et al. Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases [ J ]. J Cancer Res Clin Oncol,2005,131 ( 3 ) : 191-198.
  • 9DERIJARD B, RAINGEAUD J, BARRETT T, et al. Independent human MAP kinase signal transduction pathways defined by MEK and MKK isoforms [ J ]. Science, 1995,267 ( 5198 ) : 682-685.
  • 10LIN A, MINDEN A, MARTINETTO H, et al. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2 [ J ]. Science, 1995,268 (5208) : 286-290.

共引文献256

同被引文献27

  • 1Steeg PS,de la Rosa A, Flatow U, et al. Nm23 and breast cancer metastasis [ J ]i Breast CanCer Res Treat, 1993,25 (2) : 172-187.
  • 2Yoshida BA,Sokoloff MM, Welch DR, et al. Metastasis-suppressor genes:a review and perspective on an emerging field [ J]. J Nail Cancer Inst,2000,92 (21) . 717-1730.
  • 3Takekawa M, Tatebayashi K, Saito H. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases [ J]. Mol Ce11,2005,18 (3) : 295 -306.
  • 4Maruyama J, Naguro I, Takeda K, et al. Stress-activated MAP kinase cascades in cellular seneacence[ J]. Curr Med Chem,2009, 16(10) :1229-1235.
  • 5Owen GR, Achilonu I, Dirr HW. High yield purification of JNK113 and active by in vitro reconstitution of the MEKK1-MKK4-JNK- MAPK phosphorylation cascade [ J ]. Protein Expr Purif, 2013,87 (2) :87-99.
  • 6Das KC, Muniyappa H. c-Jun-NH2 terminal kinase (JNK) -media- tes AP-1 activation by thioredoxin : Phosphorylation of cJun, JunB, and Fra-1 [ J ]. Mol Cell Biochem ,2010,337 (1/2) :53-63.
  • 7Taylor JL, Szmulewitz RZ, Lotan T, et aL New paradigms for the function of JNKK1/MKK4 in controlling growth of disseminated cancer cells[ ] ]. Cancer Letters ,2008,272 ( 1 ) : 12-22.
  • 8Brancho D, Tanaka N, Jaeschke A, et al. Mechanism of p38 MAP kinase activation in vivo [ J ]. Genes Dev ,2003 ,17 (16) : 1969-1978.
  • 9Finegan KG, Toumier C. The mitogen-activated protein kinases kinases 4 has a pro-oncogenic role in skin cancer[ J]. Cancer Res, 2010,70(14) :5797-5806.
  • 10Dolado I,Swat A ,Ajenjo N ,et al. p38oc MAP kinase as a sensor of reactive oxygen species in tumorigenesis [ J ]. Cancer Cell ,2007,11 (2) : 191-205.

引证文献1

二级引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部