Abstract
Survivin is an inhibitor of apoptosis protein and has a crucial role in the development of cancer. The survivin −31G>C (rs9904341) promoter polymorphism influences survivin expression and has been implicated in cancer risk. However, conflicting results have been published from studies on the association between survivin −31G>C polymorphism and the risk of cancer. To clarify the role of this polymorphism in cancer, we performed a meta-analysis of all available and relevant published studies, involving a total of 3485 cancer patients and 3964 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results indicated that the variant genotypes were associated with a significantly increased cancer risk (CC vs GG: OR=1.58, 95% CI=1.20–2.10; CC/GC vs GG: OR=1.23, 95% CI=1.00–1.51; CC vs GG/GC: OR=1.51, 95% CI=1.23–1.85). In the stratified analyses, significantly increased risk was associated with the Asian populations (CC vs GG: OR=1.67, 95% CI=1.16–2.40; CC vs GG/GC: OR=1.50, 95% CI=1.17–1.91). We also performed the analyses by cancer type, and no statistical association was observed. The results suggest that the survivin −31G>C promoter polymorphism might be associated with an increased risk of cancer, especially in the Asian populations.
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References
Pharoah PD, Dunning AM, Ponder BA, Easton DF : Association studies for finding cancer-susceptibility genetic variants. Nat Rev 2004; 4: 850–860.
Mondello C, Scovassi AI : Apoptosis: a way to maintain healthy individuals. Subcell Biochem 2010; 50: 307–323.
Raff M : Cell suicide for beginners. Nature 1998; 396: 119–122.
Delhalle S, Duvoix A, Schnekenburger M, Morceau F, Dicato M, Diederich M : An introduction to the molecular mechanisms of apoptosis. Ann NY Acad Sci 2003; 1010: 1–8.
Degterev A, Boyce M, Yuan J : A decade of caspases. Oncogene 2003; 22: 8543–8567.
Hajra KM, Liu JR : Apoptosome dysfunction in human cancer. Apoptosis 2004; 9: 691–704.
Ambrosini G, Adida C, Altieri DC : A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3: 917–921.
Li F, Ambrosini G, Chu EY et al: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998; 396: 580–584.
Altieri DC : The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 2001; 7: 542–547.
Altieri DC : Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer 2008; 8: 61–70.
Ambrosini G, Adida C, Sirugo G, Altieri DC : Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem 1998; 273: 11177–11182.
Xu Y, Fang F, Ludewig G, Jones G, Jones D : A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells. DNA Cell Biol 2004; 23: 527–537.
Jang JS, Kim KM, Kang KH et al: Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer 2008; 60: 31–39.
Borbely AA, Murvai M, Szarka K et al: Survivin promoter polymorphism and cervical carcinogenesis. J Clin Pathol 2007; 60: 303–306.
Kawata N, Tsuchiya N, Horikawa Y et al: Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility. Int J Cancer 2010; 129: 1872–1880.
Borges BD, Burbano RR, Harada ML : Survivin −31C/G polymorphism and gastric cancer risk in a Brazilian population. Clin Exp Med 2011; 11: 189–193.
Theodoropoulos GE, Michalopoulos NV, Panoussopoulos SG, Taka S, Gazouli M : Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics. Pancreas 2010; 39: 976–980.
Wang YH, Chiou HY, Lin CT et al: Association between survivin gene promoter −31 C/G polymorphism and urothelial carcinoma risk in Taiwanese population. Urology 2009; 73: 670–674.
Gazouli M, Tzanakis N, Rallis G et al: Survivin −31G/C promoter polymorphism and sporadic colorectal cancer. Int J Colorectal Dis 2009; 24: 145–150.
Yang X, Xiong G, Chen X et al: Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2009; 135: 1341–1349.
Upadhyay R, Khurana R, Kumar S, Ghoshal UC, Mittal B : Role of survivin gene promoter polymorphism (−31G>C) in susceptibility and survival of esophageal cancer in Northern India. Ann Surg Oncol 2011; 18: 880–887.
Cheng ZJ, Hu LH, Huang SJ : [Correlation of −31G/C polymorphisms of survivin promoter to tumorigenesis of gastric carcinoma]. Ai Zheng 2008; 27: 258–263.
Yang L, Zhu H, Zhou B et al: The association between the survivin C-31G polymorphism and gastric cancer risk in a Chinese population. Dig Dis Sci 2009; 54: 1021–1028.
Bayram S, Akkiz H, Bekar A, Akgollu E : The association between the survivin −31G/C promoter polymorphism and hepatocellular carcinoma risk in a Turkish population. Cancer Epidemiol 2011; 35: 555–559.
Ma F, Zhang H, Zhai Y et al: Functional polymorphism −31C/G in the promoter of BIRC5 gene and risk of nasopharyngeal carcinoma among Chinese. PLoS One 2011; 6: e16748.
Mantel N, Haenszel W : Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–748.
DerSimonian R, Laird N : Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.
Wang YH, Chen DJ, Yi TN, Liu XH : The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue. Saudi Med J 2010; 31: 1331–1336.
Wang H, Holloway MP, Ma L et al: Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. J Biol Chem 2010; 285: 36129–36137.
Krepela E, Dankova P, Moravcikova E et al: Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma. Int J Oncol 2009; 35: 1449–1462.
Farnebo L, Jerhammar F, Vainikka L, Grenman R, Norberg-Spaak L, Roberg K : Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines. Oncol Rep 2008; 20: 453–461.
Wagner M, Schmelz K, Dorken B, Tamm I : Epigenetic and genetic analysis of the survivin promoter in acute myeloid leukemia. Leuk Res 2008; 32: 1054–1060.
Boidot R, Vegran F, Jacob D et al: The expression of BIRC5 is correlated with loss of specific chromosomal regions in breast carcinomas. Genes Chromosomes Cancer 2008; 47: 299–308.
Vegran F, Boidot R, Oudin C, Defrain C, Rebucci M, Lizard-Nacol S : Association of p53 gene alterations with the expression of antiapoptotic survivin splice variants in breast cancer. Oncogene 2007; 26: 290–297.
Floyd HS, Jennings-Gee JE, Kock ND, Miller MS : Genetic and epigenetic alterations in lung tumors from bitransgenic Ki-rasG12C expressing mice. Mol Carcinog 2006; 45: 506–517.
Nakano J, Huang CL, Liu D, Ueno M, Sumitomo S, Yokomise H : Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer. Int J Oncol 2005; 27: 1215–1221.
Teodoridis JM, Hall J, Marsh S et al: CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 2005; 65: 8961–8967.
Kimura M, Okano Y : [Aurora kinases and cancer]. Gan To Kagaku Ryoho 2005; 32: 1–5.
Saitoh Y, Yaginuma Y, Ishikawa M : Analysis of Bcl-2, Bax and Survivin genes in uterine cancer. Int J Oncol 1999; 15: 137–141.
Boidot R, Vegran F, Jacob D et al: The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism. Oncogene 2010; 29: 2577–2584.
Farnebo L, Jedlinski A, Ansell A et al: Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines. Int J Mol Med 2009; 24: 549–556.
Loof J, Pfeifer D, Adell G, Sun XF : Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy. Radiother Oncol 2009; 92: 215–220.
Yang X, Xiong G, Chen X et al: Survivin expression in esophageal cancer: correlation with p53 mutations and promoter polymorphism. Dis Esophagus 2009; 22: 223–230.
Han CH, Wei Q, Lu KK, Liu Z, Mills GB, Wang LE : Polymorphisms in the survivin promoter are associated with age of onset of ovarian cancer. Int J Clin Exp Med 2009; 2: 289–299.
Duffy MJ, O’Donovan N, Brennan DJ, Gallagher WM, Ryan BM : Survivin: a promising tumor biomarker. Cancer Lett 2007; 249: 49–60.
Melet A, Song K, Bucur O, Jagani Z, Grassian AR, Khosravi-Far R : Apoptotic pathways in tumor progression and therapy. Adv Exp Med Biol 2008; 615: 47–79.
Fukuda S, Pelus LM : Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther 2006; 5: 1087–1098.
Altieri DC : Validating survivin as a cancer therapeutic target. Nat Rev Cancer 2003; 3: 46–54.
Reed JC : The Survivin saga goes in vivo. J Clin Invest 2001; 108: 965–969.
Tamm I, Wang Y, Sausville E et al: IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58: 5315–5320.
Shin S, Sung BJ, Cho YS et al: An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 2001; 40: 1117–1123.
Sun C, Nettesheim D, Liu Z, Olejniczak ET : Solution structure of human survivin and its binding interface with Smac/Diablo. Biochemistry 2005; 44: 11–17.
Liu T, Brouha B, Grossman D : Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells. Oncogene 2004; 23: 39–48.
Kim PJ, Plescia J, Clevers H, Fearon ER, Altieri DC : Survivin and molecular pathogenesis of colorectal cancer. Lancet 2003; 362: 205–209.
Peng XH, Karna P, Cao Z, Jiang BH, Zhou M, Yang L : Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 2006; 281: 25903–25914.
Li F, Altieri DC : The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res 1999; 59: 3143–3151.
Otaki M, Hatano M, Kobayashi K, Ogasawara T, Kuriyama T, Tokuhisa T : Cell cycle-dependent regulation of TIAP/m-survivin expression. Biochim Biophys Acta 2000; 1493: 188–194.
Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K : A comprehensive review of genetic association studies. Genet Med 2002; 4: 45–61.
Wang Y, Yang H, Li H et al: Association between X-ray repair cross complementing group 1 codon 399 and 194 polymorphisms and lung cancer risk: a meta-analysis. Cancer Lett 2009; 285: 134–140.
Acknowledgements
This work was supported by the China Natural Science Foundation (30872657 and 81072078), Natural Science Foundation of Jiangsu Province (2008475 and 2010580), Scientific Program of Ministry of Health (W2011BX009), Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
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Wang, X., Huang, L., Xu, Y. et al. Association between survivin −31G>C promoter polymorphism and cancer risk: a meta-analysis. Eur J Hum Genet 20, 790–795 (2012). https://doi.org/10.1038/ejhg.2011.276
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DOI: https://doi.org/10.1038/ejhg.2011.276
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