Abstract
Purpose
Survivin is undetectable in normal adult tissues, but has been shown to be overexpressed in various cancers and has been regarded as a marker of malignancy. Polymorphisms which increase the expression of survivin are potential risk factors for esophageal carcinogenesis. The aim of this study is to genotype the survivin promoter polymorphisms namely −31G/C, −241T/C, −625G/C, and −644T/C in esophageal squamous cell cancer patients and controls and to identify a possible association between individual genetic variation and susceptibility to esophageal squamous cell carcinoma (ESCC).
Methods
The expression of survivin in cancer tissues was detected by semiquantitative RT-PCR. A total of 221 Chinese ESCC patients and 268 cancer-free controls were evaluated for the four polymorphisms in survivin promoter. Polymorphisms were identified using the PCR–RFLP technique (−31G/C, −241T/C) or primer-introduced restriction analysis-PCR assay (−644T/C, −625G/C).
Results
Compared with the −625GG genotype, the −625CC genotype was associated with significant elevated risk of ESCC (OR = 2.404, 95% CI = 1.342–4.307). Furthermore, significant difference in survivin expression in esophageal squamous cell cancer tissues was found between subgroups with different −625G/C variants. When we examined the combined effect of the survivin promoter polymorphisms, the haplotypes constructed of −644T/C-−625G/C-−31G/C revealed significant associations with ESCC (global P = 0.0034). −644T-−625C-−31C was a risk haplotype for ESCC (P < 0.001) and −644T-−625G-−31C was a protective haplotype (P = 0.004).
Conclusions
Our finding suggested that survivin promoter polymorphisms −625G/C might influence the susceptibility to ESCC in the Chinese population, maybe by influencing survivin expression.
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References
Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC (1998) Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 152:43–49
Altieri DC (2001) The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 7:542–547. doi:10.1016/S1471-4914(01)02243-2
Altieri DC (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22:8581–8589. doi:10.1038/sj.onc.1207113
Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921. doi:10.1038/nm0897-917
Ardlie KG, Kruglyak L, Seielstad M (2002) Patterns of linkage disequilibrium in the human genome. Nat Rev Genet 3:299–309. doi:10.1038/nrg777
Borbely AA, Murvai M, Szarka K, Konya J, Gergely L, Hernadi Z, Veress G (2007) Survivin promoter polymorphism and cervical carcinogenesis. J Clin Pathol 60:303–306. doi:10.1136/jcp.2006.037804
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229. doi:10.1126/science.1069424
Ikeguchi M, Kaibara N (2002) Survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer 87:883–887. doi:10.1038/sj.bjc.6600546
Ikeguchi M, Yamaguchi K, Kaibara N (2003) Survivin gene expression positively correlates with proliferative activity of cancer cells in esophageal cancer. Tumour Biol 24:40–45. doi:10.1159/000070659
Ito T, Shiraki K, Sugimoto K, Yamanaka T, Fujikawa K, Ito M, Takase K, Moriyama M, Kawano H, Hayashida M, Nakano T, Suzuki A (2000) Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology 31:1080–1085. doi:10.1053/he.2000.6496
Jang JS, Kim KM, Kang KH, Choi JE, Lee WK, Kim CH, Kang YM, Kam S, Kim IS, Jun JE, Jung TH, Park JY (2008) Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer 60(1):31–39
Ke X, Collins A, Ye S (2001) PIRA PCR designer for restriction analysis of single nucleotide polymorphisms. Bioinformatics 17:838–839. doi:10.1093/bioinformatics/17.9.838
Li F, Altieri DC (1999) Transcriptional analysis of human survivin gene expression. Biochem J 344(Pt 2):305–311. doi:10.1042/0264-6021:3440305
McCabe ML, Dlamini Z (2005) The molecular mechanisms of oesophageal cancer. Int Immunopharmacol 5:1113–1130. doi:10.1016/j.intimp.2004.11.017
Pickens A, Orringer MB (2003) Geographical distribution and racial disparity in esophageal cancer. Ann Thorac Surg 76:S1367–S1369. doi:10.1016/S0003-4975(03)01202-5
Salz W, Eisenberg D, Plescia J, Garlick DS, Weiss RM, Wu XR, Sun TT, Altieri DC (2005) A survivin gene signature predicts aggressive tumor behavior. Cancer Res 65:3531–3534. doi:10.1158/0008-5472.CAN-04-4284
Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ (2001) Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas. Ann Surg Oncol 8:305–310. doi:10.1007/s10434-001-0305-0
Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98. doi:10.1038/sj.cr.7290286
Stephens M, Scheet P (2005) Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 76:449–462. doi:10.1086/428594
Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989. doi:10.1086/319501
Ugur VI, Kara SP, Kucukplakci B, Demirkasimoglu T, Misirlioglu C, Ozgen A, Elgin Y, Sanri E, Altundag K, Ozdamar N (2008) Clinical characteristics and outcome of patients with stage III esophageal carcinoma: a single-center experience from Turkey. Med Oncol 25:63–68. doi:10.1007/s12032-007-0043-7
Wagner M, Schmelz K, Dorken B, Tamm I (2008) Epigenetic and genetic analysis of the survivin promoter in acute myeloid leukemia. Leuk Res 32(7):1054–1060
Xu Y, Fang F, Ludewig G, Jones G, Jones D (2004) A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells. DNA Cell Biol 23:527–537
Yamamoto T, Tanigawa N (2001) The role of survivin as a new target of diagnosis and treatment in human cancer. Med Electron Microsc 34:207–212. doi:10.1007/s007950100017
Yang L, Parkin DM, Li L, Chen Y (2003) Time trends in cancer mortality in China: 1987–1999. Int J Cancer 106:771–783. doi:10.1002/ijc.11300
Acknowledgment
This work was supported by the National Natural Science Foundation of China (No. 30872549) and Natural Science Foundation Project of CQ CSTC.
Conflict of interest statement
We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. We have full control of all primary data and that we agree that the Journal of Cancer Research and Clinical Oncology can review our data if requested.
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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 135, 1341–1349 (2009). https://doi.org/10.1007/s00432-009-0575-7
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DOI: https://doi.org/10.1007/s00432-009-0575-7