Abstract
Background and Aim
Survivin is an upregulated inhibitor of apoptosis protein in esophageal cancer (EC), and a promoter region polymorphism (−31G>C) in the survivin gene has been reported as a modulator of gene expression. We aim to explore the role of survivin −31G>C polymorphism in susceptibility and survival of EC patients in northern Indian population.
Materials and Methods
A case–control study was performed in 500 subjects (250 EC patients and 250 controls), and genotyping was done by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method.
Results
Survivin CC genotype was found to be significantly associated with EC susceptibility [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.27–4.14; P = 0.006], particularly in males (OR = 4.91; 95% CI = 2.19–11.02; P = 0.0001) having squamous cell carcinoma (SCC) histopathology (OR = 2.4; 95% CI = 1.36–4.21; P = 0.002) at middle third esophagus location (OR = 2.60; 95% CI = 1.40–4.82; P = 0.002). Patients carrying CC genotype were found to have higher susceptibility to lymph node metastasis (OR = 2.82; 95% CI = 1.46–5.48; P = 0.002). However, on survival analysis, no prognostic role of survivin −31G>C polymorphism was detected. In case-only analysis, no gene–environment interaction was observed.
Conclusion
Survivin promoter region polymorphism (−31G>C) is associated with susceptibility and clinical characteristics but not prognosis of esophageal cancer in northern Indian population.
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References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.
Umar SB, Fleischer DE. Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract Gastroenterol Hepatol. 2008;5:517–26.
Vallbohmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Dis Esophagus. 2006;19:425–32.
Knauer SK, Mann W, Stauber RH. Survivin’s dual role: an export’s view. Cell Cycle. 2007;6:518–21.
Ambrosini G, Adida C, Sirugo G, Altieri DC. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem. 1998;273:11177–82.
Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene. 2003;22:8581–89.
O’Connor DS, Schechner JS, Adida C, et al. Control of apoptosis during angiogenesis by survivin expression in endothelial cells. Am J Pathol. 2000;156:393–8.
Johnson ME, Howerth EW. Survivin: a bifunctional inhibitor of apoptosis protein. Vet Pathol. 2004;41:599–607.
Grossman D, McNiff JM, Li F, Altieri DC. Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. J Invest Dermatol. 1999;113:1076–81.
Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet. 1999;23:387–8.
Nemoto T, Kitagawa M, Hasegawa M, et al. Expression of IAP family proteins in esophageal cancer. Exp Mol Pathol. 2004;76:253–9.
Kato J, Kuwabara Y, Mitani M, et al. Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer. 2001;95:92–5.
Zhu HX, Wang YH, Zhou CQ, et al. [Expression of survivin and its significance in esophageal cancer]. Zhonghua Zhong Liu Za Zhi. 2005;27:22–4.
Sato F, Abraham JM, Yin J, et al. Polo-like kinase and survivin are esophageal tumor-specific promoters. Biochem Biophys Res Commun. 2006;342:465–71.
Martinez A, Bellosillo B, Bosch F, et al. Nuclear survivin expression in mantle cell lymphoma is associated with cell proliferation and survival. Am J Pathol. 2004;164:501–10.
Takai N, Miyazaki T, Nishida M, Nasu K, Miyakawa I. Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma. Cancer Lett. 2002;184:105–16.
Wurl P, Kappler M, Meye A, et al. Co-expression of survivin and TERT and risk of tumour-related death in patients with soft-tissue sarcoma. Lancet. 2002;359:943–5.
Cao M, Yie SM, Wu SM, et al. Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance. Clin Exp Metastasis. 2009;26:751–8.
Rosato A, Pivetta M, Parenti A, et al. Survivin in esophageal cancer: an accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma. Int J Cancer. 2006;119:1717–22.
Wang Y, Zhu H, Quan L, et al. Downregulation of survivin by RNAi inhibits the growth of esophageal carcinoma cells. Cancer Biol Ther. 2005;4:974–8.
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;23:527–37.
Jang JS, Kim KM, Kang KH, et al. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer. 2008;60:31–9.
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;135:1341–9.
Gazouli M, Tzanakis N, Rallis G, et al. Survivin −31G/C promoter polymorphism and sporadic colorectal cancer. Int J Colorectal Dis. 2009;24:145–50.
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;2:289–99.
Wang YH, Chiou HY, Lin CT, Hsieh HY, Wu CC, Hsu CD, et al. Association between survivin gene promoter −31 C/G polymorphism and urothelial carcinoma risk in Taiwanese population. Urology. 2009;73:670–4.
Cheng ZJ, Hu LH, Huang SJ. [Correlation of −31G/C polymorphisms of survivin promoter to tumorigenesis of gastric carcinoma]. Ai Zheng. 2008;27:258–63.
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;54:1021–8.
Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case–control study. Hum Immunol. 2008;69:179–86.
Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Association of interleukin-6 (-174G>C) promoter polymorphism with risk of squamous cell esophageal cancer and tumor location: an exploratory study. Clin Immunol. 2008;128:199–204.
Jain M, Kumar S, Lal P, Tiwari A, Ghoshal UC, Mittal B. Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population. Cancer Invest. 2007;25:340–6.
Jain M, Kumar S, Upadhyay R, Lal P, Tiwari A, Ghoshal UC, et al. Influence of apoptosis (BCL2, FAS), cell cycle (CCND1) and growth factor (EGF, EGFR) genetic polymorphisms on survival outcome: an exploratory study in squamous cell esophageal cancer. Cancer Biol Ther. 2007;6:1553–8.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
Borbely AA, Murvai M, Szarka K, Konya J, Gergely L, Hernadi Z, et al. Survivin promoter polymorphism and cervical carcinogenesis. J Clin Pathol. 2007;60:303–6.
Gauderman WJ aMJ. QUANTO 1.1. A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydrauscedu/gxe (2006).
Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N. Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004;96:434–42.
Jain M, Kumar S, Lal P, Tiwari A, Ghoshal UC, Mittal B. Role of GSTM3 polymorphism in the risk of developing esophageal cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:178–81.
Altieri DC, Marchisio PC. Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest. 1999;79:1327–33.
Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8:61–70.
Yang X, Xiong G, Chen X, et al. Survivin expression in esophageal cancer: correlation with p53 mutations and promoter polymorphism. Dis Esophagus. 2009;22:223–30.
Ikeguchi M, Kaibara N. Survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer. 2002;87:883–7.
Konturek PC, Kania J, Kukharsky V, Ocker S, Hahn EG, Konturek SJ. Influence of gastrin on the expression of cyclooxygenase-2, hepatocyte growth factor and apoptosis-related proteins in gastric epithelial cells. J Physiol Pharmacol. 2003;54:17–32.
Wagner M, Schmelz K, Dorken B, Tamm I. Epigenetic and genetic analysis of the survivin promoter in acute myeloid leukemia. Leuk Res. 2008;32:1054–60.
Acknowledgment
The Indian Council of Medical Research (ICMR), New Delhi, India is gratefully acknowledged for providing research and fellowship grants.
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There is no potential conflict of interest among the authors for the publication of this manuscript.
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Upadhyay, R., Khurana, R., Kumar, S. et al. Role of Survivin Gene Promoter Polymorphism (−31G>C) in Susceptibility and Survival of Esophageal Cancer in Northern India. Ann Surg Oncol 18, 880–887 (2011). https://doi.org/10.1245/s10434-010-1371-y
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DOI: https://doi.org/10.1245/s10434-010-1371-y