Skip to main content

Advertisement

SpringerLink
Log in

Role of Survivin Gene Promoter Polymorphism (−31G>C) in Susceptibility and Survival of Esophageal Cancer in Northern India

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Umar SB, Fleischer DE. Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract Gastroenterol Hepatol. 2008;5:517–26.

    Article  Google Scholar 

  3. Vallbohmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Dis Esophagus. 2006;19:425–32.

    Article  PubMed  CAS  Google Scholar 

  4. Knauer SK, Mann W, Stauber RH. Survivin’s dual role: an export’s view. Cell Cycle. 2007;6:518–21.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene. 2003;22:8581–89.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. Johnson ME, Howerth EW. Survivin: a bifunctional inhibitor of apoptosis protein. Vet Pathol. 2004;41:599–607.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet. 1999;23:387–8.

    Article  PubMed  CAS  Google Scholar 

  11. Nemoto T, Kitagawa M, Hasegawa M, et al. Expression of IAP family proteins in esophageal cancer. Exp Mol Pathol. 2004;76:253–9.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. 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.

    Article  PubMed  CAS  Google Scholar 

  33. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. Gauderman WJ aMJ. QUANTO 1.1. A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydrauscedu/gxe (2006).

  36. 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.

    Article  PubMed  Google Scholar 

  37. 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.

    Article  PubMed  CAS  Google Scholar 

  38. Altieri DC, Marchisio PC. Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest. 1999;79:1327–33.

    PubMed  CAS  Google Scholar 

  39. Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8:61–70.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  Google Scholar 

  41. Ikeguchi M, Kaibara N. Survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer. 2002;87:883–7.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    PubMed  CAS  Google Scholar 

  43. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The Indian Council of Medical Research (ICMR), New Delhi, India is gratefully acknowledged for providing research and fellowship grants.

Conflicts of interest

There is no potential conflict of interest among the authors for the publication of this manuscript.

Author information

Authors and Affiliations

  1. Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Rohit Upadhyay MSc & Balraj Mittal PhD

  2. Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Rohini Khurana MD & Shaleen Kumar MD

  3. Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

    Uday Chand Ghoshal DM

Authors
  1. Rohit Upadhyay MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rohini Khurana MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaleen Kumar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uday Chand Ghoshal DM
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Balraj Mittal PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Balraj Mittal PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-010-1371-y

Keywords

Search

Navigation